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      "body": "Safety and efficacy of Seladelpar in treatment of patients with Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis\nAbstract\nIntroduction\nPrimary Biliary Cholangitis (PBC) necessitates effective therapeutic interventions due to its potential for liver failure if untreated. Seladelpar, a selective peroxisome proliferator-activated receptor delta (PPAR-δ) agonist, has emerged as a potential therapeutic agent for PBC, showing promising improvements in biochemical markers and symptom management. However, the safety and efficacy of Seladelpar in PBC treatment remain incompletely understood. This study aims to comprehensively evaluate the safety and efficacy of Seladelpar in the treatment of patients with Primary Biliary Cholangitis through a systematic review and meta-analysis.\nMethods\nWe conducted a systematic review and meta-analysis following PRISMA guidelines. PubMed, Scopus, Cochrane Library, Science Direct, and Google Scholar were searched from inception until March 2024 for relevant studies. Randomized controlled trials comparing Seladelpar to placebo in PBC treatment were included. Primary outcomes included normalization of ALP, and secondary outcomes included biochemical response, changes in liver enzymes, and adverse events.\nResults\nThree studies comprising 496 patients were included. Seladelpar significantly normalized ALP levels (RR: 13.94, 95% CI [4.05, 47.97], p<0.0001) and demonstrated greater biochemical responses compared to placebo. It also significantly lowered ALP and ALT levels. Adverse event analysis showed no significant differences between Seladelpar and placebo. Meta-regression analysis suggested that age, sex distribution, BMI, and disease duration did not significantly influence Seladelpar's effect on ALP normalization.\nConclusions\nSeladelpar shows efficacy in improving biochemical markers and symptom management in PBC patients. Further research is needed to validate these findings and explore optimal dosing regimens. \nKeywords\nSeladelpar; Primary Biliary Cholangitis; PPAR-δ; Placebo; Meta-analysis\n\nIntroduction\nPrimary Biliary Cholangitis (PBC) represents a chronic autoimmune liver disease characterized by progressive destruction of intrahepatic bile ducts, leading to cholestasis, liver fibrosis, and potential liver failure if untreated (1–3). In recent years, the prevalence of PBC has been on the rise, most common in Europe and North America. PBC has a female predominance, affecting primarily middle-aged women (over 90% of the PBC cases), necessitating effective therapeutic interventions to mitigate its clinical impact (3,4). While Ursodeoxycholic acid (UDCA) remains the primary treatment for PBC, a significant proportion of patients exhibit inadequate response or intolerance to this standard therapy, underscoring the need for alternative treatment options (5). Seladelpar, a selective peroxisome proliferator-activated receptor delta (PPAR-δ) agonist, has emerged as a potential therapeutic agent for managing PBC (6). PPAR-δ activation has been implicated in modulating inflammatory and fibrotic processes in liver diseases, making Seladelpar an attractive candidate for PBC treatment (7). Seladelpar exhibits promising potential as a therapeutic agent for Primary Biliary Cholangitis, demonstrating significant improvements in biochemical markers of cholestasis, liver function tests, and histological features, alongside addressing safety concerns and ameliorating symptoms such as pruritus, sleep disturbances, fatigue, and serum bile acids levels in affected patients (8,9). Despite the promising findings from preliminary studies, the safety and efficacy of Seladelpar in the treatment of (PBC) remain incompletely understood, with existing literature presenting conflicting results regarding its clinical benefits. Concerns persist regarding the long-term safety profile of Seladelpar, including potential impacts on cardiovascular outcomes and other adverse effects. To address these knowledge gaps, we conducted a systematic review and meta-analysis of published literature to comprehensively evaluate Seladelpar's safety and efficacy in PBC treatment. By synthesizing data from relevant clinical trials, our study aims to provide evidence-based insights into the use of Seladelpar as a therapeutic option for PBC. Additionally, we seek to identify potential areas for future research and development, ultimately striving to improve outcomes for patients grappling with this debilitating liver disease.\nMethodology\nData Sources and Search Strategy\nThis meta-analysis was performed per the preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines (10). Databases were comprehensively searched from inception till March 2024, for potentially relevant studies, including PubMed, Scopus, Cochrane Library, Science Direct and Google scholar. The inclusive search strategy employed for each database is available in Supplementary Table 1, The bibliographies of the retrieved articles were reviewed for additional relevant articles. Additionally, grey literature sources were searched to find unpublished articles.\nStudy Selection and Eligibility Criteria\nA total of 612 articles retrieved from the systematic search were exported to the EndNote reference library, version X8.1 (Clarivate Analytics), wherein duplicates were removed. Two independent investigators (S.R and M.A) assessed all articles at the title and abstract level, after which a subsequent thorough full text review was carried out to confirm their relevance. A third investigator (A.R) was called to resolve any discrepancy. Articles fulfilling the following pre-specified eligibility criteria were included: (I) Published randomized controlled trials with no limitation of date (II) Studies that compared outcomes after receiving Seladelpar versus placebo (III) Studies that reported at least one of the outcomes of interest. All other types of studies (case series, observational studies or non-English articles) were excluded.\nData Extraction and Quality of Assessment\nThe following data were extracted from the included studies; (I) Patient baseline characteristics (II) Outcomes like Normalization of ALP, Biochemical response (biochemical response indicates any positive change or improvement in biochemical markers in response to intervention) (III) Change in direct and indirect bilirubin (IV) Any change from baseline in ALP, ALT, 5’ nucleosidase, GGT (V) Change from baseline in Total cholesterol, TG, LDL and HDL (VI) Any adverse event reported.\nTwo reviewers (M.A.N and A.A) evaluated the quality of RCTs utilizing the Cochrane Risk of Bias Tool for randomized controlled trials (ROB-2) (11). Any discrepancies were addressed through discussion and resolved by a third investigator (S.B.A).\nStatistical Analysis\nStatistical analyses were conducted using Review Manager (RevMan version 5.3; Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) by (A.R). Results were synthesized employing a random-effects model. Statistical significance was defined as a p-value ≤ 0.05. Continuous and dichotomous outcomes were utilized throughout this study, with comparisons made via mean differences, risk ratios and 95% confidence intervals (95% CI). Analysis entailed the comparison of post-intervention mean values for each outcome of interest. Heterogeneity was assessed utilizing the Higgins I² statistic, where values exceeding 50% were deemed indicative of substantial heterogeneity (12).\nResults\nStudy selection and characteristics\nA comprehensive literature search was conducted has yielded 612 articles. Upon removing duplicates and removing ineligible articles, three studies were included in this meta-analysis. The PRISMA flowchart presents the summary of the literature search (Figure 1). A total of three studies (6,13,14) comprising 496 patients (331 in Seladelpar group vs 165 in placebo group). The follow-up time ranged from 6 months up to 12 months. The mean age of patients in Seladelpar group was 55.91 years, and 55.97 years in the placebo arm.  General study characteristics and baseline characteristics of patients of the included studies is summarized in Table 1A and 1B. The details of the risk of bias assessment are given in Figures 2A, 2B and Supplementary Table 2, and all the included studies were rated as being of high quality. \nPrimary Outcome\n\nI. Normalization of ALP\n\nA meta-analysis of three studies (6,13,14) demonstrated that Seladelpar significantly normalizes levels of ALP as compared to placebo group. (RR: 13.94, 95% CI [ 4.05,47.97]; p<0.0001, I2=0%) Figure 3.\n\nSecondary outcomes\n \nI. Biochemical Response \n\nA random-effect meta-analysis was performed which included three studies (6,13,14) and demonstrated that Seladelpar was associated with greater number of biochemical responses as compared to the placebo arm. (RR: 4.18, 95% CI [ 2.74 ,6.37]; p<0.00001, I2=25%) Supplementary Figure 1\n\nII. ALP Change from baseline till longest follow-up \n\nIn the outcome of ALP change, three studies (6,13,14) were included which showed that Seladelpar was significantly associated with lowering ALP levels of patients at follow-up as compared to the patients in the placebo group. (MD: -2.06, 95% CI [ -2.87, -1.25]; p<0.00001, I2=84%) Supplementary Figure 2A\n\nAssessment of Heterogeneity \nIn order to find the cause of high heterogeneity in the plot of ALP change, we performed sensitivity analysis by excluding the outlier studies, Jones et al. 2017 (6) after which the value of I2 dropped from 84% to 0% and the results remained significant. (MD: -1.32, 95% CI [ -1.59, -1.05]; p<0.00001, I2=0%) Supplementary Figure 2B\n\nIII. ALT Change from baseline till longest follow-up \n\nFor the outcome of ALT change, three studies (6,13,14) were included in this outcome. The pooled result showed that Seladelpar was significantly associated with lowering the levels of ALT when compared to the patients of the placebo group. (MD: -0.55, 95% CI [ -0.80, -0.30]; p<0.0001, I2=0%) Supplementary Figure 3\n\nIV. Adverse events \n\nA total of three studies (6,13,14) reported adverse events and serious events. For the adverse events, the pooled result was found to be statistically insignificant (RR: 0.94, 95% CI [ 0.83, 1.07]; p=0.33, I2=40%). Similarly, the results for serious adverse events was also insignificant (RR: 0.91, 95% CI [ 0.39, 2.14]; p=0.83, I2=0%) Supplementary Figure 4\n\nV. Total complications\n\nThree studies (6,13,14) reported complication and pooled results showed that there was no significant difference in total complications between the patients in Seladelpar and placebo group. The overall results were statistically insignificant (RR: 1.14, 95% CI [0.79, 1.66]; p= 0.48; I2=56%), however, events of abdominal pain and headache were significantly greater in Seladelpar group, whereas events of pruritis were significantly more in placebo group. Supplementary Figure 5\n\nMeta regression\n\nWe examined various factors, including average age, percentage of female participants, body mass index (BMI), and the duration of the disease, to explore their potential role as covariates influencing the effect size on our primary outcome—the normalization of ALP. The results indicated that none of these covariates demonstrated a statistically significant association with the normalization of ALP. The results are as follows: average age, coeff: 0.0599, p=0.9410; female sex % coeff: 0.0969, p=0.8251; BMI coeff: 0.2400, p=0.7838; duration of disease, coeff: 0.2535, p=0.8071. (Supplementary Figures 6A-6D)\n\nDiscussion  \n\nWe conducted a meta-analysis on the safety and efficacy of Seladelpar in treating patients with primary biliary cholangitis. The purpose of publishing this data stems from the emergence of newer studies demonstrating promising results. Our analysis included three randomized controlled trials (RCTs) comparing the effects of Seladelpar in PBC patients (6,13,14). Our summary of results outlined the differences between the two groups across various primary and secondary outcomes. Our primary outcome focused on the normalization of ALP, while secondary outcomes included biochemical responses, changes in ALP and ALT levels from baseline to follow-up, and adverse effects categorized as normal adverse effects, serious adverse effects, and total complications. While the results for our primary and some secondary outcomes were significant, two outcomes did not show significance. Our study demonstrated significant improvements in ALP levels with Seladelpar treatment. However, significant heterogeneity across studies was noted, attributed to variations in parameters like dosages, sample sizes, and follow-up durations. Through sensitivity analysis, one study was identified as a significant contributor to this heterogeneity. We also observed a significant reduction in ALT levels, and our study favored Seladelpar in terms of biochemical responses. Regarding safety, Seladelpar was not associated with simple or serious adverse events, although evidence for this was moderate as it did not reach statistical significance.  \nSeladelpar, a PPAR agonist, has emerged as a recent addition to the treatment arsenal for primary biliary cholangitis (PBC) for several compelling reasons. Before its introduction, various treatment strategies had been employed, but over time, the efficacy of these drugs waned or their adverse effects became prohibitive. Ursodeoxycholic acid (UDCA), the cornerstone of PBC treatment, is hailed as highly effective. However, in a significant subset of individuals, up to 40%, UDCA fails to elicit the desired biochemical response (15). Additionally, while UDCA remains a mainstay, its efficacy diminishes in some patients over time. Obeticholic acid (OCA), another drug used in PBC management, initially showed promise by reducing enzymatic levels. Unfortunately, its use has been associated with liver damage and the potential for liver failure, limiting its widespread adoption (16,17). These challenges underscored the need for novel therapeutic approaches, leading to the introduction of seladelpar. Seladelpar offers a solution to these issues by providing a promising alternative. With its unique mechanism of action and potentially favorable safety profile, seladelpar presents an opportunity to address the limitations of previous treatments and improve outcomes for individuals with PBC (18). Several studies have underscored Seladelpar's beneficial effects in improving liver function, reducing enzyme levels, and enhancing cholestatic liver functions (15,19,20). Furthermore, Seladelpar has been shown to act as an anti-inflammatory and anti-fibrotic agent in the liver (21). It has been proposed as a potential alternative in cases where Ursodeoxycholic acid fails to yield satisfactory results (22). Seladelpar has also exhibited promise in relieving pruritus symptoms and enhancing sleep quality (8,9). In terms of biochemical response, various studies have reported positive outcomes. For example, one study demonstrated a reduction in ALP levels similar to our findings, but it also suggested a potential increase in ALT levels, which contradicted our results (6) Furthermore, because Seladelpar stimulates fatty acid desaturation pathways, the downregulation of CYP 7A1 does not lead to unfavorable alterations in lipid profiles, which is a concern with OCA (23). The effects of different Seladelpar doses on various outcomes are still being investigated. Currently, there's insufficient evidence to suggest that dose adjustments significantly impact the drug's safety and efficacy. Although one study showed varying effects on the side effect profile based on different doses, with lower doses associated with reduced adverse effects and no serious adverse effects observed at the lowest dose (24), this study was discontinued prematurely, warranting further investigation in this area. Recent clinical trials in phase 3 and phase 2 reported no significant adverse effects of the drug, highlighting its potential safety profile (25,26). However, concerns regarding the long-term safety profile of Seladelpar persist, particularly when considering it as a long-term treatment option for PBC. One study suggested that longer use of Seladelpar did not lead to an increase in adverse effects over two years, with some patients experiencing a decrease in various side effects, although one patient had a serious adverse effect (24). To increase the reliability of these findings, future studies should focus on evaluating Seladelpar's safety profile over extended periods. In our analysis, we aimed to minimize heterogeneity by focusing on the drug's efficacy while acknowledging the importance of assessing its safety profile. Therefore, our results regarding Seladelpar's efficacy in improving ALP levels were presented independently of dosage recommendations. To enhance the assessment of our main result, we conducted a meta-regression analysis to investigate potential relationships between various variables that may impact Seladelpar's effect on ALP level normalization. our findings suggested that Seladelpar functions independently of certain variables such as BMI, average age, percentage of female participants, and length of disease.  \n\nLimitations  \n\nWhile this meta-analysis provides valuable insights, it's essential to acknowledge several limitations. Firstly, the limited availability of newer studies resulted in a small sample size, potentially compromising the reliability and accuracy of our findings. Secondly, insufficient data prevented us from considering pre-existing medical conditions that may affect the drug's efficacy and safety. Thirdly, we couldn't assess the impact of different dosage regimens on the drug's effectiveness or safety. Further research is necessary to establish the optimal dosing regimen and ensure the safety and efficacy of Seladelpar in the treatment of PBC. Lastly, we couldn't explore potential interactions between the drug and pre-treatment medications, which could influence its efficacy.  \n\nConclusions  \n\nOur study findings indicate that administering Seladelpar to treat primary biliary cholangitis results in a significant reduction in ALP levels and ALT levels and an overall improvement in the patient's biochemical profile. We observed a favorable safety profile with minimum complications, which suggests that Seladelpar is an effective treatment option for primary biliary cholangitis. However, our confidence in these results is tempered by the small sample size and limited number of studies that support our conclusions. Therefore, we strongly recommend further research with larger and more diverse sample sizes, exploring different doses and combinations, and considering various comorbidities. Such research would enhance the applicability of the results and provide a comprehensive understanding of the benefits of Seladelpar in managing primary biliary cholangitis. \n\nDeclarations\nEthics Approval and Consent to Participate\nNot Applicable\nConsent for Publication\nNot Applicable\nAvailability of Data and Materials Statement\nThe dataset supporting the conclusions of this article are included in this article.\nDeclaration of Competing Interest\nThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\nFunding\nThe authors received no extramural funding for the study.\nAuthors' contributions \nAll authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work\nAcknowledgments\nNone\n\nReferences\n\n1.\tRigopoulou EI. 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ASBMB [Internet]. 2022 [cited 2024 Mar 10]; Available from: https://www.jbc.org/article/S0021-9258(22)00496-3/abstract\n22.\tLin W, Wang J, Reviews YLS, 2024 undefined. Optimal drug regimens for improving ALP biochemical levels in patients with primary biliary cholangitis refractory to UDCA: a systematic review and Bayesian network. SpringerW Lin, J Wang, Y LiuSystematic Reviews, 2024•Springer [Internet]. 2024 Dec 1 [cited 2024 Mar 10];13(1). Available from: https://link.springer.com/article/10.1186/s13643-024-02460-0\n23.\tDubois V, Eeckhoute J, … PLTJ of clinical, 2017 undefined. Distinct but complementary contributions of PPAR isotypes to energy homeostasis. Am Soc Clin InvestigV Dubois, J Eeckhoute, P Lefebvre, B StaelsThe Journal of clinical investigation, 2017•Am Soc Clin Investig [Internet]. 2017 [cited 2024 Mar 10]; Available from: https://www.jci.org/articles/view/88894\n24.\tMayo MJ, Vierling JM, Bowlus CL, Hirschfield GM, Borg BB, Harrison SA, et al. Open‐label, clinical trial extension: Two‐year safety and efficacy results of seladelpar in patients with primary biliary cholangitis. Wiley Online LibraryMJ Mayo, JM Vierling, CL Bowlus, C Levy, GM Hirschfield, GW Neff, MR GalambosAlimentary Pharmacology & Therapeutics, 2024•Wiley Online Library [Internet]. 2023 Jan 1 [cited 2024 Mar 10];59(2):186–200. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/apt.17755\n25.\tSeladelpar Reduces Cholestasis, Liver Injury and Improves Pruritus in Phase 3 [Internet]. [cited 2024 Mar 10]. Available from: https://www.rarediseaseadvisor.com/reports/seladelpar-reduces-cholestasis-liver-injury-improves-pruritus-phase-3-trial/\n26.\tBowlus CL, Galambos MR, Aspinall RJ, Hirschfield GM, Jones DEJ, Dörffel Y, et al. A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis. J Hepatol. 2022 Aug 1;77(2):353–64. \n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nTable and Figure Appendix\n\nTable 1A. General Characteristics of Included Studies Table\n\nStudy ID\tClinical trial no\tStudy Design\tStudy Duration\tCountry\tDose of Seladelpar\tSample Size (n)\tFollow up Visit\tOutcomes Measure\n\t\t\t\t\t\tSeladelpar\tPlacebo\t\t\nJones et al. 2017 \tNCT02609048 \tMulticentre, double-blind, randomised, placebo-controlled, parallel, dose-ranging trial\tNov 4, 2015, and May 26, 2016 (18 weeks)\t29 sites in North America and Europe\t50mg\t13\t13\t2 weeks\tPrimary outcome: Change in alkaline phosphatase levels over 12 weeks. Secondary outcomes encompass safety, tolerability, liver enzyme levels (AST, ALT, GGT), lipid profile, pruritus assessment, and exploratory measures including bile acid levels, inflammatory markers, and trough plasma concentrations of seladelpar and its metabolites at weeks 4 and 12.\n\t\t\t\t\t200mg\t12\t13\t\t\nHirschfield et al. 2023\tNCT03602560\tPhase 3, double-blind, randomized, placebo-controlled study\tNovember 26, 2018, and November 12, 2019\t111 sites in 21 countries\t5mg orally\t89\t87\t4 weeks\tPrimary outcomes: Composite biochemical response, ALP change from baseline, and total bilirubin after month 3. secondary endpoints: ALP normalization and change in pruritus NRS from baseline at month 3.\n\t\t\t\t\t10mg orally\t89\t87\t\t\nHirschfield et al. 2024 \tNCT04620733\tPhase 3, multicenter, double-blind, randomized, placebo-controlled trial\tUp to 12 months\t90 sites in 24 countries\t10 mg daily\t128\t65\t2 weeks\tPrimary outcomes; biochemical response and total billirubin levels at 12 months. Secondary outcomes: Normalization of alkaline phosphatase level and change in pruritis\nNCT: National Clinical Trial; mg: milligram;\t\t\n\n\nTable 1B. Patient Baseline Characteristics Table\nStudy ID\tMale/Female\tAge (Mean, SD)\tBMI (kg/m2)\tALP Level U/L (Mean, SD)\tTotal bilirubin level/ mg/Dl (Mean, SD)\tPruritis NRS score (Mean, SD)\n\tSeladelpar\tPlacebo\tSeladelpar\tPlacebo\tSeladelpar\tPlacebo\tSeladelpar\tPlacebo\tSeladelpar\tPlacebo\tSeladelpar\tPlacebo\nJones et al. 2017 \t1:12\t1:12\t54±7.47\t55±10.79\t24±5\t28±6\t312±95\t233±73\t0·73±0·27\t0·68±0·35\t-\t-\n\t0:12\t\t58.67±9.22\t\t27±4\t\t248±89\t\t0·75±0·38\t\t-\t\nHirschfield et al. 2023\t-\t-\t54.7±9.7\t55.9±8.2\t27.7±6.1\t28.2±5.5\t290.5±104.2\t293.4±106.2\t0.76±0.35\t0.71±0.32\t2.8±2.5\t2.9±2.5\n\t\t\t55.6±9.1\t\t27.6±5.9\t\t290.8±109.1\t\t0.72±0.32\t\t2.7±2.6\t\nHirschfield et al. 2024 \t-\t-\t56.6±10.0\t57.0±9.2\t-\t-\t314.6±123.0\t313.8±117.7\t0.77±0.3\t0.74±0.3\t3.0±2.8\t3.0±3.0\nALT; Alkaline phosphatase; SD: Standard deviation\t\t\t\t\t\t\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nFigure 1. PRISMA Flow Chart\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nFigure 2A. Risk of Bias Graph\n\n \n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nFigure 2B. Risk of Bias Summary\n\n \n\nFigure 3. Forest Plot of Normalization of ALP",
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      "body": "<div class=\"text-justify\">\n\n\nGreetings, Steemians! I hope you're all having fun, and I'm back with my journal after a lengthy absence.\n\nSo today is a really memorable day for me because my dearest friend's birthday is January 19th. There are a few people in my life that are really important to me, and she is one of them. So far, I've been waiting since the beginning of 2022.\n\n\n\n\n<center>![title.jpeg](https://cdn.steemitimages.com/DQmbBwEzxZMWYH68xE4xpKxd5aG1LB2wU5EC3zESWQjzEST/title.jpeg)</center>\n\n\n\n\n-------\n\n\n\nSo it all began on the evening of the 18th when all of our friends agreed to wish her at 12 a.m. in order to surprise her in a big way. I did my part and wrote her a modest wish. After that, I went to sleep and in the morning, all I could think about was her gifts because she doesn't like a lot of things, but I knew she liked the food, especially dessert.\n\n\n![ss.jpeg](https://cdn.steemitimages.com/DQmQFNzNtLnr8SHr5QTcWw4Li9tFyZjoySBaCFjreDGwds8/ss.jpeg)\n\n\n![1.1.jpeg](https://cdn.steemitimages.com/DQmX39tYFdyLSm2RVNGjEFm4mYAwQYnyYbBbW8P46Nu7L7F/1.1.jpeg)\n\n\n![1.jpeg](https://cdn.steemitimages.com/DQmcoPa3bnhMoSu9MbM2Gg7onf6vvKUZu6wrgMRohgNqPgF/1.jpeg)\n\n![2.jpeg](https://cdn.steemitimages.com/DQmbFpuL355huRDxYf5iZ8WYCFwXJCD6Pr3gMSUxCrUjPLe/2.jpeg)\n\n\n\n\n------\n\nThis piqued my interest, so I went out and got a box of beautiful roses for her, packaged it, and drove over to her house to deliver it. I had to do it quickly because I needed to prepare myself for a treat she was going to offer me later that evening.\n\nI left for the agreed-upon location at 5:30 p.m., after having a bath, where she had brought numerous acquaintances.\nWe enjoyed ice cream, kababs, and other treats there.\n\n\n\n\n![3.jpeg](https://cdn.steemitimages.com/DQmXFtTKZHMdP8WFuuPkim2DEunZknv5h5ckVWue6EXdujL/3.jpeg)\n\n![4.jpeg](https://cdn.steemitimages.com/DQmXFPPPsmqKP3CpAEtmA64keb8M9CHNkSS5ZSibAqvRg92/4.jpeg)\n\n![5.jpeg](https://cdn.steemitimages.com/DQmdFun1RTeYHzW2oY9PYt3EJcZDq6GapqULntk78N75KWQ/5.jpeg)\n\n![6.jpeg](https://cdn.steemitimages.com/DQmRXBjrow3Rwm8FWhYznChjFXVoXhdCKuqDvK6YeJpyBp5/6.jpeg)\n\n![7.jpeg](https://cdn.steemitimages.com/DQmTo8MxQw7RWu4wN3Pxw35g3P3Pq8BmhRbyE16yk74thQ8/7.jpeg)\n\n\n\n-------\n\nIt's quite reflective to spend time with old pals. We had a great time and then returned to our own homes.\n\nSo here is my diary; if you find it interesting, please share your thoughts in the comments section.\n\nThank You\n\n------\n\ncc;\n@steemit-pak\n@haidermehdi\n@hassanabid\n@vvarishayy\n\n\n\n------\n\nregards,\n@hamzaali01</div>",
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      "body": "<div class=\"text-justify\">\n\n\nI hope you are all doing well and enjoying life as normal, thanks to ALLAH almighty's grace.\n\n\n\nToday, I'm going to share a diary of how I utilize technology in my daily life.  \n\n\n\n\nWhen I get up in the morning, I recite the Fajr prayer, then take a shower and freshen up before checking my phone. I opened my phone and looked at the notification panel; there were a lot of them, and my phone was getting hung up, so I increased the volume.\n\n\n\n![1.jpeg](https://cdn.steemitimages.com/DQmbWqR2Y9ndZ7qHe4jKffwtC5jPf2jUk3pz7aGbm7nhQah/1.jpeg)\n\n----\n\nI opened my Whatsapp and answered the messages that had been sent to me.\n\n\n![2.jpeg](https://cdn.steemitimages.com/DQmWsvRJ4okCFQC7ZEMJkg2BTUZU8M8T4mRM5MJfdFNn7B1/2.jpeg)\n\n-------\n\n\nI went onto Facebook and scrolled for a few minutes. Then I remembered that a friend had recently urged me to join \"THE JOURNEY CLUB,\" a Facebook club.\n\n![3 good.jpeg](https://cdn.steemitimages.com/DQmZpKkKVQV1nxPM83E5JtTL3QLHjbiFuYt7WkKySdRc8ZP/3%20good.jpeg)\n\n-----\n\n\nAfter that, I was preoccupied with my usual responsibilities until my mother informed me that I needed to go food shopping. Because we couldn't go outdoors because to the Corona epidemic, I used contemporary technology and ordered everything from home.\n\n![4.jpeg](https://cdn.steemitimages.com/DQmQuCAnpCp3Q33RdDE21tBGkPdWPGbie7x3Gb4EM57CFrS/4.jpeg)\n\n![5.jpeg](https://cdn.steemitimages.com/DQmZedEMbZnJEN2E8WueSaFj6ksvc2GqSXf51sJnY1YVz8a/5.jpeg)\n\n-------\n\n\nI used to spend my free time playing a popular adolescent game. The game's name is PUBG Mobile. We've heard a lot of stories of people being addicted to it, but I just play it when I have free time throughout my busy schedule.\n\n\n![6.jpeg](https://cdn.steemitimages.com/DQmTnpNnPZCNobYG9Vq9H36pNVz9dBcTADQdofKgAiASaAM/6.jpeg)\n\n![7.jpeg](https://cdn.steemitimages.com/DQmTyLnfjwFFsFFvQQCHC5DKvwyCGbemTZaehgqqovNGFdm/7.jpeg)\n\n---\n\nSo that's it for today. I'll come again soon with a new day and a new diary game\n\nThank You\n\n------\n\ncc;\n@cryptokraze\n@siz-official\n\n-----\n\nregards,\n@hamzaali01</div>",
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      "body": "<div class=\"text-justify\">\n\n\nTo all the people, reading this post Asalam o Alyikum. How are you all? I am fine and I hope you all are fine too.\n\n\n\n<center>![title.jpeg](https://cdn.steemitimages.com/DQmWf39iBG6k9EPkjufwbriSzjjomioTxUJLnyXTKtPhRHE/title.jpeg)</center>\n\n\n-----\n\nSo I came again with a thrilling diary of a day spent in Lahore .it was as nice as it is always but that day I was feeling a completely different environment as I am not very much habitual of using guest rooms and first time in my life I was alone in a distinct city without my kith and kins.it started when I woke up so late as it was 11:30 am and because of the very cold temperature, I could not get out of my bed. after refreshing myself I got my breakfast which was entirely different I usually take paratha and omelet as breakfast but there it was a small bun with a cup of tea that was very insufficient for me.\n\n\n\n\n![1.jpeg](https://cdn.steemitimages.com/DQmYKABThPrY2rDVSH9xsjpG69zEZLE8HydCyXmJorVZjkC/1.jpeg)\n\n\n\n------\n\nAfter taking breakfast I left for the Azam cloth center of Lahore for which I visited Lahore. After so much extensive dealings I got some orders for my products\n\n\n![6.jpeg](https://cdn.steemitimages.com/DQmcZ8fZKaHXDAMLhoTPtHbwNHKJQrfWJoKjGfzfuq87f6j/6.jpeg)\n\n\n\n------\n\nIn these discussions time for namaz e  Zuhr clicked so I went for practicing my salah at the masjid e wazir e khan. It was so much mesmerizing moment when I saw that mosque, I generally get in love with ancient sculptures and monuments and their works so I watched that mosque without a blink I took some clicks for my diary. basically, that mosque was the remains of the Mughal emperor. Mughal emperor Shah Jahan had ordered to build that mosque.it was built in 1629 with such descent hands that they are still adoring every visitor.\n\n\n\n\n![7.jpeg](https://cdn.steemitimages.com/DQmc7ZffXbx4euc1Pa41EjfNjsC3sqKFmwjGyUCQLnewCFX/7.jpeg)\n\n![8.jpeg](https://cdn.steemitimages.com/DQmezAUStx5j18rcjoG5j7UUUUUMcC5qqSHM5gsNw7PqYnM/8.jpeg)\n\n\n![3.jpeg](https://cdn.steemitimages.com/DQmRZkdC5N2AAFfGp3j8wWAX8tngKVmi2ez74xejjnnRZCe/3.jpeg)\n\n![5.jpeg](https://cdn.steemitimages.com/DQmZzX3WwzAFNwdmjB34Hk8h1jvmtc9mAThRn9jQBXD7KSB/5.jpeg)\n\n\n\n\n--------\n\n\nAfter that, I left for the market again to collect some gifts for my friend whose birthday will be in this month. I saw some suits and after that, I purchased one from them for her.\n\n\n\n![2.jpeg](https://cdn.steemitimages.com/DQmRRryf2vvBnC3cfQK5HfPua2EPkiYZboL8S7bjMAMuLnK/2.jpeg)\n\n\n\n![4.jpeg](https://cdn.steemitimages.com/DQmXGTHbxvmE1i2GXRz4vT9sv5M6t8pARHTtLmUG5cEmDgd/4.jpeg)\n\n\n\nAfter so much wandering and exhaustive selling, I returned to my hotel again and attained video conferences from the dealers for further explanations of my product in these meetings I just forgot to have any meal but randomly took something I couldn't remember. and at 2:30 I was hugged by my couch and traveled to the destiny of relaxed slumber.\n\n\nSo that's all I've got for today. I hope you enjoyed reading my diary. I'll be back with a new journal shortly.\n\nThank you \n\n------\n\nCc;\n@steemit-pak\n@haidermehdi\n@vvarishayy\n@hassanabid\n\n\n------\n\nregards,\n@hamzaali01",
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