Real-world effectiveness of GLP-1 receptor agonist-based treatment strategies on "time in range" in patients with type 2 diabetes.

Background: Diabetes affects millions of people worldwide annually, and several methods, including medications, are used for its management; glucagon-like peptide-1 receptor agonists (GLP-1RAs) are one such class of medications. The efficacy and safety of GLP-1RAs in treating type 2 diabetes mellitus (T2DM) have been assessed and have been shown to significantly improve time in range (TIR) in several clinical trials. However, presently, there is a lack of real-world evidence on the efficacy of GLP-1RAs in improving TIR. To address this, we investigated the effect of GLP-1RA-based treatment strategies on TIR among patients with T2DM in real-world clinical practice. Methods: This multicenter, retrospective, real-world study included patients with T2DM who had previously used a continuous glucose monitoring (CGM) system and received treatment with GLP-1RAs or oral antidiabetic drugs (OADs). Patients who received OADs served as controls and were matched in a 1:1 ratio to their GLP-1RA counterparts by propensity score matching. The primary endpoint was the TIR after 3-6 months of treatment. Results: According to propensity score matching, 202 patients were equally divided between the GLP-1RA and OAD groups. After 3-6 months of treatment, the TIR values for the GLP-1RA and OAD groups were 76.0% and 65.7%, respectively (p < 0.001). The GLP-1RA group displayed significantly lower time above range (TAR) and mean glucose values than the OAD group (p < 0.001). Subgroup analysis revealed that, compared with the administration of liraglutide, the administration of semaglutide and polyethylene glycol loxenatide (PEG-Loxe) significantly improved TIR over 3-6 months of treatment (p < 0.05). Conclusion: These real-world findings indicate that GLP-1RA-based treatment strategies could be superior to oral treatment strategies for improving TIR among patients with T2DM and that once-weekly GLP-1RA may be more effective than a once-daily GLP-1RA. Clinical trial registration: http://www.chinadrugtrials.org.cn/index.html, identifier number ChiCTR2300073697.

Radiological characteristics predicting early poor drug response in patients with hemifacial spasm.

OBJECTIVES: Patients with hemifacial spasm (HFS) often resort to botulinum toxin injections or microvascular decompression surgery when medication exhibits limited effectiveness. This study aimed to identify MRI and demographic factors associated with poor drug response at an early stage in patients with HFS. METHODS: We retrospectively included patients with HFS who underwent pre-therapeutic MRI examination. The presence, location, severity, and the offending vessels of neurovascular compression were blindly evaluated using MRI. Drug responses and clinical data were obtained from the medical notes or phone follow-ups. Logistic regression analysis was performed to identify potential factors. RESULTS: A total of 116 patients were included, with an average age at the time of first examination of 50.4 years and a median duration of onset of 18 months. Forty-nine (42.2%) patients reported no symptom relief. Thirty-seven (31.9%) patients reported poor symptom relief. Twenty-two (19.0%) patients reported partial symptom relief. Eight (6.9%) patients achieved complete symptom relief. The factors that were statistically significant associated with poor drug responses were contact in the attach segment of the facial nerve and aged 70 and above, with an odds ratio of 7.772 (p = 0.002) and 0.160 (p = 0.028), respectively. CONCLUSIONS: This study revealed that mild compression in the attach segment of the facial nerve in pre-therapeutic MRI increases the risk of poor drug responses in patients with HFS, while patients aged 70 and above showed a decreased risk. These findings may assist clinician to choose optimal treatment at an early stage.

Epidemiological Analysis of Global and Regional Lung Cancer Mortality: Based on 30-Year Data Analysis of Global Burden Disease Database.

The objective of this study was to understand dynamic global and regional lung cancer fatality trends and provide a foundation for effective global lung cancer prevention and treatment strategies. Data from 1990 to 2019 were collected from the Global Burden Disease (GBD) database and statistical analysis was conducted using Excel 2010. Standardization was based on the GBD's world population structure, and the Average Annual Percentage Change (AAPC) was calculated using Joinpoint 4.8.0.1 software. Bayesian age-period-cohort analysis (BAPC) predicted global lung cancer mortality from 2020 to 2030. In 2019, worldwide lung cancer deaths reached 2,042,600, a 91.75% increase from 1990 (1,065,100). The standardized age-specific death rate in 2019 was 25.18 per 100,000. Males had a rate of 37.38 while females had 14.99. Men saw a decreasing trend while women experienced an increase. High- and medium-high-SDI regions had declining rates (-0.3 and -0.8 AAPCs) whereas middle-, low-, and low-middle-SDI regions had increased mortality rates (AAPC = 0.1, AAPC = 0.37, AAPC = 0.13). Several regions, including Oceania, South Asia, East Asia, Western Sub-Saharan Africa, Southeast Asia, and Eastern Sub-Saharan Africa, witnessed rising global lung cancer mortality rates (p < 0.01). The global standardized mortality rate for lung cancer is expected to decrease from 2020 to 2030, but predictions indicate increasing female mortality and decreasing male mortality. Despite overall declines, rising female mortality remains a concern. Effective measures are essential to reduce mortality rates and improve patients' quality of life in the global fight against lung cancer.

Evaluating the effect of food components on the digestion of dietary nucleic acids in human gastric juice in vitro.

Nucleic acids (NAs) were recently shown to be digested by pepsin in vitro; however, NAs digestion in human gastric juice in vivo is more complicated because of the complex gastric environment and ingestion of other food components. The purpose of this study was to investigate the digestibility of NAs in real human gastric juices after ingestion of other food components. As a result, DNA digestion was not affected when carbohydrates, proteins, and metal elements were ingested within the recommended dietary intake levels. Separately, protein exerted an inhibitory effect on DNA digestion when the mass ratio of protein:DNA was greater than 40:1. DNA exists in the nucleoprotein, which is closer to the state of DNA in real food, and was digested efficiently in human gastric juice. Meanwhile, DNA digestion was rarely affected even when the concentrations of monovalent ion (Na+) and divalent ions (Mg2+) were as high as 500 and 100 mM, respectively, and high concentration of Mg2+ ranged from 20 to 100 mM accelerated the digestion. In particular, short-stranded DNA (<100 nt) and miRNAs (19 ~ 25 nt) were not obviously degraded in human gastric juice. In conclusion, dietary NAs were digested efficiently and were not affected by other food components in human gastric juice, which may facilitate further digestion and utilization of DNA in the intestinal tract.

The global, regional and national burden of type 2 diabetes mellitus in the past, present and future: a systematic analysis of the Global Burden of Disease Study 2019.

Aim: To report the global, regional, and national burden of type 2 diabetes mellitus (T2DM) in 2019, assess its trends in the past, and forecast its trends in the future. Methods: The main data source was the Global Burden of Disease 2019 database. We assessed the changes in T2DM burden from 1990 to 2019 with joinpoint regression analysis. Age-period-cohort analysis was used to forecast the T2DM incidence and mortality rate from 2020 to 2034. Results: The burden of T2DM has increased from 1990 to 2019 generally. The low-middle socio-demographic index (SDI) region had the highest increase in age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years (ASDR) due to T2DM. Nationally, the increase in ASIR (r=0.151, p=0.046) and the decrease in ASMR (r=0.355, p<0.001) were positively correlated with SDIs. In 2019, the global ASIR, ASPR, ASMR, ASDR due to T2DM were 259.9 (95% UI 240.3-281.4), 5282.9 (95% UI 4853.6-5752.1), 18.5 (95% UI 17.2-19.7), and 801.5 (95% UI 55477000-79005200) per 100,000 population, respectively. Additionally, the ASIR (r=0.153, p=0.030) and ASPR (r=0.159, p=0.024) of T2DM were positively correlated with SDIs, while ASMR (r=-0.226, p=0.001) and ASDR (r=-0.171, p=0.015) due to T2DM were negatively correlated with SDIs. The ASIR was estimated to increase to 284.42, and ASMR was estimated to increase to 19.1 from 2030 to 2034, per 100,000 population. Conclusion: Globally, the burden of T2DM has increased in the past and was forecast to continue increasing. Greater investment in T2DM prevention is needed.

Offshoring or reshoring: the impact of tax regulations on operations strategies.

After decades of outsourcing to low-cost countries, companies are restructuring their production footprint globally. Especially having experienced supply chain disruption caused by the unprecedented Covid-19 pandemic for the past several years, many multinational companies are considering bringing their operations back home (i.e., reshoring). At the same time, the U.S. government proposes using tax penalties to motivate companies to reshore. In this paper, we study how a global supply chain adjusts its offshoring and reshoring production decisions under two different circumstances: (1) under traditional corporate tax regulations; (2) under the proposed tax penalty regulations. We analyze cost variants, tax structures, market access and production risks to identify conditions where global companies decide to bring manufacturing back to their domestic countries. Our results show that multinational companies would be more likely to relocate the production from the main foreign country to an alternative country that enjoys even lower production costs under the proposed tax penalty. As identified by our analysis and as well as numerical simulations, reshoring can only occur in rare situations such as when the production costs in the foreign countries are close to that in the domestic country. Besides potential national tax reform, we also discuss the impact of the Global Minimum Tax Rate proposed by the G7 on global companies' offshoring/reshoring decisions.

[Cloning and expression analysis of U6 promoters in Panax quinquefolius].

The U6 promoter is an important element driving sgRNA transcription in the CRISPR/Cas9 system. Seven PqU6 promo-ter sequences were cloned from the gDNA of Panax quinquefolium, and the transcriptional activation ability of the seven promoters was studied. In this study, seven PqU6 promoter sequences with a length of about 1 300 bp were cloned from the adventitious roots of P. quinquefolium cultivated for 5 weeks. Bioinformatics tools were used to analyze the sequence characteristics of PqU6 promoters, and the fusion expression vectors of GUS gene driven by PqU6-P were constructed. Tobacco leaves were transformed by Agrobacterium tumefaciens-mediated method for activity detection. The seven PqU6 promoters were truncated from the 5'-end to reach 283, 287, 279, 289, 295, 289, and 283 bp, respectively. The vectors for detection of promoter activity were constructed with GUS as a reported gene and used to transform P. quinquefolium callus and tobacco leaves. The results showed that seven PqU6 promoter sequences(PqU6-1P to PqU6-7P) were cloned from the gDNA of P. quinquefolium, with the length ranged from 1 246 bp to 1 308 bp. Sequence comparison results showed that the seven PqU6 promoter sequences and the AtU6-P promoter all had USE and TATA boxes, which are essential elements affecting the transcriptional activity of the U6 promoter. The results of GUS staining and enzyme activity test showed that all the seven PqU6 promoters had transcriptional activity. The PqU6-7P with a length of 1 269 bp had the highest transcriptional activity, 1.31 times that of the positive control P-35S. When the seven PqU6 promoters were truncated from the 5'-end(PqU6-1PA to PqU6-7PA), their transcriptional activities were different in tobacco leaves and P. quinquefolium callus. The transcriptional activity of PqU6-7PA promoter(283 bp) was 1.59 times that of AtU6-P promoter(292 bp) when the recipient material was P. quinquefolium callus. The findings provide more ideal endogenous U6 promoters for CRISPR/Cas9 technology in ginseng and other medicinal plants.

Efficacy of polyethylene glycol loxenatide versus insulin glargine on glycemic control in patients with type 2 diabetes: a randomized, open-label, parallel-group trial.

Objective: This trial aimed to evaluate the glycemic control of polyethylene glycol loxenatide measured with continuous glucose monitoring (CGM) in patients with type 2 diabetes mellitus (T2DM), with the hypothesis that participants given PEG-Loxe would spend more time in time-in-range (TIR) than participants were given insulin glargine after 24 weeks of treatment. Methods: This 24-week, randomized, open-label, parallel-group study was conducted in the Department of Endocrine and Metabolic Diseases, Longhu Hospital, Shantou, China. Participants with T2DM, who were ≥45 years of age, HbA1c of 7.0%-11.0%, and treated at least 3 months with metformin were randomized (1:1) to receive PEG-Loxe or insulin glargine. The primary endpoint was TIR (blood glucose range: 3.9-10.0 mmol/L) during the last 2 weeks of treatment (weeks 22-24). Results: From March 2020 to April 2022, a total of 107 participants with T2DM were screened, of whom 78 were enrolled into the trial (n = 39 per group). At the end of treatment (weeks 22-24), participants given PEG-Loxe had a greater proportion of time in TIR compared with participants given insulin glargine [estimated treatment difference (ETD) of 13.4% (95% CI, 6.8 to 20.0, p < 0.001)]. The tight TIR (3.9-7.8 mmol/L) was greater with PEG-Loxe versus insulin glargine, with an ETD of 15.6% (95% CI, 8.9 to 22.4, p < 0.001). The time above range (TAR) was significantly lower with PEG-Loxe versus insulin glargine [ETD for level 1: -10.5% (95% CI: -14.9 to -6.0), p < 0.001; ETD for level 2: -4.7% (95% CI: -7.9 to -1.5), p = 0.004]. The time below range (TBR) was similar between the two groups. The mean glucose was lower with PEG-Loxe versus insulin glargine, with an ETD of -1.2 mmol/L (95% CI, -1.9 to -0.5, p = 0.001). The SD of CGM glucose levels was 1.88 mmol/L for PEG-Loxe and 2.22 mmol/L for insulin glargine [ETD -0.34 mmol/L (95% CI: -0.55 to -0.12), p = 0.002], with a similar CV between the two groups. Conclusion: The addition of once-weekly GLP-1RA PEG-Loxe to metformin was superior to insulin glargine in improving glycemic control and glycemic variability evaluated by CGM in middle-aged and elderly patients with T2DM.

Pharmacoeconomic analysis (CER) of Dulaglutide and Liraglutide in the treatment of patients with type 2 diabetes.

Aim: To evaluate the treatment effect Fand pharmacoeconomic value of Dugaglutide in women with type 2 diabetes. Methods: Women (n=96) with type 2 diabetes recruited from June 2019 to December 2021 were randomized into two equal groups. The control group was treated with Liraglutide, and the observation group was treated with Dulaglutide, both for 24 weeks. The blood glucose levels, biochemical index, insulin resistance index (HOMA-IR), cost-effect ratio (CER), and drug safety were determined and compared between the two groups. Results: Blood glucose levels, the biochemical index, and HOMA-IR were lower in both groups after the treatment (P < 0.05), and there was no statistical difference in the blood glucose levels, biochemical index and HOMA-IR between the two groups (P > 0.05). The CER levels did not differ statistically between the two groups (P > 0.05). Both the cost and the incidence of drug side effects during solution injection were lower in the observation group than in the control group after 24 weeks of treatment (P < 0.05). Conclusion: Both Dulaglutide and Liraglutide can reduce blood glucose levels, improve biochemical index, and HOMA-IR levels in women with type 2 diabetes. Dulaglutide is more cost-effective and safe. Clinical trial registration: https://www.chictr.org.cn/index.aspx, identifier ChiCTR1900026514.

Advances in mechanism and regulation of PANoptosis: Prospects in disease treatment.

PANoptosis, a new research hotspot at the moment, is a cell death pattern in which pyroptosis, apoptosis, and necroptosis all occur in the same cell population. In essence, PANoptosis is a highly coordinated and dynamically balanced programmed inflammatory cell death pathway that combines the main features of pyroptosis, apoptosis, and necroptosis. Many variables, such as infection, injury, or self-defect, may be involved in the occurrence of PANoptosis, with the assembly and activation of the PANoptosome being the most critical. PANoptosis has been linked to the development of multiple systemic diseases in the human body, including infectious diseases, cancer, neurodegenerative diseases, and inflammatory diseases. Therefore, it is necessary to clarify the process of occurrence, the regulatory mechanism of PANoptosis, and its relation to diseases. In this paper, we summarized the differences and relations between PANoptosis and the three types of programmed cell death, and emphatically expounded molecular mechanism and regulatory patterns of PANoptosis, with the expectation of facilitating the application of PANoptosis regulation in disease treatment.

Nobiletin inhibits breast cancer cell migration and invasion by suppressing the IL-6-induced ERK-STAT and JNK-c-JUN pathways.

BACKGROUND: Breast cancer is one of the most common cancers in women, affecting more than 2 million women worldwide annually. However, effective treatments for breast cancer are limited. Nobiletin is a flavonoid present in the dried mature pericarp of mandarin orange (Citrus reticulata Blanco), which is used to prepare Citri Renetulatae Pericarpium and can inhibit tumour growth and progression according to modern pharmacological studies. However, whether nobiletin exhibits an antimetastatic role in breast cancer and its potential mechanism need to be further investigated. PURPOSE: This study aims to evaluate the inhibitory effect of nobiletin on breast cancer and to elucidate potential mechanisms against invasion and migration. METHODS: Cell viability was determined by cell counting kit-8 and colony formation assays. Wound healing and Boyden chamber assays detected cancer cell migration and invasion capabilities. Immunoblotting and qPCR were applied to determine the protein and mRNA expression levels of extracellular signal-regulated kinases (ERK) and the c-Jun N-terminal kinase (JNK) signalling pathways. Molecular docking was used to assess the degree of nobiletin binding to phosphatidylinositol 3-kinase (PI3K). Xenografts and liver metastases were constructed in BALB/c nude mice to evaluate the anticancer effect of nobiletin in vivo. H&E staining and immunohistochemistry were used to detect proliferation and the expression of related proteins. RESULTS: Nobiletin induced cell death in a concentration- and time-dependent manner and possessed anti-invasion and anti-migration effects on MCF-7 and T47D cells by suppressing the interleukin-6-induced ERK and JNK signalling pathways. In addition, nobiletin docked with the binding site of PI3K, and the binding score was -8.0 kcal/mol. Furthermore, the inhibition of breast cancer growth and metastasis by nobiletin was demonstrated by constructing xenografts and liver metastases in vivo. CONCLUSION: Nobiletin inhibited liver metastasis of breast cancer by downregulating the ERK-STAT and JNK-c-JUN pathways, and its safety and efficacy were verified, indicating the potential of nobiletin as an anticancer agent.

Early-life starvation alters lipid metabolism in adults to cause developmental pathology in Caenorhabditis elegans.

Early-life malnutrition increases adult disease risk in humans, but the causal changes in gene regulation, signaling, and metabolism are unclear. In the roundworm Caenorhabditis elegans, early-life starvation causes well-fed larvae to develop germline tumors and other gonad abnormalities as adults. Furthermore, reduced insulin/IGF signaling during larval development suppresses these starvation-induced abnormalities. How early-life starvation and insulin/IGF signaling affect adult pathology is unknown. We show that early-life starvation has pervasive effects on adult gene expression which are largely reversed by reduced insulin/IGF signaling following recovery from starvation. Early-life starvation increases adult fatty-acid synthetase fasn-1 expression in daf-2 insulin/IGF signaling receptor-dependent fashion, and fasn-1/FASN promotes starvation-induced abnormalities. Lipidomic analysis reveals increased levels of phosphatidylcholine in adults subjected to early-life starvation, and supplementation with unsaturated phosphatidylcholine during development suppresses starvation-induced abnormalities. Genetic analysis of fatty-acid desaturases reveals positive and negative effects of desaturation on development of starvation-induced abnormalities. In particular, the ω3 fatty-acid desaturase fat-1 and the Δ5 fatty-acid desaturase fat-4 inhibit and promote development of abnormalities, respectively. fat-4 is epistatic to fat-1, suggesting that arachidonic acid-containing lipids promote development of starvation-induced abnormalities, and supplementation with ARA enhanced development of abnormalities. This work shows that early-life starvation and insulin/IGF signaling converge on regulation of adult lipid metabolism, affecting stem-cell proliferation and tumor formation.

Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes: A systematic review.

There is a strong link between fecal microbiota and the development of type 1 diabetes. As an emerging therapeutic modality, fecal microbiota transplantation has been shown to be safe and effective in the treatment of many intestinal and extraintestinal diseases. Various studies have found that fecal microbiota transplantation can treat diseases by correcting patients' immune disorders. Besides, many studies have found that fecal microbiota transplantation can improve glycemic control and insulin resistance in diabetic patients. Therefore, this paper reviews the mechanism of action of fecal microbiota transplantation on autoimmune-mediated T1DM and the current research progress, feasibility, and issues that need to be addressed in the future development of fecal microbiota transplantation in the treatment of autoimmune-mediated T1DM.

Investigating the effects and mechanisms of Erchen Decoction in the treatment of colorectal cancer by network pharmacology and experimental validation.

Objective: Erchen Decoction (ECD), a well-known traditional Chinese medicine, exerts metabolism-regulatory, immunoregulation, and anti-tumor effects. However, the action and pharmacological mechanism of ECD remain largely unclear. In the present study, we explored the effects and mechanisms of ECD in the treatment of CRC using network pharmacology, molecular docking, and systematic experimental validation. Methods: The active components of ECD were obtained from the TCMSP database and the potential targets of them were annotated by the STRING database. The CRC-related targets were identified from different databases (OMIM, DisGeNet, GeneCards, and DrugBank). The interactive targets of ECD and CRC were screened and the protein-protein interaction (PPI) networks were constructed. Then, the hub interactive targets were calculated and visualized from the PPI network using the Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. In addition, the molecular docking was performed. Finally, systematic in vitro, in vivo and molecular biology experiments were performed to further explore the anti-tumor effects and underlying mechanisms of ECD in CRC. Results: A total of 116 active components and 246 targets of ECD were predicted based on the component-target network analysis. 2406 CRC-related targets were obtained from different databases and 140 intersective targets were identified between ECD and CRC. 12 hub molecules (STAT3, JUN, MAPK3, TP53, MAPK1, RELA, FOS, ESR1, IL6, MAPK14, MYC, and CDKN1A) were finally screened from PPI network. GO and KEGG pathway enrichment analyses demonstrated that the biological discrepancy was mainly focused on the tumorigenesis-, immune-, and mechanism-related pathways. Based on the experimental validation, ECD could suppress the proliferation of CRC cells by inhibiting cell cycle and promoting cell apoptosis. In addition, ECD could inhibit tumor growth in mice. Finally, the results of molecular biology experiments suggested ECD could regulate the transcriptional levels of several hub molecules during the development of CRC, including MAPKs, PPARs, TP53, and STATs. Conclusion: This study revealed the potential pharmacodynamic material basis and underlying molecular mechanisms of ECD in the treatment of CRC, providing a novel insight for us to find more effective anti-CRC drugs.

Clinical Observation of Fuzheng Xiaoji Granule in the Treatment of Stage IIIC Colorectal Cancer.

Objective: This study aimed to evaluate the effectiveness and safety of Fuzheng Xiaoji granule in patients with stage IIIC colorectal cancer. Methods: A total of 150 patients with stage IIIC colorectal cancer treated in Shanghai Ruijin Hospital from January 2019 to January 2022 were selected. They were divided into treatment and control groups according to a 2 : 1 random number table. There were 100 cases in the treatment group and 50 cases in the control group. The treatment group was administered Fuzheng Xiaoji (FZXJ) granule, and the control group was administered the placebo orally. The primary endpoint was disease-free survival (DFS). In addition, after 6 months, the changes in Traditional Chinese Medicine (TCM) symptom score (fatigue, emotional depression, chest tightness, insomnia, anorexia, abdominal distension, abdominal pain, soreness and weakness in the waist and legs, chills, and dysphoria in the chest, palm, and soles) were compared. Results: The DFS was 34.37 ± 2.91 months in the control group and 37.0 ± 1.08 months in the treatment group (p < 0.05). Compared with the control group, the treatment group showed less fatigue, abdominal distension, and soreness and weakness in the waist and legs (p < 0.05), significantly. The scores of emotional depression and anorexia decreased obviously, with a significant difference between the control and treatment groups (p < 0.01). There were no significant differences between the control and treatment groups in the incidence of chest tightness, insomnia, abdominal pain, chills, and dysphoria in the chest, palm, and soles (p > 0.05). Conclusion: Fuzheng Xiaoji granule can improve patients' symptoms and prolong the DFS.

Clinical utility of target amplicon sequencing test for rapid diagnosis of drug-resistant Mycobacterium tuberculosis from respiratory specimens.

An in-house-developed target amplicon sequencing by next-generation sequencing technology (TB-NGS) enables simultaneous detection of resistance-related mutations in Mycobacterium tuberculosis (MTB) against 8 anti-tuberculosis drug classes. In this multi-center study, we investigated the clinical utility of incorporating TB-NGS for rapid drug-resistant MTB detection in high endemic regions in southeast China. From January 2018 to November 2019, 4,047 respiratory specimens were available from patients suffering lower respiratory tract infections in Hong Kong and Guangzhou, among which 501 were TB-positive as detected by in-house IS6110-qPCR assay with diagnostic sensitivity and specificity of 97.9 and 99.2%, respectively. Preliminary resistance screening by GenoType MTBDRplus and MTBDRsl identified 25 drug-resistant specimens including 10 multidrug-resistant TB. TB-NGS was performed using MiSeq on all drug-resistant specimens alongside 67 pan-susceptible specimens, and demonstrated 100% concordance to phenotypic drug susceptibility test. All phenotypically resistant specimens with dominating resistance-related mutations exhibited a mutation frequency of over 60%. Three quasispecies were identified with mutation frequency of less than 35% among phenotypically susceptible specimens. They were well distinguished from phenotypically resistant cases and thus would not complicate TB-NGS results interpretations. This is the first large-scale study that explored the use of laboratory-developed NGS platforms for rapid TB diagnosis. By incorporating TB-NGS with our proposed diagnostic algorithm, the workflow would provide a user-friendly, cost-effective routine diagnostic solution for complicated TB cases with an average turnaround time of 6 working days. This is critical for timely management of drug resistant TB patients and expediting public health control on the emergence of drug-resistant TB.

SARS-CoV-2 vaccination in androgen sensitive phenotypes - A study on associated factors for SARS-CoV-2 vaccination and its adverse effects among androgenetic alopecia and benign prostate hyperplasia patients.

Background: Androgen sensitivity, which was established as the leading etiology of androgenetic alopecia (AGA) and benign prostatic hyperplasia (BPH), plays an important role in SARS-CoV-2 infection. Vaccination is essential for AGA and BPH patients in view of the high risk from SARS-CoV-2 infection. Purpose: We aimed to investigate the associated factors for SARS-CoV-2 vaccination and its side effects in populations with AGA and BPH. Method: We collected the data on SARS-CoV-2 vaccination and adverse reactions of male AGA and BPH patients visited the outpatient of Xiangya hospital by telephone and web-based questionnaires. Vaccination rate and adverse reactions were compared by different vaccine types and use of anti-androgen therapy. Result: A total of 457 AGA patients and 397 BPH patients were recruited in this study. Among which, 92.8% AGA patients and 61.0% BPH patients had at least the first dose of SARS-CoV-2 vaccination (p < 0.001). Having comorbidities and use of anti-androgen therapy increased the risk of un-vaccination among AGA by 2.875 and 3.729 times, respectively (p < 0.001). Around 31.1% AGA patients and 9.5% BPH patients presented adverse reactions, which were mostly mild. Anti-androgen therapy increased the inclination of injection site pain after vaccination (18.7% vs 11.9%; OR: 1.708, 95% CI: 1.088-2.683, p = 0.019). Conclusion: Co-existence of other systemic diseases and anti-androgen therapy were the limiting factors for SARS-CoV-2 unvaccination, especially in AGA patients. The importance of SARS-CoV-2 vaccines should be strengthened and popularized in androgen sensitive phenotypes.

Focusing on OB-OC-MΦ Axis and miR-23a to Explore the Pathogenesis and Treatment Strategy of Osteoporosis.

Osteoporosis is a bone metabolic disorder characterized by decreased bone density and deteriorated microstructure, which increases the risk of fractures. The imbalance between bone formation and bone resorption results in the occurrence and progression of osteoporosis. Osteoblast-mediated bone formation, osteoclast-mediated bone resorption and macrophage-regulated inflammatory response play a central role in the process of bone remodeling, which together maintain the balance of the osteoblast-osteoclast-macrophage (OB-OC-MΦ) axis under physiological conditions. Bone formation and bone resorption disorders caused by the imbalance of OB-OC-MΦ axis contribute to osteoporosis. Many microRNAs are involved in the regulation of OB-OC-MΦ axis homeostasis, with microRNA-23a (miR-23a) being particularly crucial. MiR-23a is highly expressed in the pathological process of osteoporosis, which eventually leads to the occurrence and further progression of osteoporosis by inhibiting osteogenesis, promoting bone resorption and inflammatory polarization of macrophages. This review focuses on the role and mechanism of miR-23a in regulating the OB-OC-MΦ axis to provide new clinical strategies for the prevention and treatment of osteoporosis.

Focus on ferroptosis regulation: Exploring novel mechanisms and applications of ferroptosis regulator.

Ferroptosis is a kind of iron-dependent regulatory necrosis characterized by the fatal accumulation of iron-dependent lipid peroxides in the plasma membrane and the final oxidative damage of the cell membrane. Morphologically, ferroptosis features high membrane density, decreased or disappeared cristae, rupture of the mitochondrial outer membrane, plasma membrane integrity loss, cytoplasmic swelling, and organelle swelling. Under physiological conditions, ferroptosis occurs through two major pathways, the extrinsic or transporter-dependent pathway and the intrinsic or enzyme-regulated pathway, triggered by a series of small molecules inside and outside the cell. At present, it is assumed that ferroptosis is mainly related to abnormal toxicity of iron, lipid peroxidation, and mitochondrial dysfunction. With more detailed studies, ferroptosis plays potential pathogenic roles in multisystem diseases as a pathological response, and targeted regulation of ferroptosis in treating ferroptosis-related diseases has broad prospects. In conclusion, it is of great clinical significance to further clarify the specific mechanism of ferroptosis and explore new strategies for ferroptosis regulation. The present review emphatically summarizes the latest mechanism of ferroptosis, focusing on the regulation mechanism and clinical application of ferroptosis inducers and inhibitors. We are devoted to providing new ideas for the further study of ferroptosis and the diagnosis and treatment of ferroptosis-related multisystem diseases.