Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Objective To translate the Context Assessment for Community Health(COACH)scale into Chinese,thereby providing a standardized measurement tool for context assessment in clinical evidence-based practice.Methods The scale was translated following the Brislin translation model,ultimately forming the Chinese version of the COACH scale.Using convenience sampling,584 healthcare professionals were recruited from 3 tertiary hospitals in Jiangxi,Henan,and Liaoning provinces and 2 community hospitals in Liaoning province from May to September 2024 to evaluate the reliability and validity of the scale.In October 2024,the Chinese version of COACH was applied to 44 healthcare professionals in a hypertension specialist ward of a provincial tertiary hospital.Results Of the 584 distributed questionnaires,519 valid questionnaires were collected(the effective response rate of 88.87％).The Chinese version consists of 7 dimensions with 42 items.The overall Cronbach's α coefficient was 0.975;the McDonald's omega coefficient was 0.979;split-half reliability was 0.808,and the test-retest reliability was 0.917.The scale-content validity index/average was 0.950,and the scale-content validity index/universal agreement was 0.980,with item-content validity index ranging from 0.775 to 1.000.Exploratory factor analysis extracted 7 factors,accounting for 79.260％of the cumulative variance,with factor loadings ranging from 0.569 to 0.954.Confirmatory factor analysis showed good model fit.The preliminary application results showed that the total score of the scale was 185.18±17.82.The correlation coefficients between dimensions and total score ranged from 0.116 to 0.905.Conclusion The Chinese version of the COACH scale demonstrates good reliability and validity,making it suitable as a context measurement tool for implementation research at different stages in clinical and public health settings.

Objective To systematically assess the efficacy and safety of combining acupoint massage with lactulose for constipation treatment.Methods Randomized controlled trials on the effects of acupressure combined with lactulose on constipation were searched in PubMed,Web of Science,Cochrane Library,Embase,China National Knowledge Infrastructure,SinoMed,VIP and Wanfang Data Knowledge Service Platform.The search timeframe was from the establishment of the database to July 2024,and Meta-analysis was performed using RevMan5.3 and Stata15.1 software.Results A total of 8 randomized controlled trials including 675 study participants were included.Meta-analysis showed that the acupoint massage combined with lactulose group was superior to control group in terms of total effective rate,abdominal distension score,and constipation quality of life score.Furthermore,its recurrence rate was lower than that of control group.Both groups showed no statistically significant difference in adverse reactions(P＞0.05).Conclusion Acupressure combined with lactulose can effectively improve the efficiency and quality of life in the treatment of constipation,and can be safe.Due to the limitation of the quantity and quality of the included literature,more high-quality studies with long-term follow-up are still needed to supplement and validate the above conclusions in the future.

Objective:This study aims to explore the characteristics of body temperature(BT)of the elderly population in China and the relationship with health status.Methods:This is a cross-sectional study.The data were derived from the China Health and Nutrition Study(CHNS)in 2015.A total of 4 176 elderly people over 60 years old were enrolled for analysis(1968 males, and 2208 females). The participants were divided into three groups according to their BT values: hypothermia group(BT<36.5℃), moderate BT group(36.5℃≤BT<37.0℃), and hyperthermia group(37.0℃≤BT<37.5℃). The differences in health status among each group were compared based on the disease conditions(four-week prevalence rate)in the past four weeks.Multivariate logistic regression analysis was performed to explore the relationships between BT and the four-week prevalence rate.Results:Among the elderly population included in the analysis, the average age was 68.4 ± 6.9 years(ranging from 60 to 99 years). The average BT of the elderly was 36.40 ± 0.37℃(males: 36.42 ± 0.37℃; females: 36.38 ± 0.37℃).3 348 study subjects were aged between 60-74 years old, while 828 study subjects were aged between75-99 years old.The older the age, the lower the body temperature.Of the participants, 2 212(53.0%)elderly people belonged to the hypothermia group, 1 656(39.6%)belonged to the moderate BT group, and 308(7.4%)belonged to the hyperthemia group.Among 4 176 elderly people, a total of 1368 had suffered from disease in the past four weeks(31.3%)The four-week prevalence rates of each group were as follows: the hypothermia group(33.1%), the moderate BT group(29.8%); hyperthemia group(26.6%)( χ2=8.403, P=0.015). Multivariable logistic regression analysis indicated that for every 1℃ increases in BT among the elderly, the four-week prevalence rate decreased by 22%( OR=0.78, 95% CI=0.65-0.94, P=0.01). Conclusions:The BT of the elderly is generally lower than the current standard, and the lower the BT, the higher the four-week prevalence rate.Raising the BT of the elderly may help them improve their physical condition.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective:To evaluate the effectiveness and safety of zoledronic acid in patients with Paget′s disease of bone based on clinical data from a single medical center.Methods:This retrospective study included 24 patients diagnosed with Paget′s disease of bone and treated with zoledronic acid at Peking Union Medical College Hospital between January 2009 and June 2020. Demographic data, clinical symptoms, treatment efficacy, and safety outcomes were collected. The primary efficacy measure was serum alkaline phosphatase(ALP) levels. Treatment was considered effective if ALP levels returned to normal or decreased by more than 75% from baseline in the difference between the ALP level and its normal median value.Results:Among the 24 patients with Paget′s bone disease, the most commonly affected site was the skull(in 17 cases). All patients received a single 5 mg intravenous infusion of zoledronic acid. Serum ALP levels significantly decreased after treatment. Among the 15 patients who completed at least 3 months of follow-up, all achieved treatment success. The median time for serum ALP levels to reach the target was 13.1(9.4, 26.1) weeks. In 12 patients, ALP levels normalized within a medium of 16.9(11.5, 37.3) weeks, and remained stable over a medium follow-up of 4.56(2.42, 5.71) years. The most common side effects were hypocalcemia(21 cases, 87.5%) and flu-like symptoms(17 cases, 70.8%). Seven patients had severe hypocalcemia(serum calcium<1.75 mmol/L), and they had higher baseline levels of ALP, calcium, and phosphorus compared to those with mild hypocalcemia.Conclusions:Zoledronic acid 5 mg intravenous infusion effectively controlled disease activity in patients with Paget′s disease of bone. Generally, Most patients achieved treatment goals within 3-4 months, with sustained remission for a median of 4 years. Hypocalcemia was the most frequent side effect, underscoring the importance of timely calcium and vitamin D supplementation.