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.

OBJECTIVE To study the improvement effect and mechanism of Shengmai powder on heart failure （HF） mice with qi-yin deficiency. METHODS The mice were randomly divided into blank group （water）， model group （water）， Shengmai powder low-， medium-， and high-dose groups [2.61， 5.22 and 10.44 g/kg （based on crude drug dosage）] and positive control group （metoprolol， 30 mg/kg）， with 10 mice in each group. Except for the blank group， all other groups were subcutaneously injected with D-galactose， and a qi-yin deficiency HF mice model was established by continuous food restriction and weight-bearing swimming. At the same time of modeling， the corresponding medicine/water was gavaged once a day for five weeks. The general state of mice was recorded and the traditional Chinese medicine （TCM） syndrome score was evaluated. Behavioral experiments were conducted to investigate the total distance of open field action， the percentage of immobility time， and the swimming exhaustion time of mice. The contents of aspartate transaminase （AST）， creatine kinase （CK） and lactate dehydrogenase （LDH） in the serum of mice were detected； cardiac function indexes [heart rate， left ventricular ejection fraction （LVEF）， left ventricular end systolic diameter （LVESD）， left ventricular end diastolic diameter （LVEDD）， left ventricular mass index and whole heart mass index] were all detected； the histopathological morphology of mice myocardium was observed； the level of cardiomyocyte apoptosis in mice was detected； mRNA expression levels of B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and Cleaved-caspase-3 in myocardial tissue of mice were detected； the phosphorylation levels of sarcoplasmic reticulum calcium regulatory related proteins [ryanodine receptor 2 （RyR2） and phospholamban （PLB）] in myocardial tissue of mice were detected. RESULTS Compared with the blank group， the body weight， total distance of open field action， swimming exhaustion time， LVEF， LVEDD， Bcl-2 mRNA expression level in myocardial tissue and PLB protein phosphorylation level in the model group were significantly reduced/shortened （P＜0.05）； TCM syndrome score， the percentage of immobility time， heart rate， LVESD， left ventricular mass index， whole heart mass index， cardiomyocyte apoptosis rate， the contents of CK， LDH and AST in serum， mRNA expression levels of Cleaved-caspase-3 and Bax and the phosphorylation level of RyR2 protein in myocardial tissue were significantly increased （P＜0.05）； there were inflammatory cell infiltration， disordered cell arrangement and obvious myocardial interstitial fibrosis in myocardial tissue. After the intervention of Shengmai powder， most of the above quantitative indexes in mice were significantly reversed （P＜0.05）， the inflammatory cell infiltration in myocardial tissue was reduced， and the degree of fibrosis was significantly reduced. CONCLUSIONS Shengmai powder can improve cardiac function， reduce the level of cardiomyocyte apoptosis and myocardial fibrosis in HF mice with qi-yin deficiency. Its mechanism may be related to the regulation of the expression of sarcoplasmic reticulum calcium regulation related proteins.

Progressive pulmonary fibrosis (PPF) is a progressive and lethal condition with few effective treatment options. Improvements in quality of life for patients with PPF remain limited even while receiving treatment with approved antifibrotic drugs. Traditional Chinese medicine (TCM) has the potential to improve cough, dyspnea and fatigue symptoms of patients with PPF. TCM treatments are typically diverse and individualized, requiring urgent development of efficient and precise design strategies to identify effective treatment options. We designed an innovative Bayesian adaptive two-stage trial, hoping to provide new ideas for the rapid evaluation of the effectiveness of TCM in PPF. An open-label, two-stage, adaptive Bayesian randomized controlled trial will be conducted in China. Based on Bayesian methods, the trial will employ response-adaptive randomization to allocate patients to study groups based on data collected over the course of the trial. The adaptive Bayesian trial design will employ a Bayesian hierarchical model with "stopping" and "continuation" criteria once a predetermined posterior probability of superiority or futility and a decision threshold are reached. The trial can be implemented more efficiently by sharing the master protocol and organizational management mechanisms of the sub-trial we have implemented. The primary patient-reported outcome is a change in the Leicester Cough Questionnaire score, reflecting an improvement in cough-specific quality of life. The adaptive Bayesian trial design may be a promising method to facilitate the rapid clinical evaluation of TCM effectiveness for PPF, and will provide an example for how to evaluate TCM effectiveness in rare and refractory diseases. However, due to the complexity of the trial implementation, sufficient simulation analysis by professional statistical analysts is required to construct a Bayesian response-adaptive randomization procedure for timely response. Moreover, detailed standard operating procedures need to be developed to ensure the feasibility of the trial implementation. Please cite this article as: Zhang C, Nie YS, Zhang CT, Yang HJ, Zhang HR, Xiao W, Cui GF, Li J, Li SJ, Huang QS, Yan SY. An adaptive Bayesian randomized controlled trial of traditional Chinese medicine in progressive pulmonary fibrosis: Rationale and study design. J Integr Med. 2025; 23(2): 138-145.
Female ; Humans ; Male ; Bayes Theorem ; Disease Progression ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Pulmonary Fibrosis/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; Adaptive Clinical Trials as Topic

OBJECTIVES: This study aimed to analyze the influence of drug factors on the efficacy of bisphosphonate for chronic nonbacterial osteomyelitis to provide a reference for clinical treatment and promote clinical rational drug use by evaluation of effectiveness and safety of bisphosphonate treatment of chronic nonbacterial osteomyelitis. METHODS: Literature on the treatment of chronic nonbacterial osteomyelitis by using bisphosphonate was collected and analyzed from PubMed, Medline, Embase, Cochrane, ISI Web of Knowledge, CNKI, VIP, and Wanfang databases. RESULTS: A total of 489 cases were collected, with an average complete response rate of clinical presentation, laboratory tests and imaging findings of 80.37%, 80.56% and 79.22%, respectively. Except for opadronate, risedronate, ibandronate, pamidronate, alendronate, neidronate and zoledronate showed good efficacy, and the average complete response rates were 100%, 100%, 81.64%, 87.50%, 69.23% and 69.23%, respectively.The study found that in the pamidronate group, the average complete response rate of 0.5-1 mg/kg (maximum single dose≤60 mg) subgroup and the frequency of administration once every 3 months subgroup were better than other subgroups. CONCLUSIONS Bisphosphonate could be used to treat chronic nonbacterial osteomyelitis, which of efficacy were affected by different drug types, dose and frequency of administration. The optimal dose and frequency of administration of pamidronate were 0.5-1 mg/kg (maximum single dose≤60 mg) and once every 3 months, respectively.
Osteomyelitis/drug therapy* ; Humans ; Diphosphonates/administration & dosage* ; Chronic Disease ; Bone Density Conservation Agents/administration & dosage* ; Female ; Pamidronate ; Middle Aged ; Male

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

A molecularly imprinted electrochemical sensor for rapid detection of tenuazonic acid(TeA)was developed based on the Au-MoS2/MOF(Fe2+/Fe3+)high-efficiency catalytic cycle amplification strategy,using p-aminobenzoic acid(PABA)as the functional monomer,and TeA as the template molecule.The molecularly imprinted polymer(MIP)was prepared on the surface of Au-MoS2/MOF(Fe2+/Fe3+)modified electrode through electropolymerization.By introducing flower-like MoS2 nanoflakes(MoS2 NFs)as a co-catalyst into a mixed-valence structured Fe-MOF(Fe2+/Fe3+),the H2O2 electrochemical signal of the MIP/Au-MoS2/MOF(Fe2+/Fe3+)/GCE was significantly enhanced.Under optimal conditions,the sensor exhibited good selectivity and high sensitivity toward TeA.A linear relationship(R2=0.992)was observed between the electrochemical response and TeA concentration in the range of 0.001-10 μg/kg,with a detection limit of 0.3 ng/kg.The developed method was successfully applied to determination of TeA in fruit samples,with recoveries ranging from 90.8%to 110.8%,and relative standard deviations from 1.9%to 8.4%.

Objective To perform a regression analysis on the predictive value of serum micro-RNAs(miR)for early neurological deterioration(END)in patients with branch atheromatous dis-ease(BAD).Methods A total of 134 BAD patients admitted in our department from February 2020 to February 2023 were enrolled,and according to the END status,they were divided into de-terioration group(28 cases)and non-deterioration group(106 cases).Serum levels of miR-130a,miR-210,miR-141-3p and miR-29a-3p were measured at admission.NIHSS score was used to eval-uate the END status at admission and at 7 d after admission.Binary logistic regression analysis was adopted to construct a model of above four miRs in predicting END in BAD patients.ROC curve was plotted to assess the predictive value of the four miRs alone or combined together for END.Results The serum levels of miR-130a and miR-210 were significantly higher,while those of miR-141-3p and miR-29a-3p were obviously lower in the deterioration group than the non-deterioration group(P＜0.01).Logistic regression analysis indicated that serum miR-130a,miR-210,miR-141-3p and miR-29a-3p were independent predictors of END in BAD patients(P＜0.05,P＜0.01).ROC curve analysis showed that the AUC value of the four miRs combined together in predicting END in BAD patients was 0.977(95％CI:0.936-0.995),with a sensitivity of 96.43％and a specificity of 90.57％,and the combined detection exhibited better predictive effi-ciency than each indicator alone(P＜0.01).Conclusion Serum miR-130a,miR-210,miR-141-3p and miR-29a-3p have certain value in predicting END in BAD patients,and their combined detec-tion can enhance its predictive efficiency.

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.