The engineering application of microbially induced carbonate precipitation(MICP)is limited by pH-dependent conformational dynamics of urease.Focusing on the α-subunit urease from Sporosarcina pasteurii,this study integrated conductivity experiments and constant-pH molecular dynamics simulations to analyze active site conformational dynamics and catalytic function across pH 3-11.Results showed that under neutral conditions(pH 7-8),key histidine residues(HIS139/HIS249)exhibited minimal dis-placement(＜0.5 ?),the longest hydrogen bond lifetime(＞8 ps),highest conformational stability(root mean square deviation,RMSD:0.15-0.18 nm),and optimal catalytic activity(conductivity change rate:0.03 mS/cm·min-1,CaCO3 precipitation:3.84 g).Extreme pH(pH 3/11)induced structural collapse(displacement up to 1.8 ?)and complete activity loss.Simulations revealed that neutral pH sta-bilizes a protonation-dependent cooperative allosteric network by maintaining active site cavity volume(～120 ?3)and moderate conformational coherence(correlation coefficient～0.8).This work deciphers the molecular mechanism of pH-regulated urease dynamics through protonation states,providing theoreti-cal support for MICP applications in acidic mine tailing remediation and alkaline soil stabilization.

Objective:To evaluate the short-term efficacy of endoscopic-laparoscopic regional gastric resection combined with sentinel lymph node basin dissection in patients with early-stage gastric cancer.Methods:This is a retrospective case series study. Data of 17 consecutive early gastric cancer patients from a prospective cohort at Beijing Friendship Hospital,Capital Medical University were analyzed between August 2023 and August 2024. Sixteen cases were from the department of general surgery and 1 from the department of gastroenterology. The cohort included 9 males and 8 females,with a mean age of 61.4 years (range: 46 to 79 years). Clinical data,including demographics,pathological features,surgical procedures,and follow-up outcomes,were collected through medical records and databases. All patients were followed for over 3 months,with follow-up ending on December 5,2024.Results:A total of 17 patients were involved. Among them, 5 patients underwent endoscopic submucosal dissection (ESD) combined with laparoscopic sentinel lymph node dissection (LSBD),and another 3 patients who underwent complete ESD resection received LSBD due to pathological stage meeting the expanded indications. 6 patients who underwent non-curative ESD resection received laparoscopic gastric regional resection (LRG) combined with LSBD,and another 3 patients directly received LRG combined with LSBD. The average number of sentinel lymph nodes dissected before surgery ( M(IQR)) was 8.9 (4.5) (range: 4 to 21),and the detection rate and accuracy rate were both 100%. Postoperative pathology confirmed that there was no metastasis in the sentinel lymph nodes of 5 patients who underwent ESD combined with LSBD and 3 patients who underwent LSBD after complete ESD resection. The vertical and horizontal margins of ESD were all negative. One patient was an absolute indication for ESD. For the 6 patients who underwent non-curative ESD resection combined with LRG and LSBD,the horizontal margins were all negative. Two patients showed 1 metastasis in each of the 21 and 9 sentinel lymph nodes during the operation,and additional distal gastrectomy was performed during the operation. Postoperatively,73 and 39 lymph nodes were retrieved respectively. The former had 1 additional metastasis,while the latter had no metastasis. Among the 3 patients who underwent direct LRG combined with LSBD,the horizontal margins were negative. One patient was confirmed as an absolute indication for ESD by postoperative pathology,and one patient had 1 metastasis in 8 sentinel lymph nodes during the operation,and additional distal gastrectomy was performed. Postoperatively,there was no metastasis in 54 lymph nodes. All patients had no complications such as infection,bleeding,perforation,or death after surgery. Among the 14 patients who did not receive additional radical surgery,they were able to pass gas and defecate within 3 days after surgery,with an average hospital stay of 6 days. The nutritional indicators and gastric radionuclide emptying imaging half-emptying time were similar to those before surgery at 3 months after surgery. Conclusions:Laparoscopic and endoscopic cooperative regional gastrectomy with sentinel lymph node basin dissection has the advantages of minimal invasiveness,preservation of gastric function,and precise treatment. It maybe suitable for patients with early-stage gastric cancer at high risk of lymph node metastasis and has good short-term efficacy.

Objective:To investigate the impact of ubiquitin-specific protease 38 (USP38) on the proliferation and migration of gastric cancer cells.Methods:Between March and September 2023, tissue samples were collected from 18 patients who underwent radical gastrectomy in the Department of General Surgery, Beijing Friendship Hospital Affiliated to Capital Medical University, and had complete clinical data. The samples included tumor tissue, adjacent tumor tissue, and normal tissue. Among the patients, there were 12 males and 6 females, aged between 34 and 71 years, with an average age of 62.5 years. The expression levels of USP38 in different tissue samples were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The functional significance of USP38 was verified through cell experiments and human tissue samples by knocking down or exogenously overexpressing USP38. Potential molecular mechanisms of USP38 were validated through qRT-PCR, MTT, Transwell, Western blot, mass spectrometry, clone formation assays, and immunoprecipitation. Measurement data with a normal distribution are expressed as the mean±standard deviation ( ± s). Comparisons between groups were performed using a t-test or one-way analysis of variance. Measurement data with a skewed distribution were described as [ M( Q1, Q3)], and comparisons between groups were performed using non-parametric tests. Comparisons between counting data were performed using the chi-squared test or Fisher′s exact probability method, with P<0.05 indicating a statistically significant difference. Results:qRT-PCR confirmed that USP38 was highly expressed in gastric cancer tissues compared to normal and paratumor tissues. Furthermore, mass spectrometry analysis identified FASN as a potential downstream target of USP38, and immunoprecipitation experiments demonstrated a positive correlation between its expression level and USP38. USP38 was highly expressed in the SGC7901, AGS, and HGC27 gastric cancer cell lines. Knockdown of USP38 reduced FASN expression, thereby inhibiting cell proliferation and migration abilities. While the ability of cell proliferation and migration was increased significantly.Conclusions:USP38 is highly expressed in gastric cancer cells and promotes their proliferation and migration, potentially through downstream FASN-mediated fatty acid synthesis.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective:To investigate the clinical management,complications,and prognostic prediction model of bronchopulmonary dysplasia(BPD)in preterm infants.Methods:A total of 854 very preterm infants(gestational age ≤ 32 weeks)admitted to the Neonatal Intensive Care Unit(NICU)of Shanghai Children's Hospital from January 2018 to December 2022 were retrospectively enrolled.After applying inclusion and exclusion criteria,713 infants were included.Based on the 2018 National Institute of Child Health and Human Development(NICHD)diagnostic criteria for BPD,the cohort was divided into a BPD group(n=164)and a non-BPD group(n=549).Clinical data of infants and maternal characteristics were compared between groups.Univariate and stepwise multivariate logistic regression analyses were performed to identify independent risk factors for BPD and evaluate clinical management.A nomogram model was subsequently developed to predict BPD prognosis.Results:Gestational age,duration of non-invasive ventilation,total oxygen therapy time,total hospital stay,hemodynamically significant patent ductus arteriosus(hsPDA),maximum diameter of patent ductus arteriosus(PDA),fetal growth restriction(FGR),use of vasoactive agents,and proportion of pulmonary surfactant administration were identified as independent risk factors for BPD(all P＜0.05,OR＞0).The nomogram model demonstrated excellent predictive performance,with an area under the receiver operating characteristic curve(AUC)of 0.93 and a calibration curve slope approaching 1.The Hosmer-Lemeshow goodness-of-fit test indicated satisfactory model calibration(x2=8.2865,P=0.406).Conclusion:Gestational age,non-invasive ventilation duration,total oxygen therapy time,total hospital stay,hsPDA,PDA maximum diameter,FGR,vasoactive agents,and pulmonary surfactant use are critical predictors of BPD in preterm infants.The prognostic models for BPD incidence and severity,constructed based on these factors,exhibit strong predictive accuracy and may serve as a valuable clinical tool for risk stratification and early intervention.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

Objective:To investigate the clinical management,complications,and prognostic prediction model of bronchopulmonary dysplasia(BPD)in preterm infants.Methods:A total of 854 very preterm infants(gestational age ≤ 32 weeks)admitted to the Neonatal Intensive Care Unit(NICU)of Shanghai Children's Hospital from January 2018 to December 2022 were retrospectively enrolled.After applying inclusion and exclusion criteria,713 infants were included.Based on the 2018 National Institute of Child Health and Human Development(NICHD)diagnostic criteria for BPD,the cohort was divided into a BPD group(n=164)and a non-BPD group(n=549).Clinical data of infants and maternal characteristics were compared between groups.Univariate and stepwise multivariate logistic regression analyses were performed to identify independent risk factors for BPD and evaluate clinical management.A nomogram model was subsequently developed to predict BPD prognosis.Results:Gestational age,duration of non-invasive ventilation,total oxygen therapy time,total hospital stay,hemodynamically significant patent ductus arteriosus(hsPDA),maximum diameter of patent ductus arteriosus(PDA),fetal growth restriction(FGR),use of vasoactive agents,and proportion of pulmonary surfactant administration were identified as independent risk factors for BPD(all P＜0.05,OR＞0).The nomogram model demonstrated excellent predictive performance,with an area under the receiver operating characteristic curve(AUC)of 0.93 and a calibration curve slope approaching 1.The Hosmer-Lemeshow goodness-of-fit test indicated satisfactory model calibration(x2=8.2865,P=0.406).Conclusion:Gestational age,non-invasive ventilation duration,total oxygen therapy time,total hospital stay,hsPDA,PDA maximum diameter,FGR,vasoactive agents,and pulmonary surfactant use are critical predictors of BPD in preterm infants.The prognostic models for BPD incidence and severity,constructed based on these factors,exhibit strong predictive accuracy and may serve as a valuable clinical tool for risk stratification and early intervention.

An assay was established for detection of toxigenic Clostridioides difficile by combining microfluidic chip analysis with immunochromatography,and its performance was evaluated and compared with those of the Xpert C.difficile/Epi and VIDAS CD AB tests.Primer pairs were designed according to the tcdB and tpi genes in C.difficile.The specificity,limit of detection,reproducibility,and stability were evaluated.A total of 215 stool samples from patients with diarrhea were collected and tested in parallel with the Xpert C.difficile/Epi,VIDAS CDAB,and our assay.C.difficile was isolated from samples,and the tcdB gene was identified when discrepant results were obtained from the three above assays.Our assay showed no cross-reaction with other diarrhea-associated pathogens.Its reproducibility was 100％in testing of two standard plasmids containing tcdB and tpi genes at two concentrations(105 and 102 copies/μL).Two standard plasmids were detected after the PCR and immunochromatography reagents had been stored for 3,6,9,and 12 months,and all the results were posi-tive.The limit of detection was 10 copies/μL for toxigenic C.difficile.Testing of 33 samples positive for C.difficile with our assay(33/215,15.3％)yielded findings statistically coherent with those of the Xpert C.difficile/Epi test(kappa value=0.965).The sensitivity,specificity,positive predictive value,and negative predictive value of our assay,with respect to Xpert C.difficile/Epi as the standard,were 94.3％,100.0％,100.0％,and 98.9％;these values were significantly higher than those of VIDAS CDAB(60.0％,98.9％,91.3％,and 92.7％)(Kappa=0.714,OR=157.50,95％CI:62.03-847.28,P=0.013).In conclusion,our newly developed assay is specific,stable,and reproducible,and may be used for rapid and accu-rate detection of toxigenic C.difficile.The assay could be used for C.difficile infection screening in outpatient and emergen-cy,community medical service center,and epidemiological settings.