Background: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Objective To addresses the challenges arising from the rapid expansion of pharmaceutical clinical trials and the growing demands for quality management,this paper investigates the application of low-code technology in project management.Its goals are to enhance the operational efficiency and execution capabilities of clinical trial institutions,ensure trial quality and safety,and accelerate the translation of pharmaceutical scientific achievements.Methods A brainstorming session was conducted to analyze the technical and functional requirements for managing pharmaceutical clinical trial projects.Utilizing the ＂template design＂ and ＂decision analysis＂ functionalities of low-code technology,the study adopted a modular and visually driven data management approach to develop a system compliant with Good Clinical Practice(GCP)standards.This system integrates key functionalities,including project progress management,funding management,drug inventory management,and quality control.Its effectiveness was evaluated through real-world operation and performance validation.Results The system had demonstrated stable operation with substantial improvements in practical application.Compared with conventional management approaches,it significantly enhanced project management efficiency:the time required for project schedule management was reduced by 80%,the efficiency of financial processing increased by 95%,drug inventory management efficiency improved by 75%,and the time spent on quality control was shortened by 60%.Conclusion The pharmaceutical clinical trial project management system developed using low-code technology offers substantial advantages and promising application potential.It represents a critical practice in applying digital and intelligent tools to advance pharmaceutical productivity in the medical and healthcare sectors.

Objective:To develop a vasectomy intention scale (VIS) and evaluate its reliability and validity for assessing men's intentions toward vasectomy.Methods:Based on the Theory of Planned Behavior, the VIS was developed through a process that included literature review, panel discussions, expert consultations, and a pilot survey. A total of 264 men seeking vasectomy consultation at the Andrology Center, Department of Urology, the Third Xiangya Hospital of Central South University between December 2023 and December 2024 were recruited to assess reliability and validity of the VIS.Results:The VIS comprises 11 items across three dimensions: "background" factors, "stance and behavior" factors and "information" factors. The scale demonstrated satisfactory internal consistency (Cronbach's α=0.739). Correlations between each dimension and the total scale ("background" factors r=0.849, "stance and behavior" factors r=0.744, "information" factors r=0.440) exceeded inter-dimension correlations (ranging from 0.145 to 0.312), confirming robust construct validity. The vasectomy rates among men with different intention levels were 65.7% (92/140) in the high-intention group, 28.9% (33/114) in the moderate-intention group, and 0% (0/11) in the low-intention group, with a statistically significant difference (χ2=43.42, P<0.001). Conclusion:The VIS exhibits strong reliability and validity, serving as a validated instrument for measuring the strength of men's vasectomy intentions.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective:To compare the efficacy of O-arm navigation-assisted and conventional posterior cervical expansive open-door laminoplasty (CEOL) via the intermuscular approach in the treatment of cervical spinal cord injury without fracture-dislocation (CSCIWFD).Methods:A prospective cohort study was conducted to analyze the clinical data of 60 CSCIWFD patients who were admitted to Zhengzhou Orthopedic Hospital from May 2021 to May 2023, with compression at C3-C6. Patients were randomly divided into two groups: 30 patients underwent O-arm navigation-assisted intermuscular approach CEOL (navigation-assisted group) and 30 patients underwent conventional intermuscular approach CEOL (conventional surgery group). Surgical duration, intraoperative blood loss, postoperative drainage volume, and total surgical blood loss were compared between the two groups. At 2 weeks postoperatively, CT scan was performed to evaluate the accuracy of hinge or open-door position preparation of the surgical segments. Visual analogue scale (VAS) for neck and shoulder pain and Japanese Orthopedic Association (JOA) scores were compared between the two groups preoperatively, at 2 weeks, 6 months postoperatively, and at the last follow-up. Complication rates were also evaluated.Results:A total of 60 patients with CSCIWFD were included, comprising 35 males and 25 females, aged 35-77 years [(50.9±8.6)years]. All the patients were followed up for 12-24 months [(16.9±3.1)months]. The surgical duration and intraoperative blood loss were (121.6±17.9)minutes and (144.7±44.2)ml in the navigation-assisted group, shorter or less than (132.3±14.6)minutes and (178.7±48.7)ml in the conventional surgery group ( P<0.05). There were no statistically significant differences in postoperative drainage volume and total surgical blood loss between the two groups ( P>0.05). CT scan reviewed at 2 weeks postoperatively revealed that the accuracy rate of hinge and open-door position preparation of the surgical segments in the navigation-assisted group was 99.2% (119/120), significantly higher than 86.7% (104/120) in the conventional surgery group ( P<0.01). Before operation and at 2 weeks, 6 months postoperatively, and at the last follow-up, the VAS scores for neck and shoulder pain and JOA scores in the navigation-assisted group were 5.0(4.0, 7.0)points and (8.7±2.8)points, 3.0(2.0, 4.0)points and (10.2±2.5)points, 2.0(1.0, 2.0)points and (1 3.0±1.8)points, and 1.0(1.0, 2.0)points and (13.9±1.5)points respectively, while in the conventional surgery group, the VAS scores and JOA scores were 5.5(5.0, 6.3)points and (8.8±2.6)points, 4.0(3.0, 4.0)points and (10.4±2.5)points, 2.0(1.0, 3.0)points and (12.9±2.2)points, and 2.0(1.0, 2.0)points and (13.8±2.0)points ( P>0.05). Both groups showed improvement in neck and shoulder VAS scores and JOA scores at 2 weeks, 6 months postoperatively, and at the last follow-up, compared to preoperative scores ( P<0.05); further improvement was observed at 6 months postoperatively and at the last follow-up compared to that at 2 weeks postoperatively ( P<0.05). There were no significant differences between neck and shoulder VAS scores or JOA scores at 6 months postoperatively and at the last follow-up ( P>0.05). In the navigation-assisted group, 2 patients had axial neck-shoulder pain postoperatively, with a complication rate of 7% (2/30); while in the conventional surgery group, 7 patients had axial neck-shoulder pain and one patient developed cerebrospinal fluid leakage and low-pressure headache, with a complication rate of 27% (8/30) ( P<0.05). Conclusion:Compared to the conventional intermuscular approach, O-arm navigation-assisted intermuscular approach CEOL for CSCIWFD reduces surgical duration and intraoperative blood loss, improves the accuracy of hinge and open-door position preparation, and lowers complication rates.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective:To evaluate the role of NOD-like receptor protein 3 (NLRP3) inflammasome-mediated microglia activation in myocardial ischaemia-reperfusion-induced brain injury in mice.Methods:Fifty-two SPF healthy male wild-type C57BL/6 mice and 52 NLRP3 -/- mice, aged 8-10 weeks, were divided into 4 groups ( n=26 each) using a random number table method: wild type sham operation group (W-S group), wild type myocardial ischemia-reperfusion group (W-IR group), NLRP3 -/- sham operation group (NLRP3 -/--S group), and NLRP3 -/- myocardial ischemia-reperfusion group (NLRP3 -/--IR group). The myocardial ischemia-reperfusion-induced brain injury model was established by ligating the left anterior descending coronary artery for 45 min followed by 24 h of reperfusion in anesthetized mice. The cognitive function was evaluated using the modified Morris water maze test at 24 h of reperfusion. The mice were sacrificed after blood specimens were collected, and brain tissues were obtained for measurement of the blood-brain barrier permeability and water content, for microscopic examination of the pathological changes of brain tissues, and for determination of serum S-100β protein and neuron-specific enolase (NSE) concentrations, contents of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α) in hippocampal tissues (by enzyme-linked immunosorbent assay), expression of NLRP3, apoptosis-associated speck-like protein (ASC), cleaved cysteine aspartate protease 1 (cleaved-caspase-1), gasdermin D (GSDMD), ionized calcium-binding adapter molecule 1 (Iba-1), and occludin in hippocampal tissues (by immunofluorescence and/or Western blot). The apoptosis rate of neurons and density of dendritic spine were calculated. Results:Compared with sham operation group, the escape latency was significantly prolonged, the number of crossing the original platform was decreased, and the time spent in the target quadrant was shortened, the concentrations of serum S-100β protein and NSE were increased, the blood-brain barrier permeability and brain water content were increased, the dendritic spine density in the hippocampal CA1 area was decreased, the contents of IL-1β, IL-6 and TNF-α were increased, the expression of NLRP3, ASC, cleaved-caspase-1, GSDMD and Iba-1 was up-regulated, and the expression of occludin was down-regulated ( P<0.05), and the pathological injury to brain tissues was found in ischemia-reperfusion group. Compared with W-IR group, the escape latency was significantly shortened, the number of crossing the original platform was increased, and the time spent in the target quadrant was prolonged, the concentrations of serum S-100β protein and NSE were decreased, the blood-brain barrier permeability and brain water content were decreased, the dendritic spine density in the hippocampal CA1 area was increased, the contents of IL-1β, IL-6 and TNF-α were decreased, the expression of NLRP3, ASC, cleaved-caspase-1, GSDMD and Iba-1 was down-regulated, and the expression of occludin was up-regulated ( P<0.05), and the pathological injury to brain tissues was alleviated in NLRP3 -/--IR group. Conclusions:NLRP3 inflammasome-mediated microglia activation is involved in myocardial ischaemia-reperfusion-induced brain injury in mice.

Objective:To evaluate whether the mechanism by which high glucose attenuated the cardioprotective effect of sevoflurane postconditioning was associated with the hypoxia-inducible factor-1α (HIF-1α)/monocarboxylate transporter 4 (MCT4) signaling pathway in rat cardiomyocytes.Methods:H9C2 cardiomyocytes were cultured at a 1∶4 ratio and then divided into 8 groups ( n=21 each) using a table of random numbers: control group (N+ Con group), hypoxia-reoxygenation (H/R) group (N+ H/R group), sevoflurane postconditioning group (N+ SPostC group), high glucose control group (H+ Con group), high glucose-H/R group (H+ H/R group), high glucose sevoflurane postconditioning group (H+ SPostC group), high glucose sevoflurane postconditioning + HIF-1α agonist group (H+ SPostC+ D group), and high glucose sevoflurane postconditioning + HIF-1α agonist + MCT4 inhibitor group (H+ SPostC+ D+ A group). N+ Con, N+ H/R and N+ SPostC groups were cultured in conventional culture dishes, while high-glucose group was incubated in high-glucose (35 mmol/L) DMEM. Cells were subjected to 3 h of hypoxia in serum-free and glucose-free DMEM using a three-gas incubator, followed by 3 h of reoxygenation in fresh DMEM in a CO 2 incubator. Sevoflurane postconditioning was performed as follows: Cells were incubated at 37 ℃ in a three-gas incubator filled with sevoflurane (2.4%) for 15 min. At 2 h before hypoxia, H+ SPostC+ D group was incubated in medium containing 1 mmol/L DMOG (HIF-1α agonist), and H+ SPostC+ D+ A group was incubated in medium containing 1 mmol/L DMOG and 10 μmol/L AZD0095 (MCT4 inhibitor). The viability of cardiomyocytes (by CCK8 assay), levels of LDH in culture medium (by microplate assay), levels of lactate (by WST-8 assay), levels of ATP (by chemiluminescence assay), apoptosis rate of cells (by flow cytometry), mitochondrial membrane potential (by fluorescence probe assay), and expression of HIF-1α and MCT4 (by Western blot) were measured. Results:Compared with N+ H/R group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly increased, the levels of LDH in culture medium and apoptosis rate of cells were decreased, and the expression of HIF-1α and MCT4 was up-regulated in N+ SPostC group ( P<0.05). There were no significant differences in each parameter between H+ H/R group and H+ SPostC group ( P>0.05). Compared with H+ SPostC group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly increased, the levels of LDH in culture medium and apoptosis rate of cells were decreased, and the expression of HIF-1α and MCT4 was up-regulated in H+ SPostC+ D group ( P<0.05). Compared with H+ SPostC+ D group, the cell viability, levels of lactate, levels of ATP and mitochondrial membrane potential were significantly decreased, the levels of LDH in culture medium and apoptosis rates of cells were increased, and the expression of HIF-1α and MCT4 was down-regulated in H+ SPostC+ D+ A group ( P<0.05). Conclusions:The mechanism by which high glucose attenuates the cardioprotective effect of sevoflurane postconditioning may be related to the inhibition of the HIF-1α/MCT4 signaling pathway in rat cardiomyocytes.

Objective:To compare the efficacy of O-arm navigation-assisted and conventional posterior cervical expansive open-door laminoplasty (CEOL) via the intermuscular approach in the treatment of cervical spinal cord injury without fracture-dislocation (CSCIWFD).Methods:A prospective cohort study was conducted to analyze the clinical data of 60 CSCIWFD patients who were admitted to Zhengzhou Orthopedic Hospital from May 2021 to May 2023, with compression at C3-C6. Patients were randomly divided into two groups: 30 patients underwent O-arm navigation-assisted intermuscular approach CEOL (navigation-assisted group) and 30 patients underwent conventional intermuscular approach CEOL (conventional surgery group). Surgical duration, intraoperative blood loss, postoperative drainage volume, and total surgical blood loss were compared between the two groups. At 2 weeks postoperatively, CT scan was performed to evaluate the accuracy of hinge or open-door position preparation of the surgical segments. Visual analogue scale (VAS) for neck and shoulder pain and Japanese Orthopedic Association (JOA) scores were compared between the two groups preoperatively, at 2 weeks, 6 months postoperatively, and at the last follow-up. Complication rates were also evaluated.Results:A total of 60 patients with CSCIWFD were included, comprising 35 males and 25 females, aged 35-77 years [(50.9±8.6)years]. All the patients were followed up for 12-24 months [(16.9±3.1)months]. The surgical duration and intraoperative blood loss were (121.6±17.9)minutes and (144.7±44.2)ml in the navigation-assisted group, shorter or less than (132.3±14.6)minutes and (178.7±48.7)ml in the conventional surgery group ( P<0.05). There were no statistically significant differences in postoperative drainage volume and total surgical blood loss between the two groups ( P>0.05). CT scan reviewed at 2 weeks postoperatively revealed that the accuracy rate of hinge and open-door position preparation of the surgical segments in the navigation-assisted group was 99.2% (119/120), significantly higher than 86.7% (104/120) in the conventional surgery group ( P<0.01). Before operation and at 2 weeks, 6 months postoperatively, and at the last follow-up, the VAS scores for neck and shoulder pain and JOA scores in the navigation-assisted group were 5.0(4.0, 7.0)points and (8.7±2.8)points, 3.0(2.0, 4.0)points and (10.2±2.5)points, 2.0(1.0, 2.0)points and (1 3.0±1.8)points, and 1.0(1.0, 2.0)points and (13.9±1.5)points respectively, while in the conventional surgery group, the VAS scores and JOA scores were 5.5(5.0, 6.3)points and (8.8±2.6)points, 4.0(3.0, 4.0)points and (10.4±2.5)points, 2.0(1.0, 3.0)points and (12.9±2.2)points, and 2.0(1.0, 2.0)points and (13.8±2.0)points ( P>0.05). Both groups showed improvement in neck and shoulder VAS scores and JOA scores at 2 weeks, 6 months postoperatively, and at the last follow-up, compared to preoperative scores ( P<0.05); further improvement was observed at 6 months postoperatively and at the last follow-up compared to that at 2 weeks postoperatively ( P<0.05). There were no significant differences between neck and shoulder VAS scores or JOA scores at 6 months postoperatively and at the last follow-up ( P>0.05). In the navigation-assisted group, 2 patients had axial neck-shoulder pain postoperatively, with a complication rate of 7% (2/30); while in the conventional surgery group, 7 patients had axial neck-shoulder pain and one patient developed cerebrospinal fluid leakage and low-pressure headache, with a complication rate of 27% (8/30) ( P<0.05). Conclusion:Compared to the conventional intermuscular approach, O-arm navigation-assisted intermuscular approach CEOL for CSCIWFD reduces surgical duration and intraoperative blood loss, improves the accuracy of hinge and open-door position preparation, and lowers complication rates.

AIM To study the chemical constituents from Tetrastigma hemsleyanum Diels et Gilg and their antitumor activity in vitro.METHODS Silica gel,ODS,Sephadex LH-20 and semi-preparative HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antitumor activity in vitro was determined by MTT mothod.RESULTS Twenty-eight compounds were isolated and identified as triphyllin A(1),eruberin B(2),(2S,4R)-5,7-dihydroxy-4,4'-dimethyl-6,8-dimethyl-flavan-5-O-β-D-6-acetylglucopyranoside-7-O-β-D-glucopyranoside(3),eruberin A(4),abacopterin Ⅰ(5),matteucinol(6),homoerodictyol(7),(2S)-5,3',4'-trihydroxy-7-methoxy-flavanone(8),(2S)-5,2',5'-trihydroxy-7-methoxyflavanone(9),galinsonside B(10),quercetin-3-O-β-D-glucopyranoside(11),kaempferol 3-O-robinobioside(12),rutin(13),geniposide(14),jasminoside A(15),β-sitostenone(16),sitosterol palmitate(17),β-sitosterol(18),ursolic acid(19),hyptadienic acid(20),3,4-dihydroxybenzoic acid(21),3,4-dimethoxybenzoic acid(22),gallic acid(23),dibutylphthalate(24),bis-(2-ethylhexyl)phthalate(25),9-nonadecenoic acid(26),triacylglycerol(27),crocin Ⅰ(28).The IC50 values of compound 1 for human gastric adenocarcinoma cells BGC-823 and human colon cancer cells HCT-116 were(22.07±0.38),(20.67±0.11)μmol/L,respectively.The IC50 value of compound 9 for BGC-823 cells was(21.58±0.05)μmol/L,and the IC50 value of compound 4 for HCT-116 cells was(16.67±0.36)μmol/L.CONCLUSION Compounds 1-10,14-15 and 28 are first isolated from Tetrastigma genus.Compounds 1,4,9 have weak antitumor activity in vitro.