OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

BACKGROUND:Sarcopenia is an age-related systemic skeletal muscle disease,which is associated with a variety of adverse outcomes such as falls,functional decline,frailty,and death.Postmenopausal women are one of the high-risk groups for sarcopenia.OBJECTIVE:To develop a predictive model for assessing the risk of sarcopenia in Chinese postmenopausal women based on high-quality database.METHODS:Data for this study were derived from 2 370 postmenopausal women from the China Health and Retirement Longitudinal Study(CHARLS),and sarcopenia was assessed using the Asian Working Group on Sarcopenia 2019(AWGS2019)recommended metrics.The study cohort was randomized into a training set(70％)and a validation set(30％).Risk factors for sarcopenia in postmenopausal women were screened using the least absolute shrinkage and selection operator,ten-fold cross-validation,and logistic regression.Nomogram predicting the risk of sarcopenia in postmenopausal women was constructed based on the risk factors,and the model efficacy was evaluated by the receiver operating characteristic curve and area under the curve(AUC),calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:The prevalence of sarcopenia in this study was 23.50％and age,place of residence,sleep quality,cognitive function,depression,and the number of chronic diseases were selected as predictors of sarcopenia in postmenopausal women.The nomogram model showed good discrimination between the training and validation sets,with an AUC value of 0.751(95％confidence interval=0.724-0.778,P＜0.001),a specificity of 72.2％,and a sensitivity of 63.2％in the training set,and an AUC value of 0.763(95％confidence interval=0.721-0.805,P＜0.001),with a specificity of 69.6％and a sensitivity of 70.8％.The calibration curve showed a relatively significant agreement between the nomogram model and the actual observations,and the decision curve analysis demonstrated broad and good clinical utility.To conclude,the nomogram to assess the risk of sarcopenia constructed based on age,place of residence,sleep quality,cognitive function,depression,and number of chronic diseases,provides an effective tool for identifying and eliminating risk factors for sarcopenia in Chinese postmenopausal women,and helps to reduce the incidence of sarcopenia.

BACKGROUND:Sarcopenia is an age-related systemic skeletal muscle disease,which is associated with a variety of adverse outcomes such as falls,functional decline,frailty,and death.Postmenopausal women are one of the high-risk groups for sarcopenia.OBJECTIVE:To develop a predictive model for assessing the risk of sarcopenia in Chinese postmenopausal women based on high-quality database.METHODS:Data for this study were derived from 2 370 postmenopausal women from the China Health and Retirement Longitudinal Study(CHARLS),and sarcopenia was assessed using the Asian Working Group on Sarcopenia 2019(AWGS2019)recommended metrics.The study cohort was randomized into a training set(70％)and a validation set(30％).Risk factors for sarcopenia in postmenopausal women were screened using the least absolute shrinkage and selection operator,ten-fold cross-validation,and logistic regression.Nomogram predicting the risk of sarcopenia in postmenopausal women was constructed based on the risk factors,and the model efficacy was evaluated by the receiver operating characteristic curve and area under the curve(AUC),calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:The prevalence of sarcopenia in this study was 23.50％and age,place of residence,sleep quality,cognitive function,depression,and the number of chronic diseases were selected as predictors of sarcopenia in postmenopausal women.The nomogram model showed good discrimination between the training and validation sets,with an AUC value of 0.751(95％confidence interval=0.724-0.778,P＜0.001),a specificity of 72.2％,and a sensitivity of 63.2％in the training set,and an AUC value of 0.763(95％confidence interval=0.721-0.805,P＜0.001),with a specificity of 69.6％and a sensitivity of 70.8％.The calibration curve showed a relatively significant agreement between the nomogram model and the actual observations,and the decision curve analysis demonstrated broad and good clinical utility.To conclude,the nomogram to assess the risk of sarcopenia constructed based on age,place of residence,sleep quality,cognitive function,depression,and number of chronic diseases,provides an effective tool for identifying and eliminating risk factors for sarcopenia in Chinese postmenopausal women,and helps to reduce the incidence of sarcopenia.

ObjectiveTo evaluate the efficacy and possible mechanism of Wei's Huoxue Tongluo Formula （韦氏活血通络方，WHTF） in treating atrophic-stage non-arteritic anterior ischemic optic neuropathy （NAION） with qi deficiency and blood stasis. MethodsA total of 82 atrophic-stage NAION patients with qi deficiency and blood stasis were randomly divided into a treatment group and a control group， with 41 cases in each group. The treatment group was given oral administration of WHTF twice a day plus acupoint injection of distilled water 2 ml at Taiyang （EX-HN5） once daily， while the control group received injection of compound anisodine injection 2 ml at Taiyang （EX-HN5） once daily and oral administration of WHTF placebo twice a day. Both groups received treatment for a course of 14 days. The best-corrected visual acuity （BCVA）， optic disc perfusion density （PD）， flux index （FI）， macular superficial PD， vascular density （VD）， and traditional Chinese medicine （TCM） syndrome scores were compared between groups before treatment and on day 7 and day 14 of treatment. Additionally， mean defect （MD） and mean sensitivity （MS） of visual fields were measured before treatment and on day 14， along with safety evaluation. ResultsAfter treatment， both groups showed significant improvement in BCVA， visual field MD and MS， and TCM syndrome scores （P＜0.05 or P＜0.01）. On day 14 of treatment， the TCM syndrome score in the treatment group was significantly lower than that in the control group （P＜0.05）. There was no significant improvement in optic disc PD and FI， and macular superficial PD and VD after treatment in either group （P＞0.05） except that on day 7 the macular superficial foveal PD in the control group was significantly better than that in the treatment group （P＜0.05）. During the treatment period， no serious adverse events occurred in either group. ConclusionWHTF can improve the visual function indicators including visual acuity and visual field， as well as TCM syndrome scores in atrophic-stage NAION patients with qi deficiency and blood stasis. It shows clinical safety， although it does not appear to have a significant effect on optic disc or macular blood flow.

ObjectiveTo explore the inhibitory effect and related molecular mechanisms of Saponin of Schizocapsa plantaginea HanceⅠ （SSPHⅠ） on human nasopharyngeal carcinoma HONE-1 cells. MethodsThe effect of SSPHⅠ on HONE-1 cell viability was detected using the CCK-8 assay. Its inhibitory effect on cell proliferation was evaluated through a colony formation assay. Changes in cell invasion ability were analyzed using the Transwell assay. Intracellular reactive oxygen species （ROS） levels were measured using the DHE fluorescent probe. The extent of intracellular content release was reflected by the LDH release assay. The rate of cell pyroptosis was detected using the Annexin-V/PI double staining method. Changes in the expression of proteins related to the classical pyroptosis pathway were examined by Western Blot. ResultsCCK-8 assay showed that treatment with SSPHⅠ for 24 hours reduced HONE-1 cell viability in a concentration-dependent manner， with an IC50 value of 3.383 μmol/L. In the colony formation assay， the number of HONE-1 cell colonies gradually decreased with increasing concentrations of SSPHⅠ （P<0.01）. The Transwell assay revealed that the number of cells migrating through the chamber was reduced following SSPHⅠ treatment （P<0.01）. DHE fluorescence probe detection indicated that intracellular ROS fluorescence intensity increased after SSPHⅠ treatment （P<0.001）. The LDH release assay showed that LDH activity in the cell supernatant increased with higher concentrations of SSPHⅠ （P<0.001）. Annexin-V/PI double staining demonstrated that the proportion of Annexin-V/PI-positive cells increased after SSPHⅠ treatment （P<0.001）. Western blot analysis showed that， compared with the control group， the protein expression levels of cleaved-Caspase-1 and GSDMD-N-terminal were upregulated in SSPHⅠ-treated cells （P<0.05）， and NLRP3 protein expression levels also increased （P<0.05）. ELISA results showed that the levels of IL-1β and IL-18 in the cells increased with higher concentrations of SSPHⅠ （P<0.05）. ConclusionSSPHⅠ can induce pyroptosis in nasopharyngeal carcinoma HONE-1 cells by regulating the ROS/NLRP3/Caspase-1 signaling axis， thereby exerting an anti-nasopharyngeal carcinoma effect. This suggests that SSPHⅠ may serve as a potential therapeutic agent for nasopharyngeal carcinoma.

Background As one of the primary operational methods in the power grid industry, the insulated glove working method imposes significant physical demands due to the constraints of insulating equipment and specific required postures, resulting in substantial occupational health hazards among workers in this sector, which have garnered widespread social attention. Objective To investigate the prevalence and influencing factors of work-related musculoskeletal disorders (WMSDs) in the neck, shoulder, and lumbar regions among workers wearing insulated gloves, and to provide targeted measures to reduce occupational hazards. Methods Using stratified cluster sampling, 1079 frontline workers were randomly selected from power supply enterprises across 3 provinces in China. The revised Chinese version of the Musculoskeletal Disorders Questionnaire was used to investigate the 1-year prevalence of WMSDs in the neck, shoulder, and lumbar regions among workers wearing insulated gloves, and to collect factors associated with multi-site WMSDs (defined as involvement of ≥2 sites among the neck, shoulder, and lumbar). Results The 1-year prevalence of WMSDs in the neck, shoulder, and lumbar regions was 39.9%, 30.0%, and 25.3%, respectively, with a multi-site WMSDs prevalence of 32.0%. Multiple logistic regression analysis showed that, compared to workers with technical secondary school education or senior high school education and below, workers with junior college education or bachelor’s degrees and above had a higher risk of multi-site WMSDs (OR=2.12, 95%CI: 1.47, 3.06). Compared to workers with <10 years of work experience, those with 10-<20 years of work experience had a higher risk of multi-site WMSDs (OR=1.96, 95%CI: 1.45, 2.67). Working in uncomfortable postures "sometimes" (OR=1.64, 95%CI: 1.14, 2.36), "frequently" (OR=2.75, 95%CI: 1.76, 4.29), and "very frequently" (OR=3.55, 95%CI: 2.04, 6.19) were significantly associated with an increased risk of multi-site WMSDs compared to never working in such postures. Frequent repetitive movements of the low back (OR=2.05, 95%CI: 1.48, 2.84) increased the risk of multi-site WMSDs, while sufficient rest time decreased the risk (OR=0.45, 95%CI: 0.34, 0.61). Conclusion The prevalences of single-site and multi-site WMSDs in the neck, shoulder, lumbar regions are relatively high among workers wearing insulated gloves. Factors associated with multi-site WMSDs include 10-<20 years of work experience, junior college education or bachelor’s degrees and above, uncomfortable working postures, frequent repetitive low-back movements, and lack of sufficient rest time.

Background As one of the primary operational methods in the power grid industry, the insulated glove working method imposes significant physical demands due to the constraints of insulating equipment and specific required postures, resulting in substantial occupational health hazards among workers in this sector, which have garnered widespread social attention. Objective To investigate the prevalence and influencing factors of work-related musculoskeletal disorders (WMSDs) in the neck, shoulder, and lumbar regions among workers wearing insulated gloves, and to provide targeted measures to reduce occupational hazards. Methods Using stratified cluster sampling, 1079 frontline workers were randomly selected from power supply enterprises across 3 provinces in China. The revised Chinese version of the Musculoskeletal Disorders Questionnaire was used to investigate the 1-year prevalence of WMSDs in the neck, shoulder, and lumbar regions among workers wearing insulated gloves, and to collect factors associated with multi-site WMSDs (defined as involvement of ≥2 sites among the neck, shoulder, and lumbar). Results The 1-year prevalence of WMSDs in the neck, shoulder, and lumbar regions was 39.9%, 30.0%, and 25.3%, respectively, with a multi-site WMSDs prevalence of 32.0%. Multiple logistic regression analysis showed that, compared to workers with technical secondary school education or senior high school education and below, workers with junior college education or bachelor’s degrees and above had a higher risk of multi-site WMSDs (OR=2.12, 95%CI: 1.47, 3.06). Compared to workers with <10 years of work experience, those with 10-<20 years of work experience had a higher risk of multi-site WMSDs (OR=1.96, 95%CI: 1.45, 2.67). Working in uncomfortable postures "sometimes" (OR=1.64, 95%CI: 1.14, 2.36), "frequently" (OR=2.75, 95%CI: 1.76, 4.29), and "very frequently" (OR=3.55, 95%CI: 2.04, 6.19) were significantly associated with an increased risk of multi-site WMSDs compared to never working in such postures. Frequent repetitive movements of the low back (OR=2.05, 95%CI: 1.48, 2.84) increased the risk of multi-site WMSDs, while sufficient rest time decreased the risk (OR=0.45, 95%CI: 0.34, 0.61). Conclusion The prevalences of single-site and multi-site WMSDs in the neck, shoulder, lumbar regions are relatively high among workers wearing insulated gloves. Factors associated with multi-site WMSDs include 10-<20 years of work experience, junior college education or bachelor’s degrees and above, uncomfortable working postures, frequent repetitive low-back movements, and lack of sufficient rest time.

Lentiviral vectors(LVs)are key gene delivery tools for integrating target genes into the host genome,but they may also pose risks of insertional mutagenesis.The vector copy number(VCN)in cells is critical for determining the safety of gene modification.However,the reliability and accuracy of its quantification process are influenced by multiple factors.Developing cell reference materials with specific vector copy numbers represents a viable approach to enhance the reliability and consistency of measurement results,enabling quality control of the quantification process and traceability of outcomes.However,the preparation of such reference materials faces challenges in cell sample design,preparation protocols,and advanced quantification techniques.In this study,T lymphocyte cell line Jurkat-based reference materials with LV gene copy numbers of 1 and 2 copy/cell were developed.A high-precision duplex digital polymerase chain reaction(dPCR)method was established to quantify the LV gene and endogenous genes simultaneously.Additionally,the results of dPCR were cross-validated through next-generation sequencing and flow cytometric analysis.Ultimately,confocal microscopy characterization results showed that the developed cell reference materials had intact morphology.The quantification result of VCN-1 was(1.07±0.11)copy/cell,and that of VCN-2 was(2.09±0.21)copy/cell.These cell reference materials demonstrated compliance with stability and homogeneity requirements,and could be applied for quality control throughout the VCN measurement workflow and metrological traceability,improving the accuracy,comparability,and validity of copy number measurements.

Objective To explore the mechanism of myocardial toxicity caused by N-methyl-3,4-methyle-nedioxyamphetamine(MDMA),the changes of intracellular calcium oscillation mode and calcium han-dling proteins during acute exposure to different concentrations of MDMA were detected,and the in-volvement of nuclear factor κB(NF-κB)and its effect on calcium handling proteins were investigated.Methods Primary rat cardiomyocytes were cultured to establish MDMA acute exposure model,and a control group was set up.The MDMA poisoning model was divided into three concentration groups of 10,100 and 1 000 μmol/L.After 1 h of exposure,the morphological changes of cardiomyocytes were ob-served,the cytotoxicity and changes in calcium signals were measured,and the changes in calcium handling proteins RyR2,SERCA2a,PLN,NCX1 and Cav1.2 were detected.The changes of NF-κB activity and the expression of nucleoprotein p-p65(Ser311)and PKCζ after MDMA exposure,and the intervention of NF-κB inhibitors pyrrolidine dithiocarbamate ammonium(PDTC)and protein kinase C(PKC)inhibitor chelerythrine(CHE)were detected by electrophoretic mobility shift assay(EMSA)and Western blotting.The effects of PDTC intervention on calcium signals,and the expressions of RyR2,SERCA2a,PLN,NCX1 and Cav1.2 after acute MDMA exposure were also observed.Results No obvious changes were observed in the morphology of cardiomyocytes after acute exposure to MDMA,whereas the oscillation waveform of intracytoplasmic calcium ion showed irregular changes with increased oscillation amplitude,intense fluctuations,irregular frequency,and increased fluctuation range of relative optical density values.The expression of RyR2,SERCA2a and NCX1 increased,while the expression of Cav1.2 and PLN de-creased.Acute MDMA exposure could increase NF-κB activity,while PDTC and CHE intervention could inhibit NF-κB activity.In MDMA exposed group,the expression of PKCζ and nucleoprotein p-p65(Ser311)both increased and could be inhibited by CHE.After the intervention of PDTC to block NF-κB,the amplitude of calcium oscillation was lower than that of the MDMA exposed group,and the expres-sion of RyR2,SERCA2a and NCX1 decreased.There was no significant change in PLN,while the ex-pression of Cav1.2 increased.Conclusion MDMA can lead to an increase of calcium ion concentration in cardiomyocytes.Calcium ions are involved in myocardial toxicity of MDMA.The mechanism is re-lated to changes in calcium handling proteins,mainly associated with the increased expression of RyR2.MDMA can up-regulate the intracellular activity of NF-κB through the PKCζ-NF-κB pathway and affect calcium handling proteins,which aggravate intracellular calcium overload during acute MDMA exposure.

Objective:To explore the effects of Jianpi Mixture on the glucose receptor/glucagon like peptide-1 (GLP-1)/5-hydroxytryptamine (5-HT) signaling pathway and the mechanism of Jianpi Mixture in improving visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome (IBS-D) rats.Methods:Totally 40 healthy male SPF rats were divided into blank group, model group, Jianpi Mixture low- and high-dosage groups according to the random number table method, with 10 rats in each group. Except for the blank group, the rest of the rats were prepared by the "senna gavage combined with restraint stress" method to replicate the IBS-D spleen deficiency model. The aqueous extract of Jianpi Mixture was 2.52 and 7.56 g/kg in the low- and high-dosage groups, and the same volume of normal saline was given to the blank group and the model group, once a day, for 14 days. On the 1st, 7th and 14th days of administration, the body weight of rats was recorded, the fecal traits of the rats were scored with Bristol score, the visceral sensitivity of IBS-D rats was evaluated by the abdominal wall retraction reflex score (AWR) under rectal dilation, the morphology of colonic mucosal tissues was observed by HE staining, and the protein expressions of T1R2, SLGT1, GLUT2, GLP-1 and 5-HT in colon tissues were detected by immunohistochemical staining.Results:On the 1st, 7th and 14th days of administration, compared with the model group, the weight of the rats in the Jianpi Mixture high-dosage group increased ( P<0.05); on the 14th day of administration, the fecal Bristol score decreased significantly ( P<0.05) and the AWR score increased ( P<0.05); HE staining showed that the mucosal epithelium of colon tissue in the model group was slightly damaged, and local edema was visible. The pathological condition of colonic mucosa in the Jianpi Mixture low- and high-dosage groups was effectively improved; compared with the model group, the expressions of T1R2 and GLP-1 in the Jianpi Mixture low- and high-dosage groups increased ( P<0.05), and the expression of 5-HT decreased ( P<0.05); the protein expressions of GLUT2 and SGLT1 in the Jianpi Mixture high-dosage group increased ( P<0.05). Conclusion:Jianpi Mixture can treat spleen-deficiency IBS-D by restoring the normal expression of intestinal glucose receptors, regulating the secretion of GLP-1/5-HT, improving intestinal motility and alleviating visceral hypersensitivity.