ObjectiveTo observe the clinical efficacy and safety of Huatan Quyu formula in treating cerebral small vessel disease （CSVD） with phlegm and blood stasis blocking collateral pattern via randomized controlled trial， and explore its mechanism of improving CSVD by regulating glymphatic system （GS） circulation. MethodsSixty-eight CSVD patients with phlegm and blood stasis blocking collateral pattern in the Department of Encephalopathy， Affiliated Hospital of Shaanxi University of Chinese Medicine from April to December 2024 were selected and randomly divided into an experimental group （34 cases） and a control group， with 34 cases in each group. Both groups received basic Western medicine treatment， while the experimental group additionally received Huatan Quyu formula. After a course of 12 weeks， the following parameters were compared between the two groups before and after treatment. Clinical outcomes were assessed using the Tinetti performance-oriented mobility assessment （POMA）， Montreal Cognitive Assessment （MoCA）， Scales for Outcomes in Parkinson's Disease-Autonomic （SCOPA-AUT）， and traditional Chinese medicine （TCM） syndrome scores of phlegm and blood stasis blocking collateral pattern. Perivascular space （PVS） in the frontal lobe/basal ganglia and cerebrospinal fluid （CSF） flow parameters in the cerebral aqueduct were evaluated by 3.0T brain MRI， cerebrospinal fluid flow imaging， and phase-contrast magnetic resonance imaging （PC-MRI）. Then， safety indicators were monitored， and SPSS 25.0 was used for statistical analysis. ResultsSixty-four patients completed the study （32 in each group）. ①Baseline data： No statistically significant difference was found between the two group. ②Efficacy indicators： After treatment， the experimental group exhibited significantly improved total POMA， SCOPA-AUT， and TCM syndrome scores （P<0.01）， outperforming the control group （P<0.05）. No significant change was observed in MoCA scores between the two groups. ③Imaging indicators： The experimental group showed a reduced PVS area alongside significantly increased CSF flow parameters （including downward flow during the systolic period， and upward flow during the diastolic period） （P<0.01）， which were superior to the control group （P<0.01）. ④Safety： The laboratory indicators were normal in both groups， with no drug-related adverse reactions. ConclusionFor CSVD patients with phlegm and blood stasis blocking collateral pattern， Huatan Quyu formula can safely and effectively improve motor function， autonomic nerve function， and TCM syndromes， with potential mechanisms related to pulsatile CSF flow enhancement and GS circulation efficiency improvement.

Objective: To develop a prediction model for mild cognitive impairment (MCI) risk among the elderly, so as to provide a tool for MCI early screening. Methods : From July 2022 to September 2024, a multi-stage stratified random cluster sampling method was used to recruit permanent residents aged ≥65 years from the Xinjiang Uygur Autonomous Region as study participants. Data on sociodemographic characteristics, nutritional status, body composition indices, bone mineral density, and handgrip strength were collected through questionnaires and physical examinations. Sarcopenia was defined based on appendicular skeletal muscle index and handgrip strength. MCI was assessed using the Mini-Mental State Examination, with adjustments for educational level. Participants were randomly divided into a training set and a validation set in a 7∶3 ratio. LASSO regression and multivariable logistic regression models were employed to screen for predictors and construct an MCI risk prediction model. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 1 641 participants were surveyed, including 755 males (46.01%) and 886 females (53.99%). The majority of participants were aged 65-<75 years, comprising 1 154 individuals (70.32%). MCI was detected in 517 participants, corresponding to a detection rate of 31.51%. Resultsfrom LASSO regression and multivariate logistic regression analysis showed that residence (rural, OR = 2.323, 95% CI: 1.682-3.210), age (75-<85 years, OR = 1.405, 95% CI: 1.019-1.937; ≥85 years, OR = 3.655, 95% CI: 1.696-7.875), educational level (primary school, OR = 0.341, 95% CI: 0.247-0.472; junior high school, OR = 0.255, 95% CI: 0.160-0.408; high school, OR = 0.286, 95% CI: 0.154-0.531; bachelor's degree or above, OR = 0.120, 95% CI: 0.041-0.351), history of alcohol consumption (yes, OR = 3.216, 95% CI: 2.164-4.779), risk of malnutrition (yes, OR = 1.464, 95% CI: 1.064-2.014), sarcopenia (yes, OR = 3.197, 95% CI: 2.332-4.385), and waist-to-hip ratio (abnormal, OR = 1.540, 95% CI: 1.159-2.048) were identified as predictive factors for MCI among the elderly. In the training set, the area under the ROC curve, sensitivity, and specificity were 0.788, 0.719, and 0.712, respectively. In the validation set, the corresponding values were 0.784, 0.913, and 0.542, respectively. DCA demonstrated that the model provided a higher clinical net benefit for predicting MCI risk when the risk threshold probability ranged from 0.124 to 0.764. Conclusion The prediction model developed in this study demonstrates good discriminative ability and clinical utility, indicating its substantial value for predicting the MCI risk among the elderly.

Objective To analyze the monitoring data of ¹³¹I internal exposure in Guangdong Province over the past 3 years, study the thyroid ¹³¹I contamination levels among nuclear medicine staff, and provide a basis for optimizing the monitoring plan. Methods Using a convenience sampling method, 574 detections of nuclear medicine staff from 28 hospitals in Guangdong Province were included in the study. The thyroid ¹³¹I activity was measured directly in vivo. Differences in detection rates were analyzed, and committed effective doses were estimated. Results Over the past 3 years in Guangdong Province, ¹³¹I accumulation was found in the thyroids of staff from 14 hospitals for 62 (10.8%) detections, with an average activity of 154.8 (13.2-8730.6) Bq. The adjusted annual intake was 50.7 (4.5-820.6) kBq. The committed effective dose was 0.56 (0.05-9.03) mSv/a, and the values were ≥ 2 mSv for 8 persons. Among different positions, nurses showed the highest detection rate (19.6%), followed by cleaners (14.7%), with significant differences (P<0.05). Among different exposure types, the detection rate was highest for loading medication into automatic dispenser (23.3%), and the mean activity was highest for entering thyroid cancer patient ward (495.4 Bq), with significant differences (P<0.05). Conclusion Monitoring of ¹³¹I internal exposure in Guangdong Province found that the radiation doses of some staff members had exceeded the threshold specified in other investigations. Routine personal ¹³¹I internal exposure monitoring should be conducted, with increased monitoring frequency. Priority should be given to nurses and cleaners, with monitoring extended to cleaners and outsourced dispensing staff.

Objective To construct the K64 capsule depolymerase recombinant protein,Dep44,and investigate its potential application against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Methods The de-polymerase-encoding phage vB_Kpn_HF1013(GenBank:PP803128)was isolated and genomically analyzed to screen for candidate depolymerases.The recombinant protein Dep44 was constructed and functionally verified for depolymerase activity.Dep44 sensitive range was validated and Dep44 antimicrobial activity was assessed by bio-film disruption and serum sterilization assays.Results The tail spike protein of phage vB_Kpn_HF1013 exhibited depolymerase activity and recombinant protein Dep44 specifically degraded K64 CRKP capsule.Biofilm eradication assays demonstrated that recombinant Dep44 at both 2 μg/mL and 10 μg/mL significantly disrupted bacterial bio-films relative to the control.Serum bactericidal assays showed that Dep44 exhibited synergistic activity with serum,dependent on the complement system,as Dep44 alone lacked bactericidal properties.Conclusion Dep44 effec-tively targets and degrades K64 CRKP capsule,disrupts biofilms,and enhances serum bactericidal activity,high-lighting its potential for managing K64 CRKP infections and clearing biofilms from medical devices.

AIM To observe the effects of Yiqi Jiedu Tongluo Formula(YQJDTL)on renal microvascular endothelial function and prevention of renal injury in a rat model of type 2 diabetes mellitus(T2DM).METHODS The SD rats were randomly divided into a normal group and a model group.The model group was administered with high-fat diet combined with a single intraperitoneal injection of STZ to establish the T2DM model.The successfully modeled rats were randomly divided into the model group,the canagliflozin group(9 mg/kg),and the low-dose and high-dose YQJDTL groups(4.77,9.45 g/kg).The corresponding doses of the drug were administered by gavage for a total of 12 weeks,during which the rats underwent observation of their general condition and blood glucose changes.After the end of administration,the rats had their levels of renal index,24-hour UP,serum SCr,BUN,TC,TG,HDL-C,LDL-C,ET-1 and NOS measured;their changes in renal microvasculature and the degree of renal fibrosis observed using HE staining,Masson staining,PAS staining,and PASM staining;their ultrastructure of the glomeruli observed using transmission electron microscopy;their renal protein expressions of TGF-β,SMAD2,SMAD3,Col-1,VEGFA and PKC detected by immunohistochemical staining and Western blot;and their renal mRNA expressions of VEGFA,TGF-β,SMAD2 determined by RT-qPCR.RESULTS Compared with the model group,the high-dose YQJDTL group showed decreased levels of renal index,blood glucose,TG,TC,HDL,24 h UP,BUN,SCr and ET-1(P＜0.05,P＜0.01);increased LDL and NOS levels(P＜0.05,P＜0.01);reduced renal inflammatory infiltration and fibrosis degree,inhibited fusion of foot processes and thickening of basement membrane;decreased renal protein expressions of TGF-β,SMAD2,SMAD3,VEGFA,PKC and Col-1(P＜0.05,P＜0.01);and decreased mRNA expressions of VEGFA,TGF-β and SMAD2(P＜0.01).CONCLUSION In the rat models of T2DM,YQJDTL can reduce their levels of blood glucose and lipids by improving the renal indices levels and the renal microvascular endothelial functions to alleviate renal fibrosis and microangiopathy as well,and the mechanism may be associated with the down-regulated expressions of TGF-β/SMAD and VEGF pathway-related proteins.

Objective:To analyze the evolution of ceftazidime/avibactam (CZA) resistance phenotyes and clinical features of 11 ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates carrying bla KPC. Methods:Eleven CRKP isolates, designated K01 to K11, obtained from infected liver transplant patients from June to September 2024 were retrospectively studied. Broth microdilution method, whole genome sequencing (WGS) and plasmid conjugation assays were employed to investigate the antimicrobial susceptibility, resistance mechanisms, and genetic structural characteristics of these CRKP isolates. Clinical data were simultaneously collected and organized to analyze the correlation between bla KPC gene mutations and the clinical efficacy of antimicrobial therapy. Results:All eleven isolates of CRKP exhibited multidrug resistance phenotypes. Among them, K01-K09 and K11 were sensitive to CZA and resistant to carbapenems, while K10 was resistant to CZA and displayed sensitivity or intermediate resistance to carbapenems. WGS analysis showed that all 11 CRKP isolates belonged to the ST11-KL64 clonal type. Among these isolates, the K01-K09 and K11 isolates carry the bla KPC-2 gene, whereas the K10 isolate carries the bla KPC-33 gene. A single nucleotide mutation in bla KPC-2 (G532T) resulted in a substitution of tyrosine (Y) for aspartic acid (D) at Ambler position 179 (D179Y), causing resistance of CRKP to CZA and reduced sensitivity to Imipenem and Meropenem. The conjugative plasmid was successfully constructed, and compared to the parental strain, its minimum inhibitory concentration (MIC) to CZA increased 32 folds. Clinical data revealed that the patient developed the bla KPC-33 mutation after 51 days of CZA treatment. Conclusions:The bla KPC-33 mutation following CZA treatment for CRKP infection exhibits a considerable delay. It is essential to dynamically monitor the evolution of CRKP resistance to ensure timely adjustment of therapeutic strategies in case of the occurrence of mutations such as bla KPC-33.

Objective To construct the K64 capsule depolymerase recombinant protein,Dep44,and investigate its potential application against carbapenem-resistant Klebsiella pneumoniae(CRKP)infections.Methods The de-polymerase-encoding phage vB_Kpn_HF1013(GenBank:PP803128)was isolated and genomically analyzed to screen for candidate depolymerases.The recombinant protein Dep44 was constructed and functionally verified for depolymerase activity.Dep44 sensitive range was validated and Dep44 antimicrobial activity was assessed by bio-film disruption and serum sterilization assays.Results The tail spike protein of phage vB_Kpn_HF1013 exhibited depolymerase activity and recombinant protein Dep44 specifically degraded K64 CRKP capsule.Biofilm eradication assays demonstrated that recombinant Dep44 at both 2 μg/mL and 10 μg/mL significantly disrupted bacterial bio-films relative to the control.Serum bactericidal assays showed that Dep44 exhibited synergistic activity with serum,dependent on the complement system,as Dep44 alone lacked bactericidal properties.Conclusion Dep44 effec-tively targets and degrades K64 CRKP capsule,disrupts biofilms,and enhances serum bactericidal activity,high-lighting its potential for managing K64 CRKP infections and clearing biofilms from medical devices.

Objective:To analyze the synergistic relationship between financing and payment systems in China's urban employee basic medical insurance under the background of aging,providing decision-making basis for promoting coordinated development of these two systems.Methods:Based on statistical yearbook data from medical security systems,the Delphi method was employed to identify collaborative analysis indicators for urban employee medical insurance financing and payment under the aging population context.A collaborative theory-based model was constructed to measure the coordination degree of China's urban employee medical insurance financing and payment composite system,while simultaneously assessing the orderliness of the financing and payment system and the coordination degree of the composite system.Results:The order degree of the financing system ranged from 0.324 in 2019 to 0.517 in 2023;the order degree of the payment system ranged from 0.454 in 2019 to 0.517 in 2023;the synergy degree of both systems reached-0.084 in 2023.Conclusions:Influenced by aging,the development speed and scale of China's urban employee basic medical insurance financing system and payment system are asynchronous,with the payment system being more affected than the financing system,resulting in a non-coordinated and disordered development state of the composite financing-payment system.

AIM To observe the effects of Yiqi Jiedu Tongluo Formula(YQJDTL)on renal microvascular endothelial function and prevention of renal injury in a rat model of type 2 diabetes mellitus(T2DM).METHODS The SD rats were randomly divided into a normal group and a model group.The model group was administered with high-fat diet combined with a single intraperitoneal injection of STZ to establish the T2DM model.The successfully modeled rats were randomly divided into the model group,the canagliflozin group(9 mg/kg),and the low-dose and high-dose YQJDTL groups(4.77,9.45 g/kg).The corresponding doses of the drug were administered by gavage for a total of 12 weeks,during which the rats underwent observation of their general condition and blood glucose changes.After the end of administration,the rats had their levels of renal index,24-hour UP,serum SCr,BUN,TC,TG,HDL-C,LDL-C,ET-1 and NOS measured;their changes in renal microvasculature and the degree of renal fibrosis observed using HE staining,Masson staining,PAS staining,and PASM staining;their ultrastructure of the glomeruli observed using transmission electron microscopy;their renal protein expressions of TGF-β,SMAD2,SMAD3,Col-1,VEGFA and PKC detected by immunohistochemical staining and Western blot;and their renal mRNA expressions of VEGFA,TGF-β,SMAD2 determined by RT-qPCR.RESULTS Compared with the model group,the high-dose YQJDTL group showed decreased levels of renal index,blood glucose,TG,TC,HDL,24 h UP,BUN,SCr and ET-1(P＜0.05,P＜0.01);increased LDL and NOS levels(P＜0.05,P＜0.01);reduced renal inflammatory infiltration and fibrosis degree,inhibited fusion of foot processes and thickening of basement membrane;decreased renal protein expressions of TGF-β,SMAD2,SMAD3,VEGFA,PKC and Col-1(P＜0.05,P＜0.01);and decreased mRNA expressions of VEGFA,TGF-β and SMAD2(P＜0.01).CONCLUSION In the rat models of T2DM,YQJDTL can reduce their levels of blood glucose and lipids by improving the renal indices levels and the renal microvascular endothelial functions to alleviate renal fibrosis and microangiopathy as well,and the mechanism may be associated with the down-regulated expressions of TGF-β/SMAD and VEGF pathway-related proteins.

Polycystic ovary syndrome （PCOS） is one of the most prevalent gynecological diseases， and its incidence is increasing year by year， seriously affecting the physical and mental health of female patients. The pathogenesis of this disease is complex and has not been fully clarified. At present， PCOS is mainly treated by Western medicine， which， however， has poor efficacy and induces various adverse reactions. Therefore， developing safe and effective therapies has become a difficult problem that needs to be solved. Studies have confirmed that traditional Chinese medicine （TCM） can regulate phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， mitogen-activated protein kinase/extracellular signal-regulated kinase （MAPK/ERK）， Toll-like receptor 4/nuclear factor-κB （TLR4/NF-κB）， transforming growth factor-β （TGF-β）/Smads， secreted glycoprotein/β-catenin （Wnt/β-catenin）， adenosine monophosphate-activated protein kinase （AMPK）， and advanced glycation endproduct/receptor for advanced glycation endproducts （AGE/RAGE） signaling pathways to ameliorate insulin resistance， inhibit inflammation and oxidative stress， regulate endocrine hormone disorders， and intervene in apoptosis and autophagy， thus alleviating the symptoms， slowing down the disease progression， and improving the ovarian function. The treatment of PCOS with TCM has demonstrated definite effects and high safety. Therefore， exploring this disease from cellular and molecular perspectives can provide a theoretical basis for its clinical treatment and new drug development. However， there is a lack of systematic reviews on the modulation of relevant signaling pathways by TCM in the treatment of PCOS. This article reviews the research progress in the treatment of PCOS with the active ingredients and compound prescriptions of TCM by regulating relevant signaling pathways in recent years， with the aim of providing evidence to support the promotion of TCM for treating PCOS in the future.