OBJECTIVE To evaluate the therapeutic efficacy of 5 regimens of colistin sulfate for common Gram-negative bacilli infection based on pharmacokinetics （PK）/pharmacodynamics （PD） theory and Monte Carlo simulation. METHODS Minimal inhibitory concentration （MIC） data of colistin sulfate against Acinetobacter baumannii， Pseudomonas aeruginosa， Klebsiella pneumoniae， Escherichia coli and Enterobacter cloacae in 2023 were collected from the China Antimicrobial Resistance Surveillance System. Monte Carlo simulation was conducted with the ratio of the area under the concentration-time curve from 0 to 24 hours in the unbound state to the MIC （fAUC0－24 h/MIC） ≥15 as the target value， the probabilities of target attainment （PTA） of 5 regimens of colistin sulfate to achieve the target ratio were obtained at different MIC； and the expected population PTA， specifically the cumulative fraction of response （CFR）， for each regimen within a specific bacterial population was further calculated， to evaluate the therapeutic efficacy of the five colistin sulfate regimens. RESULTS When bacterial MIC≤0.5 µg/mL， PTA of all colistin sulfate regimens （500 000 IU， q12 h； 500 000 IU， q8 h； 750 000 IU， q12 h； 750 000 IU， q8 h； 1 000 000 IU， q12 h） were all more than 90%. When bacterial MIC＝1 µg/mL， PTA for regimen （750 000 IU， q8 h） against A. baumannii， K. pneumoniae， P. aeruginosa， E. coli and E. cloacae， and for regimen （1 000 000 IU， q12 h） against the other four bacterial species （excluding P. aeruginosa） remained above 90%. When bacterial MIC≥2 µg/mL， PTA of 5 colistin sulfate regimens were all lower than 90%. For E. coli， the CFR of only colistin sulfate regimen （500 000 IU， q12 h） was less than 90%； for K. pneumoniae， the CFR of only colistin sulfate regimen （750 000 IU， q8 h and 1 000 000 IU， q12 h） was greater than 90%； for the other three bacteria， CFR of 5 regimens were all less than 90%. CONCLUSIONS When the MIC of Gram-negative bacteria is less than 0.5 µg/mL， colistin sulfate regimen with a routine dose can be selected for treatment. When MIC was 1 µg/mL， an increase in the dosing amount or frequency is required. The empirical treatment of the other four bacterial infections excluding E. coli requires the use of off-label doses.

ObjectiveTo investigate the incidence rate of primary liver cancer （PLC） and the progression of liver fibrosis in chronic hepatitis B （CHB） patients with low-level viremia （LLV） （HBV DNA<2 000 IU/mL but ≥20 IU/mL） after treatment adjustment， and to provide more robust evidence for clinical practice. MethodsA retrospective analysis was performed for the clinical data of LLV patients who initially received nucleos（t）ide analogue （NAs） for at least 48 weeks at the Fifth Medical Center of PLA General Hospital from August 2007 to April 2017 and subsequently underwent NAs adjustment due to LLV， and according to the virologic response after 48 weeks of treatment adjustment， the patients were divided into LLV group and complete virological response （CVR） group （HBV DNA<20 IU/mL）. The patients were followed up once every 3‍ ‍—‍ ‍6 months till the primary endpoint event of PLC or October 2024. The incidence rate of PLC and the progression of liver fibrosis were observed， and the progression of liver fibrosis was defined as an increase of ≥1 grade in fibrosis-4 （FIB-4） index. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups； the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate the cumulative incidence rate of PLC， and the Log-rank test was used for comparison between groups； the Cox regression analysis was used to investigate the risk factors for PLC， and the Logistic regression analysis was used to investigate the influencing factors for the progression of liver fibrosis. ResultsA total of 307 patients were enrolled， with a mean age of 50.0 years， and the male patients accounted for 80.5%. After 48 weeks of treatment with the adjusted NAs regimen， 254 patients （82.7%） achieved CVR， and 53 patients （17.3%） still had LLV. For the LLV group， the incidence rate of PLC was 30.2% and the rate of liver fibrosis progression was 22.6%， while for the CVR group， the incidence rate of PLC was only 13.4%， and the rate of liver fibrosis progression was 7.5%. The multivariate regression analyses showed that LLV was an independent risk factor for the onset of PLC （hazard ratio=2.623， 95% confidence interval ［CI］： 1.315‍ ‍—‍ ‍5.234， P=0.006） and the progression of liver fibrosis （odds ratio=3.213， 95%CI： 1.385‍ ‍—‍ ‍7.455， P=0.007）. ConclusionActive adjustment of treatment is needed immediately after the diagnosis of LLV to improve CVR， and if LLV persists after treatment adjustment， it is necessary to enhance the monitoring of liver fibrosis progression and PLC， so as to facilitate early diagnosis and treatment.

AIM:To investigate the effect of 3% diquafosol sodium eye drops on tear film homeostasis in patients wearing overnight orthokeratology lenses.METHODS:Retrospective study. A total of 340 patients(564 eyes)fitted with night-worn orthokeratology lenses from June to December 2022 were respectively divided into a diquafosol sodium group(200 cases, 323 eyes, treated with 3% diquafosol sodium eye drops)and a sodium hyaluronate group(140 cases, 241 eyes, treated with sodium hyaluronate eye drops). The uncorrected visual acuity(LogMAR), ocular surface disease index(OSDI), non-invasive tear film break-up time(NIBUT), meibomian gland infrared imaging score, and corneal epithelial fluorescein staining were analyzed and compared between the two groups.RESULTS:Compared to baseline, both groups showed significant improvements in uncorrected visual acuity(LogMAR)at 1 wk, 1, and 3 mo after lens wear(all P<0.01). However, no statistically significant difference in uncorrected visual acuity(LogMAR)was observed between the two groups at any time point(all P>0.05). No significant differences in NIBUT or OSDI scores were found between the groups before and at 1 wk after lens wear(all P>0.05). At the 1- and 3 mo follow-ups, the 3% diquafosol sodium group demonstrated significantly longer NIBUT(all P<0.001)and lower OSDI scores(all P<0.001)compared to the sodium hyaluronate group. After wearing lens for 3 mo, the meibomian gland infrared imaging scores were significantly better in the diquafosol sodium group(P<0.001), whereas no significant intergroup difference was observed in corneal fluorescein staining(P>0.05). Furthermore, the incidence of adverse events during the study period did not differ significantly between the two groups(P>0.05).CONCLUSION:Compared with sodium hyaluronate, 3% diquafosol sodium eye drops were more effective in maintaining tear film homeostasis in patients wearing overnight orthokeratology lenses.

Objective To study the spatial distribution of the incidence of pulmonary tuberculosis in Hubei Province and its influencing factors, so as to improve the theoretical basis for scientific development of tuberculosis prevention and control measures in the future. Methods The data of reported incidence of tuberculosis and related influencing factors in various counties and districts of Hubei Province in 2020 were collected. Global Moran's I index, hotspot analysis and geographically weighted regression (GWR) model analysis were used to calculate the spatial autocorrelation of the incidence of tuberculosis, and to analyze the influencing factors affecting the incidence rate of tuberculosis. Results There were obvious regional differences in the space distribution of the incidence rate of tuberculosis. Hot spot analysis showed positive spatial correlation and obvious clustering. The GWR model (AICc=784.251) in this study had higher AICc value compared to the ordinary least squares regression (OLS) model (AICc=804.2585). The GWR model showed that the increase in the proportion of the population aged 65 and above and the proportion of the ethnic minority population had a significant promoting effect on the increase of the incidence rate of tuberculosis, and there was significant spatial heterogeneity. The effect of PM_2.5 concentration on the incidence rate of pulmonary tuberculosis varied in different regions, and the degree of effect was also different. Conclusion The proportion of people aged 65 and above and the proportion of ethnic minorities may significantly influence the incidence of pulmonary tuberculosis. The effect of PM_2.5 concentration varies in different regions, so targeted measures should be formulated according to the situation in different regions.

Sesquiterpenoids are natural compounds composed of 15 carbon atoms， which can be divided into sesquiterpene alcohols， ketones， lactones， aldehydes， and carboxylic acids according to oxygen groups. These compounds are widely distributed in nature， and their physiological activities are diverse. For example， many sesquiterpenes with potential anticancer effects have been found for anti-tumor effects， including cytotoxicity， antioxidant， immune regulation， cell proliferation， and so on. In addition， some sesquiterpenoids have good application prospects in antibacterial， anti-inflammatory， and anti-cardiovascular diseases. Malignant tumors， inflammation， bacterial diseases， and cardiovascular diseases are the main diseases that cause human death， and natural products have unique advantages in the treatment of these diseases. Therefore， the development of new drugs that are easy to promote has become a new research hotspot. In this paper， the sesquiterpenes extracted from the natural components of Chinese herbs and plants with anti-tumor， anti-inflammatory， antibacterial， and anti-cardiovascular activities， such as Xanthium， Atractylodes， Convolvulus， Acanthium， Ligularia， Artemisia， Ligularia， Ligularia， Labiaceae Mint， Acanthophyllum， Turmeria， Ginger， and other Chinese herbs and plants， were discussed. The biological activities and related mechanisms of this compound were reviewed， which provided a reference for further research and clinical application of sesquiterpenes.

Objective To conduct an epidemiological survey of common congenital heart disease(CHD)among children in ethnic minority areas in southeastern Guizhou and to explore the influencing factors of delayed medical treatment.Methods From January 2019 to July 2022,18 850 children aged 3 months to 14 years in Qiandongnan Miao and Dong Autonomous Prefecture were selected;105 children with CHD were included in the training set,and they were divided into delayed group(80 cases)and non-delayed group(25 cases)according to whether or not to delay medical treatment.In addition,children with CHD(35 cases)from July 2022 to December 2022 were included in the validation set.The general data of the subjects in the two groups were compared and ana-lyzed.Multivariate logistic regression was performed and risk scoring model was constructed.Results The preva-lence of CHD in 18 850 children was 5.57‰(105/18 850),with the highest prevalence in Liping County,and the lowest in Huangping County.The proportion of children with secondary atrial septal defect was the highest,and that of the aortic valve malformation was the lowest.Among the complex cases of CHD,the proportion of children with single type was the highest,and that of children with three or more types were the lowest.Among children with CHD,the rate of delayed medical treatment was 76.19% (80/105).The median delay in medical treatment was 12 months,with an average of(18.78±4.77)months.Multifactor logistic regression analysis showed that heart murmur(level 2～3),less-educated(primary and secondary school)guardian,family per capita income<2 000 yuan,and frequent drinking of the guardian were independent risk factors for delayed medical treatment(P<0.05),and commercial settlement of medical expenses was independent protective factor(P<0.05).Risk scoring model divided the children into three groups:low risk(≤80 points),medium risk(>80 points and≤134 points)and high(>134 points)risk group.The evaluation of the model show that it was accurate,effective,safe,and reliable.Conclusion The highest prevalence is observed in Liping County.The proportion of children with secondary atrial septal defect and the proportion of children with single type are the highest.Delayed medical treat-ment is found in most of the children with CHD.Cardiac murmur,education background of the guardian,per capita family income,guardian alcohol consumption,and medical expense settlement method are all independent influencing factors for delayed medical treatment.

BACKGROUND:After the internal fixation of cannulated screws in femoral neck fractures,because the affected limb is often unable to bear weight in the short term and the implants with high stiffness have a stress shielding effect on the fracture end,it is easy to cause osteoporosis of the affected limb and changes in the biomechanical distribution of the proximal femur,the incidence of osteonecrosis of the femoral head is high after surgery.At present,few studies have been conducted on the biomechanical effects of osteoporosis at the proximal end of the femur occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws. OBJECTIVE:Using finite element analysis,to investigate the biomechanical effects of osteoporosis occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws and explore the role of biomechanical factors in osteonecrosis of the femoral head. METHODS:Based on the obtained CT scan data of the femur in a patient with a femoral neck fracture,a proximal femoral model for internal fixation for femoral neck fracture was established by Mimics 19.0,3-Matic,UG 11.0,Hypermesh 14.0,and Abaqus software.One finite element model of the proximal femur without osteoporosis and three finite element models of the proximal femur with osteoporosis were analyzed using Abaqus software.The stress,contact pressure,displacement peak and cloud map under different components of the four models were measured and analyzed,and the internal stress changes and distribution of the femoral head were compared and analyzed. RESULTS AND CONCLUSION:The stresses and contact pressures of the femoral head and lower anterior cannulated screws varied more with the degree of osteoporosis.The peak displacement of the four models increased slowly with the degree of osteoporosis.By one-way analysis of variance,there was no significant effect of the degree of osteoporosis on the peak stress,contact pressure,and displacement of the different components.The internal stress distribution of the femoral head changed with the degree of osteoporosis.Changes in the biomechanical environment of the proximal femur have an important impact on osteonecrosis of the femoral head.

Objective To analyze the spatiotemporal distribution characteristics of the syphilis epidemic in Gansu Province from 2005 to 2021, and to provide a reference for the prevention and control of the syphilis epidemic in Gansu Province. Methods ArcGIS 10.7 was used to map the annual incidence of syphilis in Gansu Province from 2005 to 2021, spatial autocorrelation analysis and local autocorrelation analysis were performed, and SaTScan 10.0.2 software was used for spatiotemporal scanning analysis. Results The global autocorrelation results showed that the annual incidence of syphilis in 2005-2021 was >0, Z＞1.96, and the P< 0.0001, showing a spatial clustering distribution, and the local autocorrelation results showed that there was one spatially similar high-high aggregation area and two spatially similar low-low aggregation areas in Gansu Province, and the hot spot analysis showed that there were 9 negative hotspot areas and 2 positive hotspot areas in the syphilis epidemic in Gansu Province. Spatiotemporal scanning analysis detected two high concentration areas, mainly concentrated in Gannan Tibetan Autonomous Prefecture. Conclusion Syphilis in Gansu Province has regional differences in space, and high-high accumulation areas in Gannan Tibetan Autonomous Prefecture persist, and targeted prevention and control strategies should be specified according to temporal and spatial characteristics.

Background Atmospheric fine particulate matter (PM_2.5) can disrupt the metabolic homeostasis of the liver and accelerate the progression of liver diseases, but there are few studies on the effects of sub-chronic PM_2.5 exposure on the liver metabolome. Objectives To investigate the effects of sub-chronic exposure to concentrated PM_2.5 on hepatic metabolomics in mice by liquid chromatography-mass spectrometry (LC-MS), and to identify potentially affected metabolites and metabolic pathways. Methods Twelve male C57BL/6J (6 weeks old) mice were randomly divided into two groups: a concentrated PM_2.5 exposure group and a clean air exposure group. The mice were exposed to concentrated PM_2.5 using the "Shanghai Meteorological and Environmental Animal Exposure System" at Fudan University. The exposure duration was 8 h per day, 6 d per week, for a total of 8 weeks. The mice's liver tissues were collected 24 h after the completion of exposure. LC-MS was performed to assess changes in the hepatic metabolome. Orthogonal partial least squares discriminant analysis and t-test were employed to identify differentially regulated metabolites between the two groups under the conditions of variable important in projection (VIP)≥1.0 and P<0.05. Metabolic pathway enrichment analysis was performed using MetaboAnalyst 5.0 software and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results A total of 297 differentially regulated metabolites were identified between the concentrated PM_2.5 exposure group and the clean air group. Among these metabolites, 142 were upregulated and 155 were downregulated. A total of 38 metabolic pathways were altered, with 7 pathways showing significant perturbation (P<0.05). These pathways involved amino acid metabolism, glucose metabolism, nucleotide metabolism, as well as cofactor and vitamin metabolism. The 7 significant metabolic pathways were pantothenic acid and coenzyme A biosynthesis; purine metabolism; amino sugar and nucleotide sugar metabolism; arginine biosynthesis; alanine, aspartate and glutamate metabolism; aminoacyl-tRNA biosynthesis; and fructose and mannose metabolism. Conclusion The results from metabolomics analysis suggest that sub-chronic exposure to PM_2.5 may disrupt hepatic energy metabolism and induce oxidative stress damage. Aspartic acid, succinic acid, ornithine, fumaric acid, as well as purine and xanthine derivatives, were identified as potential early biomarkers of hepatic response to sub-chronic PM_2.5 exposure.

Objective:To construct a leadership evaluation indicator system for managers in primary healthcare institutions.Methods:This study was a qualitative research. Based on the Chinese Academy of Sciences′ Five Forces Model of Leadership, the framework of the leadership evaluation indicator system for primary healthcare institution managers was initially constructed through literature review, expert interviews, surveys, and group discussions. From November 2020 to June 2021, 19 experts were invited to participate in two rounds of Delphi expert consultations. Based on the consultation results, the leadership evaluation indicator system for primary healthcare institution managers was developed, and the analytic hierarchy process (AHP) was used to determine the weight of each indicator.Results:Nineteen consulting experts were included in the study, 13 of whom were aged 40 years or older, and seven of whom had 20 years or more of professional experience. The response rates of the two rounds of Delphi expert consultation questionnaires were 18/19 and 19/19, respectively; the authority coefficients of the experts were 0.92 and 0.91, respectively. In the second round of consultation, the coordination coefficients of each level of indicators were 0.640, 0.557, and 0.512 ( P<0.05), respectively. The constructed leadership indicator system for managers of primary healthcare institutions included five primary indicators, 16 secondary indicators, and 44 tertiary indicators. The primary indicators, in order of their weight, were "influence"(0.299),"decisiveness"(0.245),"control"(0.156),"inspiration"(0.150), and "foresight"(0.150). Conclusions:This study is a preliminary construction of a leadership evaluation indicator system for managers of primary healthcare institutions, which can be a reference for the training and evaluation of relevant talents.