OBJECTIVE To explore the clinical characteristics and risk factors for refractory drug-resistant Pseudo-monas aeruginosa infection and evaluate the prognosis so as to provide theoretical bases for effective prevention and control of the refractory drug-resistant P.aeruginosa infection.METHODS A total of 95 patients who were di-agnosed with refractory drug-resistant P.aeruginosa infection and were treated in People's Hospital of Guangdong Province from Jan.2019 to Dec.2023 were assigned as the infection group.Meanwhile,95 patients who did not have drug-resistant P.aeruginosa infection,matched by the age and hospitalization period,were chosen as the non-infection group in a case-control(1∶1 ratio).The basic information and clinical data were collected from the two groups of patients.The characteristics and risk factors for the drug-resistant P.aeruginosa infection were ana-lyzed,and the prognosis of the patients was evaluated.RESULTS Among the clinical isolates of drug-resistant P.aeruginosa,78 were isolated from respiratory secretions;there were 59 patients from intensive care unit(ICU),13 patients from respiratory medicine department and 8 patients from geriatrics department.Fever,dyspnea,moist rales and cough were the major clinical manifestations.The proportions of patients with history of respirato-ry tract disease(P＜0.001),renal disease(P=0.008),nervous system disease(P=0.005),diabetes mellitus(P=0.017),hepatic disease(P=0.007),previous utilization rate of aminoglycosides(P=0.002)and previous u-tilization rate of no less than 3 types of antibiotics were higher in the infection group than in the non-infection group.Multivariate analysis showed that the history of respiratory tract disease(OR=2.813,95％CI:1.366 to 5.792,P=0.005),history of diabetes mellitus(OR=2.465,95％CI:1.129 to 5.382,P=0.024)and history of nervous system disease(OR=2.386,95％CI:1.151 to 4.944,P=0.019)were the risk factors for the drug-resist-ant P.aeruginosa infection.The mortality rate of the infection group was 30.53％,higher than 6.32％of the non-infection group(x2=18.527,P＜0.001).CONCLUSIONS The mortality rate of the patients with drug-resistant P.aeruginosa infection is high.The history of respiratory tract disease,history of diabetes mellitus and history of nervous system disease are the major risk factors for the infection.It is necessary for the hospital to strengthen the awareness of prevention of the drug-resistant P.aeruginosa infection so as to curb the hospital-associated infection.

OBJECTIVE To explore the clinical characteristics and risk factors for refractory drug-resistant Pseudo-monas aeruginosa infection and evaluate the prognosis so as to provide theoretical bases for effective prevention and control of the refractory drug-resistant P.aeruginosa infection.METHODS A total of 95 patients who were di-agnosed with refractory drug-resistant P.aeruginosa infection and were treated in People's Hospital of Guangdong Province from Jan.2019 to Dec.2023 were assigned as the infection group.Meanwhile,95 patients who did not have drug-resistant P.aeruginosa infection,matched by the age and hospitalization period,were chosen as the non-infection group in a case-control(1∶1 ratio).The basic information and clinical data were collected from the two groups of patients.The characteristics and risk factors for the drug-resistant P.aeruginosa infection were ana-lyzed,and the prognosis of the patients was evaluated.RESULTS Among the clinical isolates of drug-resistant P.aeruginosa,78 were isolated from respiratory secretions;there were 59 patients from intensive care unit(ICU),13 patients from respiratory medicine department and 8 patients from geriatrics department.Fever,dyspnea,moist rales and cough were the major clinical manifestations.The proportions of patients with history of respirato-ry tract disease(P＜0.001),renal disease(P=0.008),nervous system disease(P=0.005),diabetes mellitus(P=0.017),hepatic disease(P=0.007),previous utilization rate of aminoglycosides(P=0.002)and previous u-tilization rate of no less than 3 types of antibiotics were higher in the infection group than in the non-infection group.Multivariate analysis showed that the history of respiratory tract disease(OR=2.813,95％CI:1.366 to 5.792,P=0.005),history of diabetes mellitus(OR=2.465,95％CI:1.129 to 5.382,P=0.024)and history of nervous system disease(OR=2.386,95％CI:1.151 to 4.944,P=0.019)were the risk factors for the drug-resist-ant P.aeruginosa infection.The mortality rate of the infection group was 30.53％,higher than 6.32％of the non-infection group(x2=18.527,P＜0.001).CONCLUSIONS The mortality rate of the patients with drug-resistant P.aeruginosa infection is high.The history of respiratory tract disease,history of diabetes mellitus and history of nervous system disease are the major risk factors for the infection.It is necessary for the hospital to strengthen the awareness of prevention of the drug-resistant P.aeruginosa infection so as to curb the hospital-associated infection.

Bruton's tyrosine kinase inhibitors (BTKi) are a class of novel small-molecule targeted antitumor drugs used to treat B-cell malignancies. However, safety issues associated with BTKi may lead to treatment interruption, compromising their efficacy. To promote the standardized management of safety in BTKi treatment, Evidence-Based Pharmacy Professional Committee of the Chinese Pharmaceutical Association, Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association, Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society, Expert Committee on Lymphoma of Chinese Society of Clinical Oncology, Expert Committee on Leukemia of Chinese Society of Clinical Oncology, Integrated Cancer Cardiology Branch of China Anti-Cancer Association, Hematology Branch of the Chinese Medical Association, and Hospital Pharmacy Professional Committee of the Cross-Straits Medicine Exchange Association formulated the Evidence-based Expert Consensus on the Clinical Management of Safety of Bruton′s Tyrosine Kinase Inhibitors (2024), which was published in the Chinese Journal of Cancer Research in June 2024. It covered 9 clinical issues in the following 3 domains: (1) the management of common adverse reactions of BTKi such as bleeding, cardiovascular events, hematological toxicity, infections, rashes, diarrhea, and arthralgia; (2) the management of drug-drug interactions; (3) management guidance for special populations. This consensus provides evidence-based recommendations for the safety management of BTKi medication in clinical practice. This article provides an interpretation and evidence summary of the consensus in Chinese, aiming to facilitate its implementation in China, enhance the safety management of BTKi treatment, and improve patient outcomes.

Copper is an indispensable trace element that participates in numerous metabolic and signaling processes in both its oxidized and reduced states.It is intimately associated with several facets of tumor development,and alterations in copper homeostasis can substantially influence processes such as tumor cell growth,metastasis,modulation of the tumor microenvironment,oxidative stress,cell signaling,and the evasion of tumor cells from immune surveillance.Copper metabolism in tumor cells predominantly promotes immune escape by regulating the expression of programmed death ligand 1.In view of its crucial role in tumor immunity,modulating copper metabolism has emerged as a prospective therapeutic approach.This paper reviews the regulatory mechanisms of copper within the human body and investigates how disruptions to copper metabolism impact tumorigenesis and progression,along with the immune and tumor microenvironments.We also discuss the research value of copper as a target for tumor immunotherapy,thus providing a theoretical basis for future research and clinical applications.

Copper is an indispensable trace element that participates in numerous metabolic and signaling processes in both its oxidized and reduced states.It is intimately associated with several facets of tumor development,and alterations in copper homeostasis can substantially influence processes such as tumor cell growth,metastasis,modulation of the tumor microenvironment,oxidative stress,cell signaling,and the evasion of tumor cells from immune surveillance.Copper metabolism in tumor cells predominantly promotes immune escape by regulating the expression of programmed death ligand 1.In view of its crucial role in tumor immunity,modulating copper metabolism has emerged as a prospective therapeutic approach.This paper reviews the regulatory mechanisms of copper within the human body and investigates how disruptions to copper metabolism impact tumorigenesis and progression,along with the immune and tumor microenvironments.We also discuss the research value of copper as a target for tumor immunotherapy,thus providing a theoretical basis for future research and clinical applications.

Bruton's tyrosine kinase inhibitors (BTKi) are a class of novel small-molecule targeted antitumor drugs used to treat B-cell malignancies. However, safety issues associated with BTKi may lead to treatment interruption, compromising their efficacy. To promote the standardized management of safety in BTKi treatment, Evidence-Based Pharmacy Professional Committee of the Chinese Pharmaceutical Association, Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association, Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society, Expert Committee on Lymphoma of Chinese Society of Clinical Oncology, Expert Committee on Leukemia of Chinese Society of Clinical Oncology, Integrated Cancer Cardiology Branch of China Anti-Cancer Association, Hematology Branch of the Chinese Medical Association, and Hospital Pharmacy Professional Committee of the Cross-Straits Medicine Exchange Association formulated the Evidence-based Expert Consensus on the Clinical Management of Safety of Bruton′s Tyrosine Kinase Inhibitors (2024), which was published in the Chinese Journal of Cancer Research in June 2024. It covered 9 clinical issues in the following 3 domains: (1) the management of common adverse reactions of BTKi such as bleeding, cardiovascular events, hematological toxicity, infections, rashes, diarrhea, and arthralgia; (2) the management of drug-drug interactions; (3) management guidance for special populations. This consensus provides evidence-based recommendations for the safety management of BTKi medication in clinical practice. This article provides an interpretation and evidence summary of the consensus in Chinese, aiming to facilitate its implementation in China, enhance the safety management of BTKi treatment, and improve patient outcomes.

Objective To analyze the situation of perinatal birth defects in 13 monitoring hospitals in Changsha City from 2011 to 2020, and to explore the composition characteristics and changes of birth defects in Changsha. Methods The monitoring data of perinatal birth defects in 13 surveillance hospitals in Changsha City from 2011 to 2020 were collected and statistically analyzed. Results From 2011 to 2020, the total number of perinatal infants in the 13 surveillance institutions in Changsha was 541,234, showing a trend of rising first and then falling. A total of 15 725 cases of birth defects were found, and the incidence rate of birth defects in perinatal period was 290.54/10 000. The incidence of birth defects in 2020 decreased by 41.93% compared with 2011. The incidence of perinatal birth defects in males (326.59/10,000) was higher than that in females (248.96/10 000), and the difference was statistically significant (χ²=288.955, P＜0.05). The incidence of perinatal birth defects in urban areas (312.65/10,000) was higher than that in rural areas (262.26/10 000), and the difference was statistically significant (χ²=119.974, P＜0.05). The incidence of birth defects in perinatal infants born to mothers under 20 years old was higher than that in other age groups. The top five major birth defects were congenital heart disease, polydactyly, external ear malformation, clubfoot, and hypospadias. Conclusion The incidence of perinatal birth defects in Changsha shows an overall downward trend , and the prevention and control measures for birth defects have shown effectiveness. To consolidate the achievements and control the incidence at a low level, the tertiary prevention of birth defects should be further strengthened.

【Objective】 To analyze the effects of different fortified feeding methods on nutritional metabolism and growth rate of preterm very low birth weight infants (VLBWI), in order to provide new clues for improving the prognosis of the preterm infants. 【Methods】 A total of 115 cases of premature VLBWI admitted to Department of Neonatology, The First Affiliated Hospital of Kunming Medical University from January 2019 to December 2020 were included in this study, and were divided into fortified breastfeeding group (HFM group), mixed feeding group, and premature formula feeding group (PF group) based on their feeding methods. The effects of different feeding methods on the nutritional metabolism and growth rate of premature VLBWI were analyzed. 【Results】 1) The hospitalization time of infants in the HFM group was shorter than that in PF group and mixed feeding group (t=7.185, 6.924, P<0.05). 2) The proportion of necrotizing enterocolitis (NEC) in the HFM group during hospitalization was lower than that in the PF group (P<0.05); the proportions of late onset septicemia(LOS) and extra uterine growth restriction(EUGR) in the HFM group during hospitalization were lower than those in the PF group (χ²=5.030, 4.147, P<0.05); the proportion of LOS was lower than that of the mixed feeding group(χ²=6.589, P<0.05). 3) During hospitalization, the proportions of abdominal distension, bloody stools and increased eosinophils in the HFM group were lower than those in the PF group (P<0.05), which in mixed feeding group was lower than those in PF group (Fisher exact test, P<0.05). 4) At discharge, the weight and length growth rate of the HFM group were higher than those of the mixed feeding group (t=3.722, 0.425, P<0.001) and the PF group (t =6.015, 0.496, P< 0.001). 【Conclusion】 Fortified breastfeeding can more effectively increase the growth rate of VLBWI in premature infants, improve nutritional metabolism, reduce complications and adverse feeding reactions related to premature infants, and is safer and more effective.

Objective:The drug-resistant genes carried by carbapenem-resistant Klebsiella pneumoniae(CRKP)limit clinical treatment options,and its virulence genes severely affect patient prognosis.This study aims to investigate the distribution of virulence genes,capsular serotypes,and molecular epidemiological characteristics of CRKP in ICU,to understand the characteristics of CRKP infections in ICU,and to provide a scientific basis for effective monitoring and control of CRKP infections in ICU. Methods:A total of 40 non-duplicate strains of CRKP isolated from the ICU of Guangdong Provincial People's Hospital between January 2021 and December 2022 were collected and analyzed.Whole-genome sequencing was used to analyze the distribution of resistance genes,virulence genes,and capsular serotypes of the strains.The sequences of 7 housekeeping genes of CRKP genome were uploaded to the Klebsiella pneumoniae(KPN)multilocus sequence typing(MLST)database to determine the sequence types(STs)of the strains. Results:The age of the 40 ICU CRKP-infected patients was(69.03±17.82)years old,with various underlying diseases,and there were 20 patients with improved clinical outcome and 20 patients with death.The isolated strains primarily originated from mid-stream urine and bronchoalveolar lavage fluid.Whole-genome sequencing results revealed that the strains predominantly carried blaKPC-1(29 strains,72.5%)and blaNDM-1(6 strains,15.0%),with 5 strains carrying both blaKPC-1 and blaNDM-1.Various virulence genes were detected,among which the carriage rates of genes such as entA,entB,entE,entS,fepA,fepC,fepG,yag/ecp,and ompA reached 100%,while the carriage rates of genes such as entD,fimB,iroB,iroD,fes,and pla were low.The CRKP strains isolated from ICU were predominantly ST11(27 cases,67.5%),with KL64 being the main capsular serotype(29 cases,72.5%).A total of 23 ST11-KL64 CRKP strains were detected,accounting for 57.5%. Conclusion:The main type of ICU CRKP is ST11-KL64,carrying various virulence genes,primarily those related to iron absorption.Furthermore,blaKPC has shifted from blaKPC-2 to blaKPC-1.Therefore,close monitoring of the molecular epidemiological changes of CRKP is necessary,and strict control measures should be implemented to effectively curb the occurrence of CRKP infections.

ObjectiveTo observe the effect of Sanhuang Tangshenkang on the Wnt/β-catenin signaling pathway in the bone tissue of diabetic rats. MethodA high-sugar and high-fat diet was administered for 4 weeks， along with intraperitoneal injection of freshly prepared 2% streptozotocin （pH 4.5） at 30 mg·kg^-1 body weight to induce a diabetes model in rats. The rats with diabetes were randomly divided into model group， low- and high-dose Sanhuang Tangshenkang groups （12.8， 38.4 g·kg^-1）， and Gushukang group （1.8 g·kg^-1） according to the blood glucose level. Rats of the same age were fed on a regular diet and assigned to the control group. After 12 weeks of respective treatments with drugs or physiological saline， the fasting blood glucose （FBG） levels of the rats were measured using an automated biochemical analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to detect fasting serum insulin （FINS）， bone-specific alkaline phosphatase （BALP）， and tartrate-resistant acid phosphatase （TRAP） levels. Micro-computed tomography （Micro-CT） was used to scan the femurs of rats to observe bone tissue microstructure and measure bone mineral density （BMD）. Hematoxylin-eosin （HE） staining and safranin O/fast green staining were performed to observe pathological changes in the femoral bone tissue. Immunohistochemistry （IHC） and Western blot were used to detect the expression of Wnt3a， low-density lipoprotein receptor-related protein 5 （LRP-5）， and β-catenin proteins. ResultCompared with the control group， the model group showed a significant increase in FBG， FINS， and TRAP levels （P<0.01）， a significant decrease in BALP level （P<0.01）， a significant decrease in BMD （P<0.01）， and disorganized， elongated， and sparse bone trabecular structures with fractures and increased lipid droplets. Additionally， the expression of Wnt3a， LRP-5， and β-catenin proteins decreased （P<0.05， P<0.01）. Compared with the model group， the low- and high-dose Sanhuang Tangshenkang groups showed a reduction in FBG and an increase in BALP （P<0.05）. The low-dose Sanhuang Tangshenkang group also exhibited a decrease in FINS （P<0.05）. All treatment groups showed a significant decrease in TRAP （P<0.01）， varying degrees of improvement in BMD （P<0.05， P<0.01））， increased and denser bone trabeculae with more regular arrangements and reduced lipid droplets， and improved bone microstructure morphology. The average optical density values of Wnt3a， LRP-5， and β-catenin proteins were significantly increased in all drug-treated groups （P<0.05， P<0.01）， and the expression of Wnt3a， LRP-5， and β-catenin proteins was elevated （P<0.05， P<0.01）. ConclusionSanhuang Tangshenkang may regulate the imbalance of the Wnt/β-catenin signaling pathway by increasing the expression of Wnt3a， LRP-5， and β-catenin proteins in bone tissue， which may promote bone formation， reduce bone resorption， and lower blood glucose levels， thereby achieving the effect of preventing and treating diabetic osteoporosis.