OBJECTIVE To explore the effects of CD20 coding gene （MS4A1） polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020， with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software， including rs1051461， rs17155034， rs4939364， and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors（demographic， clinical， and genotypic variables） in patients and the steady-state trough concentration of rituximab during the first course of treatment， followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival （PFS） and overall survival （OS）. Using MS4A1 genotype and tumor stage as independent variables， Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL，which was significantly lower than 21.95 μg/mL in AA+AC carriers （P＜0.05）. The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers， CT+TT carriers had significantly prolonged PFS and OS （P＜0.05）. The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype （HR＝4.406， 95%CI：1.743-11.137， P＜0.05） and tumor Ⅲ&Ⅳ （HR＝3.233， 95%CI： 1.413-7.399， P＜0.05） were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab， and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.

Heart failure is the leading cause of mortality in cardiovascular diseases and represents the ultimate common manifestation of most cardiovascular conditions,impacting over 60 million individuals globally.Currently,heart transplantation remains the standard treatment for heart failure patients.Adherence to fundamental pharmacotherapy can improve quality of life and extend survival time for heart failure patients.However,due to the complex mechanism of heart failure and numerous complications,the limitations of conventional heart failure treatment strategies in clinical work are gradually magnified.In recent years,interventional therapy has emerged as an innovative approach for managing heart failure,attracting significant attention and achieving substantial breakthroughs that offer new hope for affected individuals.Injectable hydrogel has garnered considerable interest in biomedicine due to its minimally invasive nature and capacity for efficient therapeutic drug delivery.In the context of chronic heart failure,injectable hydrogel finds application primarily in tissue regeneration,drug delivery,and immunotherapy.This review mainly describes the application and research progress of injectable hydrogel in the treatment of heart failure.

Objective:This study aims to discuss the diagnosis and treatment of pediatric appendicovesical fistula (AVF).Methods:A retrospective analysis was conducted on the clinical data of a pediatric patient with AVF admitted to our hospital in March 2023. The patient was a 6-year and 11-month old male who was hospitalized on March 21, 2023, due to difficulty urinating accompanied by diarrhea for two weeks. Computed tomography (CT) revealed bladder stones. The preoperative diagnosis was bladder stones. Transurethral cystoscopic lithotripsy with laser was performed under general anesthesia. Two weeks postoperatively, the child presented with recurrent symptoms of frequent urination, urinary pain, and diarrhea. Urine routine examination indicated a urinary tract infection. Over a month of antibiotic treatment was ineffective, and symptoms such as pneumaturia and fecaluria emerged, with exacerbation of diarrhea, suggesting the possibility of a fistulous tract between the child's intestine and bladder. Further bladder ultrasonography with contrast showed microbubbles of contrast medium leaking from the right posterior bladder wall into the intestinal tract. Enhanced magnetic resonance imaging (MRI) demonstrated a small, sharp tube-like shadow at the upper edge of the right posterior bladder, with a strip-like, significantly enhanced shadow within the lumen. The preoperative diagnosis was revised to appendicovesical fistula. During cystoscopic examination, a papillary-like protrusion was identified on the right lateral wall of the bladder, with no evident orificium fistulae or foreign body discharge noted at the protrusion site. Consequently, robot-assisted laparoscopic partial cystectomy, appendectomy, and lysis of adhesions were performed.Results:The patient was administered antibiotic for a 10-day course of anti-infection and a urinary catheter was maintained for 13 days. The patient recovered entirely and had been discharged after the removal of the urinary catheter. At an 11-month follow-up, there were no reported specific discomforts.Conclusions:Pediatric AVF is rare, and bladder contrast-enhanced ultrasonography and MRI are preferred for initial diagnostic evaluation. The diagnosis can be confirmed by specific clinical presentations such as intermittent pneumaturia and fecaluria, diarrhea with bladder stones. Laparoscopic surgery or robot-assisted laparoscopic surgery could be a feasible treatment option.

Objective:To investigate the effect of spouse smoking cessation(SSC)on the pregnancy outcome of the patients with polycystic ovary syndrome(PCOS)based on a secondary analysis of the results of a large randomized clinical trial.Methods:Basedon the inclusion and exclusion criteria,this secondary analysis included 861 female participants in the Trial of Acu-puncture Combined with Clomiphene for PCOS from 2011 to 2015.According to the smoking status of their husbands,we divided the subjects into a smoking group(n=345),a non-smoking group(n=387),and a smoking cessation group(n=129),collected their general demographics,anthropometric indexes,laboratory results and pregnancy outcomes,compared them among the three groups,and analyzed the relationship of SSC with the pregnancy outcomes of the PCOS patients.Results:The levels of total testos-terone(T)and low-density lipoprotein cholesterol(LDL-C)in the smoking cessation group were similar to those in the non-smoking group,but significantly lower than those in the smoking group(P=0.014 and P=0.011).The contents of fasting insulin,total cho-lesterol,and apolipoprotein B exhibited statistically significant differences among the three groups(P=0.029,P=0.018 and P=0.024),dramatically lower in the smoking cessation and non-smoking groups than in the smoking group,but similar between the for-mer two.The ovulation rate of the smoking cessation group was similar to that of the non-smoking group,remarkably higher than that of the smoking group(P=0.038).No statistically significant differences were observed in other indicators among the three groups(P＞0.05).Multivariate logistic regression analysis showed that SSC during pregnancy preparation was a protective factor for ovulation in the PCOS patients(OR=1.74,95％CI:1.04-2.92,P=0.035).Conclusion:SSC can improve androgen and glucolipid me-tabolisms of infertile patients with PCOS,and thereby significantly increase the ovulation rate.It is of positive significance to encourage SSC clinically for improving the pregnancy outcomes of infertile women with PCOS.

AIM To study the secondary metabolites from the endophytic fungi Candida sp.of Berberis atrocarpa Schneid.METHODS The ethyl acetate fraction and petroleum ether fraction from the secondary metabolites of Candida sp.fermentation extract were separated and purified by silica gel,Sephadex LH-20 and preparative liquid chromatography,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as 1-phenyl-1,2-ethanediol(1),4-hydroxyphenethyl alcohol(2),4-hydroxybenzoic acid(3),4-hydroxyphenylacetic acid(4),3-hydroxyphenylacetic acid(5),3-methylsulfinyl propionic acid(6),phenylacetic acid(7),(S)-N-nitroso-1-amino-p-hydroxy phenylethanol(8),2-phenylacetamide(9),p-hydroxybenzaldehyde(10),ethyl 2-(4-hydroxyphenyl)acetate(11),dibutyl phthalate(12),5,5'-dimethoxybiphenyl-2,2'-diol(13),3-indolealdehyde(14),N-acetyl-L-phenylalanine(15),9-hydroxy-10E,12Z-octadecadienoic acid(16),9-hydroxy-10E,12E-octadecadienoic acid(17),(6E)-5-methylene-6-tetradecenoic acid(18).CONCLUSION Compounds 1,3-8 and 10-18 are isolated from Candida sp for the first time.

Objective:To investigate the safety, feasibility and accuracy of esophageal sponge cytology in esophageal carcinoma screening in high-incidence districts.Methods:Opportunistic screening for esophageal carcinoma was conducted on individuals aged 40-75 years with high-risk factors for esophageal carcinoma and visited out-patient clinic in Lianshui People's Hospital from May 2021 to June 2022. A new esophageal cell collector independently developed in China was used for esophageal sponge cytology sampling followed by cytopathological analysis. Atypical squamous cells or more severe lesions were defined as positive esophageal sponge cytology. Then gastroscopy was performed, and all suspicious areas under the endoscopy were biopsied for histopathological examination. Gastroscopy, biopsy histopathology and esophageal sponge cytology were conducted blindly in pairs. Outcome measures included adverse reactions during sampling, subject tolerability (using a visual simulation score), sampling quality, and diagnostic efficacy of esophageal sponge cytology using gastroscopy plus biopsy histopathology as the gold standard.Results:A total of 1 590 patients completed the screening program. During esophageal sponge cytology sampling, no serious adverse events were observed, and the adverse reactions were mainly manifested as vomiting during sampling [0.31% (5/1 590)] and sore throat after sampling [2.45% (39/1 590)], all of which resolved spontaneously without further medical intervention. The majority of subjects [98.62% (1 568/1 590)] reported good tolerance during the procedure. After sampling, 1 526 (95.97%) subjects had completely expanded sponge material, meeting the standard of good sampling quality. The scanning analysis of the digital pathology system showed that the number of sampled cells in 1 590 subjects ranged (2.01-4.00)×10 6, with a median of 3.48×10 6 cells, which could meet the requirements for interpreting cytological results. Using the positive esophageal sponge cytology for the diagnosis of esophageal carcinoma including high-grade intraepithelial neoplasia, esophageal squamous cell carcinoma and adenocarcinoma of esophagogastric junction, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 98.57% (69/70), 91.51% (1 391/1 520), 34.85% (69/198), 99.93% (1 391/1 392), and 91.82% (1 460/1 590), respectively. Conclusion:Esophageal sponge cytology presents promising diagnostic efficacy for esophageal carcinoma screening, offering a simple, safe, convenient, and effective approach in high-incidence esophageal carcinoma regions.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To develop effective measures to reduce antibiotic use duration in very low birth weight(VLBW)preterm infants in the neonatal intensive care unit through quality improvement methods.Methods The study population consisted of hospitalized VLBW preterm infants,with the percentage of hospitalization time during which antibiotics were used from November 2020 to June 2021 serving as the baseline.The specific quality improvement goal was to reduce the duration of antibiotic use.Factors affecting antibiotic use duration in preterm infants were analyzed using Pareto charts.Key drivers were identified,and specific interventions were formulated based on the stages of antibiotic use.Changes in the percentage of antibiotic use duration were monitored with run charts until the quality improvement target was achieved.Results From November 2020 to June 2021,the baseline antibiotic use duration percentage was 49%,with a quality improvement target to reduce this by 10%within 12 months.The Pareto analysis indicated that major factors influencing antibiotic duration included non-standard antibiotic use;delayed cessation of antibiotics when no infection evidence was present;prolonged central venous catheter placement;insufficient application of kangaroo care;and delayed progress in enteral nutrition.The interventions implemented included:(1)establishing sepsis evaluation and management standards;(2)educating medical staff on the rational use of antibiotics for preterm infants;(3)supervising the enforcement of antibiotic use standards during ward rounds;(4)for those without clear signs of infection and with negative blood cultures,discontinued the use of antibiotics 36 hours after initiation;(5)reducing the duration of central venous catheterization and parenteral nutrition to lower the risk of infection in preterm infants.The control chart showed that with continuous implementation of interventions,the percentage of antibiotic use duration was reduced from 49%to 32%,a statistically significant decrease.Conclusions The application of quality improvement tools based on statistical principles and process control may significantly reduce the antibiotic use duration in VLBW preterm infants.

Objective To compare the detection rates and antimicrobial resistance rates of Klebsiella pneumoniae(KP)between the intensive care unit of The First People's Hospital of Changzhou(CZFPH-ICU)and the American Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ),as well as the changes in the antimicrobial resistance rate of KP and detection rate of carbapenem-resistant KP(CRKP)in CZFPH-ICU.Methods Differences in speci-men distribution and antimicrobial resistance rate of KP detected from CZFPH-ICU and MIMIC-Ⅳ from 2017 to 2019,as well as the changing trends of specimen distribution,antimicrobial resistance rate,detection rates of KP and CRKP from different specimen sources in CZFPH-ICU from 2017 to 2023 were retrospectively analyzed.Results A total of 2 434 strains of KP were detected in CZFPH-ICU from 2017 to 2019,mainly from sputum specimens.A total of 1 137 strains of KP were detected from MIMIC-Ⅳ database,mainly from urine specimens.Compared with MIMIC-Ⅳ,KP detected from CZFPH-ICU showed higher resistance rate to commonly used antimicrobial agents.A total of 4 874 strains of KP were detected from CZFPH-ICU from 2020 to 2023,mainly from sputum specimens.The detection rates of CRKP from sputum,urine,drainage fluid and bile specimens decreased from 17.77％,20.15％,24.22％and 24.07％in 2017-2019 to 12.99％,13.56％,13.63％and 8.00％in 2020-2023,respectively(all P＜0.05).The changing trend of resistance rate of KP isolated from CZFPH-ICU from 2017 to 2023 to commonly used antimicrobial agents such as piperacillin/tazobactam,imipenem,and meropenem increased in 2017-2019,decreased in 2020-2022,and slightly increased in 2023.In 2013,the resistance rates of KP isolated from CZFPH-ICU to ceftazidime/avibactam,polycolistin B and tigacycline were 21.28％,10.22％and 7.03％,respectively.Conclusion In recent 7 years,resistance rate of KP from CZFPH-ICU showed a slow decline trend,but it was still higher than that in foreign MIMIC-Ⅳ database.Hospitals should strengthen various infection prevention and control measures to ef-fectively control KP resistance and infection.

Precancerous lesions of gastric cancer is a key stage in the development of gastric cancer.The reprogramming of glucose metabolism is a prominent feature of precancerous lesions of gastric cancer.Hypoxic microenvironment and hypoxia-inducible factors are important factors influencing the occurrence of glucose metabolic reprogramming.This article summarized the relationship between hypoxic microenvironment and the reprogramming of glucose metabolism in precancerous lesions of gastric cancer,and concluded the relevant research on TCM compounds and effective components to improve hypoxic microenvironment and further regulate glycolysis for the treatment of this disease.It was concluded that the mechanism may be the inhibition of angiogenesis,regulation of signaling pathways and key proteins of glycolysis,expression of multiple enzymes,reduction of lactate secretion,inhibition of cell malignant proliferation and invasion.It explored the mechanism of Chinese materia medica in improving hypoxic microenvironment and regulating glycolysis,so as to provide reference for the prevention and treatment of precancerous lesions of gastric cancer.