Objective To observe the clinical efficacy and safety of vericiguat tablets combined with sacubitril valsartan sodium(Sac/Val)tablets in the treatment of patients with heart failure with reduced ejection fraction(HFrEF).Methods The HFrEF patients were divided into control group and treatment group according to the cohort method.The control group was treated with Sac/Val tablets 200 mg per time,bid,orally.On the basis of control group,the treatment group was treated with vericiguat tablets 2.5 mg per time,qd,taken with meal.Two groups were treated for 3 months.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic dimension(LVEDD)and end-systolic diameter(LVESD),levels of high sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6),nitric oxide(NO),N-terminal pro-brain natriuretic peptide(NT-proBNP),blood urea nitrogen(BUN)and serum creatinine(SCr),and safety were compared between the two groups.During follow-up,the heart failure rehospitalization rates and major adverse cardiovascular events were compared between the two groups.Results Treatment group was enrolled 53 patients,control group was enrolled 53 patients.After treatment,the total effective rates of treatment and control groups were 94.34％(50 cases/53 cases)and 81.13％(43 cases/53 cases)with statistical significant difference(P＜0.05).After treatment,the LVEF of treatment and control groups were(48.02±5.20)％and(43.02±4.33)％,the LVEDDs were(52.85±6.30)and(55.63±6.88)mm,the LVESDs were(41.64±6.40)and(44.22±5.85)mm,the levels of hs-CRP were(10.22±2.63)and(14.60±2.98)mg L-1,the levels of IL-6 were(14.48±2.40)and(17.36±2.52)pg·mL-1,the levels of NO were(102.60±20.16)and(92.16±16.33)μmol·L-1,the levels of NT-proBNP were(898.74±102.20)and(1315.60±182.64)ng·L-1,the levels of BUN were(12.02±2.28)and(13.45±2.33)mmol·L-1,the levels of SCr were(82.22±5.89)and(85.64±6.03)μmol·L-1,the heart failure rehospitalization rates were 5.66％and 13.21％,respectively;the differences were statistical significant between two groups(all P＜0.05).The adverse drug reactions of treatment group were hyperkalemia,hypotension,renal dysfunction,dizziness and headache,while those in control group were renal dysfunction,hyperkalemia,and hypotension.The major adverse cardiovascular events of treatment group were angina pectoris and acute myocardial infarction,while those in control group were angina pectoris,acute myocardial infarction and atrial fibrillation.The incidences of total adverse drug reactions in treatment and control groups were 13.21％and 7.55％,the incidences of major adverse cardiovascular events were 5.66％and 13.21％,respectively,without statistically significant differences(all P＞0.05).Conclusion Vericiguat tablets combined with Sac/Val tablets have a definitive clinical efficacy in the treatment of HFrEF patients,which can improve cardiac and endothelial function,reduce inflammatory response and readmission times,without increasing the incidences of adverse drug reactions.

Although teniposide(VM26)is widely used in the treatment of lymphoma,its poor water sol-ubility,low bioavailability and systemic toxicities still limit its clinical application.Nano-delivery systems are effective in increasing the bioavailability and reducing the toxicity of VM26,but there is an urgent need to overcome the problem of its non-specific targeting.Therefore,in this paper,we designed and constructed a hyaluronic acid-modified teniposide-targeted nano-delivery system(VM26-TNDS),and characterised its drug encapsulation rate,particle size and zeta potential.We also investigated the effects of VM26-TNDS on B-cell lymphoma cells with different expression of CD44 receptor,in terms of cellular targeting,inhibitory effect of proliferation,and induction of apoptosis and necrosis.The results showed that the drug encapsulation efficiency of VM26-TNDS exceeded 85％,and its liquid formulation could be stably stored at 4 ℃ for more than 6 months without precipitation.Based on CD44 receptor expression,Granta-519(high expression),Raji(medium-low expression)and SU-DHL-4(almost no expression)were screened for cellular experiments.Compared with VM26-NDS,the targeted modification could effec-tively reduce the uptake of VM26-TNDS by RAW264.7 and increase the uptake of VM26-TNDS by CD44 receptor-expressing lymphoma cells.The inhibitory proliferative effect and apoptotic necrosis-inducing a-bility of VM26-TNDS were stronger than those of VM26-NDS for Granta-519 and Raji cells,whereas there was no significant difference in the inhibitory effect on proliferation and ability to induce apoptosis and necrosis between VM26-NDS and VM26-TNDS in SU-DHL-4 cells,reflecting the targeting advantage for VM26-TNDS,as expected.However,its toxic effect on B-cell lymphoma cells only reflected the targeting advantage at some concentrations(0.25 μmol/L and 0.5 μmol/L),which met the expectation.The a-bove results indicate that a teniposide-targeted nano-delivery system,VM26-TNDS,has been successfully prepared in this study.VM26-TNDS improves the delivery efficiency of VM26 by targeting human B-cell lymphoma cells expressing the CD44 receptor,thus killing human B-cell lymphoma cells more effectively and overcoming the problem of non-specific targeting in drug delivery to improve the therapeutic effect.Its biological therapeutic effects and mechanisms still need to be proved by more in vitro and in vivo ex-perimental evidence.

Objective To observe the clinical efficacy and safety of vericiguat tablets combined with sacubitril valsartan sodium(Sac/Val)tablets in the treatment of patients with heart failure with reduced ejection fraction(HFrEF).Methods The HFrEF patients were divided into control group and treatment group according to the cohort method.The control group was treated with Sac/Val tablets 200 mg per time,bid,orally.On the basis of control group,the treatment group was treated with vericiguat tablets 2.5 mg per time,qd,taken with meal.Two groups were treated for 3 months.The clinical efficacy,left ventricular ejection fraction(LVEF),left ventricular end-diastolic dimension(LVEDD)and end-systolic diameter(LVESD),levels of high sensitivity C-reactive protein(hs-CRP),interleukin-6(IL-6),nitric oxide(NO),N-terminal pro-brain natriuretic peptide(NT-proBNP),blood urea nitrogen(BUN)and serum creatinine(SCr),and safety were compared between the two groups.During follow-up,the heart failure rehospitalization rates and major adverse cardiovascular events were compared between the two groups.Results Treatment group was enrolled 53 patients,control group was enrolled 53 patients.After treatment,the total effective rates of treatment and control groups were 94.34％(50 cases/53 cases)and 81.13％(43 cases/53 cases)with statistical significant difference(P＜0.05).After treatment,the LVEF of treatment and control groups were(48.02±5.20)％and(43.02±4.33)％,the LVEDDs were(52.85±6.30)and(55.63±6.88)mm,the LVESDs were(41.64±6.40)and(44.22±5.85)mm,the levels of hs-CRP were(10.22±2.63)and(14.60±2.98)mg L-1,the levels of IL-6 were(14.48±2.40)and(17.36±2.52)pg·mL-1,the levels of NO were(102.60±20.16)and(92.16±16.33)μmol·L-1,the levels of NT-proBNP were(898.74±102.20)and(1315.60±182.64)ng·L-1,the levels of BUN were(12.02±2.28)and(13.45±2.33)mmol·L-1,the levels of SCr were(82.22±5.89)and(85.64±6.03)μmol·L-1,the heart failure rehospitalization rates were 5.66％and 13.21％,respectively;the differences were statistical significant between two groups(all P＜0.05).The adverse drug reactions of treatment group were hyperkalemia,hypotension,renal dysfunction,dizziness and headache,while those in control group were renal dysfunction,hyperkalemia,and hypotension.The major adverse cardiovascular events of treatment group were angina pectoris and acute myocardial infarction,while those in control group were angina pectoris,acute myocardial infarction and atrial fibrillation.The incidences of total adverse drug reactions in treatment and control groups were 13.21％and 7.55％,the incidences of major adverse cardiovascular events were 5.66％and 13.21％,respectively,without statistically significant differences(all P＞0.05).Conclusion Vericiguat tablets combined with Sac/Val tablets have a definitive clinical efficacy in the treatment of HFrEF patients,which can improve cardiac and endothelial function,reduce inflammatory response and readmission times,without increasing the incidences of adverse drug reactions.

Although teniposide(VM26)is widely used in the treatment of lymphoma,its poor water sol-ubility,low bioavailability and systemic toxicities still limit its clinical application.Nano-delivery systems are effective in increasing the bioavailability and reducing the toxicity of VM26,but there is an urgent need to overcome the problem of its non-specific targeting.Therefore,in this paper,we designed and constructed a hyaluronic acid-modified teniposide-targeted nano-delivery system(VM26-TNDS),and characterised its drug encapsulation rate,particle size and zeta potential.We also investigated the effects of VM26-TNDS on B-cell lymphoma cells with different expression of CD44 receptor,in terms of cellular targeting,inhibitory effect of proliferation,and induction of apoptosis and necrosis.The results showed that the drug encapsulation efficiency of VM26-TNDS exceeded 85％,and its liquid formulation could be stably stored at 4 ℃ for more than 6 months without precipitation.Based on CD44 receptor expression,Granta-519(high expression),Raji(medium-low expression)and SU-DHL-4(almost no expression)were screened for cellular experiments.Compared with VM26-NDS,the targeted modification could effec-tively reduce the uptake of VM26-TNDS by RAW264.7 and increase the uptake of VM26-TNDS by CD44 receptor-expressing lymphoma cells.The inhibitory proliferative effect and apoptotic necrosis-inducing a-bility of VM26-TNDS were stronger than those of VM26-NDS for Granta-519 and Raji cells,whereas there was no significant difference in the inhibitory effect on proliferation and ability to induce apoptosis and necrosis between VM26-NDS and VM26-TNDS in SU-DHL-4 cells,reflecting the targeting advantage for VM26-TNDS,as expected.However,its toxic effect on B-cell lymphoma cells only reflected the targeting advantage at some concentrations(0.25 μmol/L and 0.5 μmol/L),which met the expectation.The a-bove results indicate that a teniposide-targeted nano-delivery system,VM26-TNDS,has been successfully prepared in this study.VM26-TNDS improves the delivery efficiency of VM26 by targeting human B-cell lymphoma cells expressing the CD44 receptor,thus killing human B-cell lymphoma cells more effectively and overcoming the problem of non-specific targeting in drug delivery to improve the therapeutic effect.Its biological therapeutic effects and mechanisms still need to be proved by more in vitro and in vivo ex-perimental evidence.

Objective To explore the current status of H.pylori infection in the natural population of Sanya City,analyze its influencing factors,and provide a reference basis for the prevention and control of H.pylori infection.Methods A total of 677 residents from four districts of Sanya City were selected by overall stratified random sampling method,and were subjected to urea 14C breath test and questionnaire survey to calculate the positive rate of H.pylori in the natural population and analyze the influencing factors of H.pylori infection.Results A total of 606 residents were included,and the number of H.pylori positive detections was 261,with a positive detection rate of 38.5％.Among them,different ethnicity,marital status,smoking,eating vegetables and fruits,and literacy level were associated with H.pylori infection(P＜0.05);gender,age,BMI,alcohol consumption,drinking water source,betel quid chewing,and the number of cohabitants were not significantly associated with H.pylori infection(P＞0.05).Family infection was an independent risk factor for H.pylori infection in the natural population of Sanya City,and Li ethnicity,frequent consumption of fruits and vegetables,and college and higher education level were independent protective factors for H.pylori infection in the natural population of Sanya City.Conclusion The rate of H.pylori infection in the natural population of Sanya City is lower than the national average.Consuming more fruits and vegetables and improving the awareness of hygiene protection are conducive to the prevention of H.pylori infection;and the promotion of the family and related members with the same examination and treatment is important to avoid aggregation of infection within the family.

Objective To observe whether SaCoVLM laryngeal mask can cause gastroesophageal reflux when the body position changes(lithotomy position and supine position).Methods A total of 70 patients were selected for elective surgery in Shanghai General Hospital from Dec 1st,2021 to Sep 30th,2022.There were 35 patients with ureteroscopy in urology and 35 patients with ankle surgery in trauma orthopedics selected as lithotomy position group and supine position group,respectively.Under SaCoVLM laryngeal mask anesthesia,a dual probe pH electrode was placed in the esophagus to continuously monitor the pH value in the esophagus.The pH values and their changing trends in the lithotomy position and supine position of the esophagus were compared under general anesthesia with SaCoVLM laryngeal mask ventilation,and the possibility of gastroesophageal reflux occurring in both positions was explored.Results The peak airway pressure at each time point(5 min,10 min,15 min,20 min and 30 min)after body position was determined in the two groups,and it in lithotomy position group was significantly higher than that in supine position group,and the difference was statistically significant(P＜0.05).The middle and upper esophageal pH values of the two groups were compared 10 min after laryngeal mask insertion,and it in lithotomy position group(6.045±0.490)was significantly lower than the supine group(6.532±0.366),and the difference was statistically significant(P＜0.05).The middle and upper esophageal pH values of the two groups were compared 10 min and 15 min after laryngeal mask insertion.They in lithotomy position group were significantly lower than those in supine position group,and the differences were statistically significant(10 min:6.045±0.490 vs.6.532±0.366,P=0.031;15 min:5.828±0.487 vs.6.474±0.411,P=0.048).There was no significant difference in the pH of the middle and upper esophagus between the two groups at 1,5,20 and 30 minutes of laryngeal mask insertion.There was no significant difference in the pH value of the esophageal opening between the two groups at each time point after laryngeal mask insertion.Conclusion Under SaCoVLM laryngeal mask ventilation,the risk of gastroesophageal reflux during lithotomy surgery may be higher than during supine surgery.

The incidence of gastric cancer ranks fifth among malignant tumors worldwide, with the fourth highest mortality rate. A noteworthy characteristic of our country is the high prevalence of advanced-stage patients of approximately 40%. Advanced-stage gastric cancer carries an unfavorable prognosis with median survival of around one year. Diagnosis methods for advanced-stage gastric cancer (such as laparoscopic exploration, molecular profiling, and artificial intelligence) are still being continuously improved, while chemotherapy remains the primary treatment. With the rapid development of medical science, the role of surgical intervention in advanced-stage gastric cancer is becoming increasingly prominent. Therefore, as gastric tumor surgeons, we should consider how to use a combination of treatments, including surgery, chemotherapy, targeted therapy, immunotherapy, and interventional therapy, based on different pathological stages and the heterogeneity of tumors. With a multidisciplinary approach involving experts from various fields, we can collectively improve the survival rate and quality of life for advanced-stage patients. This article provides a brief overview of the current advances in the diagnosis and treatment of advanced-stage gastric cancer, and discusses therapeutic decision primarily from the perspective of surgeons.

Objective To investigate the risk factors for pulmonary infection in patients with acute-on-chronic liver failure(ACLF),and to establish a predictive model.Methods A retrospective analysis was performed for 585 ACLF patients who were admitted to Department of Infectious Diseases,The Second Affiliated Hospital of Air Force Medical University,from January 2009 to September 2022,and according to the condition of pulmonary infection after admission,they were divided into infection group with 213 patients and non-infection group with 372 patients.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between groups.The clinical data of these patients were collected.Univariate and multivariate Logistic regression analyses were used to investigate the risk factors for pulmonary infection in ACLF patients and establish a predictive model,and the receiver operating characteristic(ROC)curve was plotted to assess the predictive value of the model.The Hosmer-Lemeshow test was used to evaluate the degree of fitting of the model,and the ROC curve and the area under the ROC curve(AUC)were used to assess the predictive performance of the model.Results Among the 585 patients with ACLF,213 experienced pulmonary infection,with an infection rate of 36.41%.The multivariate logistic analysis showed that upper gastrointestinal bleeding(odds ratio[OR]=2.463,P=0.047),infection at other sites(OR=2.218,P=0.004),femoral vein catheterization(OR=2.520,P＜0.001),and combined use of two or more antibiotics(OR=2.969,P＜0.001)were risk factors for pulmonary infection in ACLF patients.These factors were included in the risk factor predictive model of Logit(P)=-1.869+0.901×upper gastrointestinal bleeding+0.755×infection at other sites+0.924×femoral vein catheterization+1.088×combined use of two or more antibiotics.The ROC curve analysis showed that the model had a good predictive value(Hosmer-Lemeshow χ2=3.839,P=0.698),with an AUC of 0.753(95%confidence interval:0.700-0.772).Conclusion There is a relatively high incidence rate of pulmonary infection in patients with ACLF,and upper gastrointestinal bleeding,spontaneous peritonitis,femoral vein catheterization,and combined use of two or more antibiotics are related risk factors.The model established based on these factors can effectively predict the onset of pulmonary infection in ACLF patients.

The incidence of gastric cancer ranks fifth among malignant tumors worldwide, with the fourth highest mortality rate. A noteworthy characteristic of our country is the high prevalence of advanced-stage patients of approximately 40%. Advanced-stage gastric cancer carries an unfavorable prognosis with median survival of around one year. Diagnosis methods for advanced-stage gastric cancer (such as laparoscopic exploration, molecular profiling, and artificial intelligence) are still being continuously improved, while chemotherapy remains the primary treatment. With the rapid development of medical science, the role of surgical intervention in advanced-stage gastric cancer is becoming increasingly prominent. Therefore, as gastric tumor surgeons, we should consider how to use a combination of treatments, including surgery, chemotherapy, targeted therapy, immunotherapy, and interventional therapy, based on different pathological stages and the heterogeneity of tumors. With a multidisciplinary approach involving experts from various fields, we can collectively improve the survival rate and quality of life for advanced-stage patients. This article provides a brief overview of the current advances in the diagnosis and treatment of advanced-stage gastric cancer, and discusses therapeutic decision primarily from the perspective of surgeons.

Objective:To investigate the clinical and immunological characteristics of anti-synthetase syndrome(ASS)patients overlap with rheumatoid arthritis(RA).Methods:A retrospective analysis was conducted on ASS patients with arthritis who were treated at Peking University People's Hospital.Data collected included demographic information,clinical manifestations,laboratory features,lymphocyte subsets in peripheral blood,and treatments.The patients with ASS were divided into two groups based on the presence or absence of RA for comparative analysis.Results:A total of 104 ASS patients with arthri-tis were included,among whom 23.1％(24/104)were diagnosed with RA.The ASS with RA group had a significantly higher incidence of rapidly progressive interstitial lung disease(RP-ILD)(41.7％vs.17.6％,P=0.032),number of tender joints[10(7,14)vs.4(0,8),P＜0.001],number of swollen joints[4(2,8)vs.2(0,4),P=0.012],and rate of bone erosion(47.8％vs.2.5％,P＜0.001)compared with the non-RA group.Levels of platelets[(289.57±68.74)× 103/μL vs.(247.94±77.04)×103/μL,P=0.022],erythrocyte sedimentation rate(ESR)[43(19,59)mm/h vs.18(10,44)mm/h,P=0.019],and C-reactive protein(CRP)[19.20(4.80,55.36)mg/L vs.5.68(1.10,14.96)mg/L,P=0.006]were found significantly higher in the ASS with RA group than those in non-RA group.Analysis of immune cells in peripheral blood mononuclear cell(PBMC)showed that sig-nificantly decreased proportions of CLA+Treg cells[(11.12±4.10)％vs.(17.22±8.49)％,P=0.003],B cells[8.56％(4.80％,11.90％)vs.14.55％(8.75％,20.29％),P=0.025],and nat-ural killer(NK)cells[7.56％(4.65％,13.20％)vs.13.25％(7.46％,19.25％),P=0.045]in the overlap group compared with non-RA group.Proportion of Na?ve Th cells[(52.66±17.66)％vs.(40.76±14.96)％,P=0.033)]was significantly increased in overlap group compared with non-RA group.Overlap group had lower rate of complete clinical response than non-RA group(16.7％vs.43.8％,P=0.031).Conclusion:Among ASS patients with arthritis,those with RA have more severe lung and joint involvement and a lower treatment response rate,highlighting the need for early recognition and aggressive intervention.