Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7％of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.

Objective:To observe the effects of 12.5% carbohydrate (CHO) solution and medium chain triglycerides (MCT) solutions at various concentrations on gastric emptying, in order to determine the optimal MCT-CHO combination for enhanced recovery after surgery.Methods:This study was a prospective study. Ten healthy volunteers were selected to ingest 400 ml of the following 5 solutions every day: water, 12.5% CHO, 1% MCT, 2% MCT and 4% MCT. According to the above results, the optimal concentration of MCT solution was 2% MCT, showing comparable gastric emptying rate compared with 12.5% CHO solution. On this basis, combinations of MCT and CHO solutions were determined to be 30 energy % (EN%) MCT+70 EN% CHO and 20 EN% MCT+80 EN% CHO according to the energy distribution ratio. Then the volunteers were given 400 ml of the following 4 solutions every day: 12.5% CHO, 2% MCT, 30 EN% MCT+70 EN% CHO (equivalent to 2% MCT+8% CHO), and 20 EN% MCT+80 EN% CHO (equivalent to 4.4% MCT+10% CHO). Gastric emptying during fasting (T m) and immediately (T 1), 30 min (T 2), 60 min (T 3), 90 min (T 4) and 120 min after ingestion (T 5) were observed by antral ultrasonography. The degree of thirst, hunger, and anxiety was assessed by Visual Analogue Scale, and the taste was rated. Results:The gastric emptying rate in descending order was 20%EN MCT+80%EN CHO group>30%EN MCT+70%EN CHO group≈2％MCT group≈12.5%CHO group. There was no significant difference in gastric emptying rate between 30 EN% MCT+70 EN% CHO group and 12.5% CHO group ( P>0.05). The scores of thirst, hunger and anxiety in 30 EN% MCT+70 EN% CHO group at T 1 to T 5 were significantly lower than those at T m ( P<0.05). 30 EN% MCT+70 EN% CHO group showed the highest taste score. Conclusion:30 EN% MCT+70 EN% CHO solution has similar gastric emptying rate compared with 12.5% CHO solution. It can relieve thirst, hunger, anxiety and other subjective feelings caused by fasting, with tastes better than 12.5% CHO solution.

Objective:To observe the effects of 12.5% carbohydrate (CHO) solution and medium chain triglycerides (MCT) solutions at various concentrations on gastric emptying, in order to determine the optimal MCT-CHO combination for enhanced recovery after surgery.Methods:This study was a prospective study. Ten healthy volunteers were selected to ingest 400 ml of the following 5 solutions every day: water, 12.5% CHO, 1% MCT, 2% MCT and 4% MCT. According to the above results, the optimal concentration of MCT solution was 2% MCT, showing comparable gastric emptying rate compared with 12.5% CHO solution. On this basis, combinations of MCT and CHO solutions were determined to be 30 energy % (EN%) MCT+70 EN% CHO and 20 EN% MCT+80 EN% CHO according to the energy distribution ratio. Then the volunteers were given 400 ml of the following 4 solutions every day: 12.5% CHO, 2% MCT, 30 EN% MCT+70 EN% CHO (equivalent to 2% MCT+8% CHO), and 20 EN% MCT+80 EN% CHO (equivalent to 4.4% MCT+10% CHO). Gastric emptying during fasting (T m) and immediately (T 1), 30 min (T 2), 60 min (T 3), 90 min (T 4) and 120 min after ingestion (T 5) were observed by antral ultrasonography. The degree of thirst, hunger, and anxiety was assessed by Visual Analogue Scale, and the taste was rated. Results:The gastric emptying rate in descending order was 20%EN MCT+80%EN CHO group>30%EN MCT+70%EN CHO group≈2％MCT group≈12.5%CHO group. There was no significant difference in gastric emptying rate between 30 EN% MCT+70 EN% CHO group and 12.5% CHO group ( P>0.05). The scores of thirst, hunger and anxiety in 30 EN% MCT+70 EN% CHO group at T 1 to T 5 were significantly lower than those at T m ( P<0.05). 30 EN% MCT+70 EN% CHO group showed the highest taste score. Conclusion:30 EN% MCT+70 EN% CHO solution has similar gastric emptying rate compared with 12.5% CHO solution. It can relieve thirst, hunger, anxiety and other subjective feelings caused by fasting, with tastes better than 12.5% CHO solution.

Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7％of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.

Objective:To explore the efficacy and adverse reactions of nimotuzumab combined with induction chemotherapy (IC) based on albumin-bound paclitaxel plus cisplatin (TP regimen) for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC).Methods:Clinical data were collected from 65 patients with LA-HNSCC (stages Ⅲ/Ⅳ A/Ⅳ B; excluding nasopharyngeal carcinoma) who received 2-3 cycles of IC followed by concurrent chemoradiotherapy (CRT) in the Second Hospital of Dalian Medical University from January 2018 to June 2022. Based on the IC regimen, these patients were categorized into a nimotuzumab combined with TP (Nimo-TP) group ( n = 34) and a TP group ( n = 31), and their short-term efficacy [i.e., the objective response rate (ORR)], survival outcomes [e.g., overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS)], and adverse reactions were compared. Additionally, factors affecting their survival outcomes were analyzed. Results:There were statistically significant differences in 1- and 2-year DMFS between both groups (90.4% vs. 69.5%, 90.4% vs. 66.0%, χ2=1.81, P < 0.05), so did the ORRs after IC and CRT of both groups (after IC: 67.6% vs. 41.9%, χ2=4.34, P = 0.037; after CRT: 88.2% vs. 67.7%, χ2=4.03, P = 0.045). However, there was no statistically significant difference in the 2-year OS, PFS, and LRFS between both groups ( P > 0.05). Multivariate analysis revealed that nimotuzumab combined with TP-based IC served as an independent prognostic factor for DMFS ( HR = 0.27, 95% CI: 0.07-0.97, P = 0.045), while complete/partial response after IC acted as an independent prognostic factor for both PFS and local relapse-free survival ( HR = 0.36, 95% CI: 0.17-0.76, P = 0.008; HR = 0.28, 95% CI: 0.11-0.69, P = 0.006). Notably, adding nimotuzumab did not aggravate the adverse reactions in the patients during IC and CRT( P > 0.05). Conclusions:Nimotuzumab combined with TP-based induction chemotherapy followed by CRT significantly improved the DMFS of LA-HNSCC patients, exhibiting high safety. However, such therapy failed to significantly improve their OS, PFS, and LRRFS, and, thus, further research is required.

Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8+GZMB+T cells and the decrease of CD8+PD-1+T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.

Objective:To analyze the risk factors for central venous catheter-associated bloodstream infection in patients with emergency hemorrhagic shock.Methods:Patients with hemorrhagic shock and central venous catheterization admitted to the emergency department of Shanghai First People's Hospital from June 2016 to June 2022 were retrospectively analyzed. The patients were divided into infected group and non-infected group according to whether catheter-related bloodstream infection occurred. The puncture site samples and catheter tip samples of infected patients were collected for etiological detection and drug sensitivity test. The difference of baseline data between the two groups was analyzed, and the relationship between central venous catheter-associated infection and influencing factors was analyzed by multivariate logistic regression.Results:A total of 249 patients were included in this study, including 54 patients in the infected group and 195 patients in the non-infected group. There were significant differences in age, catheterization position, ultrasound-guided puncture, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, catheter retention time and application of broad-spectrum antibiotics between the infected group and the non-infected group (all P<0.05). Multivariate logistic regression analysis showed that advanced age, femoral vein catheterization, no ultrasound-guided puncture, high APACHEⅡ score, long catheter indent time and application of broad-spectrum antibiotics were risk factors for central venous catheter-associated bloodstream infection. Among the 54 infected patients, Staphylococcus epidermidis accounted for 44.4%, followed by Escherichia coli accounted for 24.1% and fungus accounted for 11.1%. The resistance rate of gram-positive cocci to vancomycin was the lowest (3.4%) followed by tetracycline (34.5%), and the highest resistance rate was amoxicillin (100.0%). The resistance rates of gram-negative bacilli to amikacin and ceftriaxone were relatively high, both of which were 94.7%. Conclusions:The risk factors for central venous catheter-related blood stream infection in patients with emergency hemorrhagic shock included advanced age, femoral vein catheterization, no ultrasound-guided puncture, high APACHEⅡ score, long catheter retention time and use of broad-spectrum antibiotics. The common pathogenic bacteria were Staphylococcus epidermidis and Escherichia coli.

【Objective】 To investigate and analyze the serological and molecular biological characteristics of B(A) subgroup in a tertiary hospital in Jiaozhou, Qingdao. 【Methods】 From November 2019 to February 2023, the samples of 12 patients were suspected to be AB subgroup by microcolumn glass bead method and saline test tube method. The exons 6 and 7 of ABO gene were further amplified, sequenced and analyzed to determine the ABO allele type. 【Results】 A total of 9 cases of B(A) subgroup were detected in 26 065 patients in Jiaozhou, with a detection rate of 0.345 ‰ ( 9/26 065 ). Among the 9 cases of B(A) subgroup, 8 cases of serological reaction showed AweakB, and the gene detection was heterozygous for BA.04 gene and O gene.One case of serological reaction showed ABweak, and the gene detection was heterozygous for BA.04 gene and A gene. 【Conclusion】 Blood group serological combined with gene detection can accurately identify ABO blood group. B(A) subgroup alleles can exist in individuals with serological reaction of ABweak.

Objective:To evaluate the clinical efficacy of continuous renal replacement therapy (CRRT) with adsorptive filter oXiris in the treatment of severe acute pancreatitis (SAP).Methods:The clinical data of 5 SAP patients who received the treatment of absorptive filter oXiris in Department of Critical Care Medicine of Shanghai General Hospital from February 2021 to February 2022 were collected. The changes of inflammatory indicators, hemodynamics, acid-base balance indicators and organ function indicators were compared before and 24 h after treatment.Results:Before the treatment of oXiris, 3 patients had pancreatic necrotic infection, and all the five patients had systemic inflammatory response syndrome(SIRS), acute respiratory and circulatory failure and acute renal injury. At 24 h after the treatment with oXiris, the levels of inflammatory indicators such as white blood cell count [(13.4±5.0)×10 9/L vs (25.8±10.0)×10 9/L), CRP [(149.6±68.3)mg/L] vs (289.0±129.4)mg/L] and procalcitonin [3.7(1.4, 17.7)ng/ml vs 12.2(3.2, 62.9)ng/ml] in the blood samples from the patients were greatly decreased. Hemodynamics were obviously improved; heart rate [(107.4±9.5)bpm/min vs (143.4±9.7)bpm/min] was decreased, and the mean artery pressure [(87±5)mmHg vs (73±13)mmHg], 1 mmHg=0.133 kPa] tended to be stabilized. Metabolic acidosis was significantly improved; pH value (7.4±0.0 vs 7.2±0.1) and base excess (-2.1±2.5 vs -14.5±6.1) were increased, while lactic acid [(2.6±1.2)mmol/L vs (10.62±6.55)mmol/L] was decreased. Organ dysfunctions were improved; PaO 2/FiO 2 value (241.7±58.5 vs 115.9±53.6) was increased, while serum creatinine [(148.0±42.5)μmol/L vs (232.8±77.4)μmol/L], intra-abdominal pressure [(18.6±4.5)mmHg vs (24.2±4.0)]mmHg, modified Marshall score [3(3.0, 4.0) vs 6(5.5, 9.0)] and APACHEⅡ score (17.6±2.9 vs 26.0±5.2) were decreased. All the differences above were statistically significant (all P value <0.05). Conclusions:It is safe and feasible to treat SAP patients with CRRT by using oXiris in clinical practice, which may have the functions of clearing inflammatory mediators, stabilizing hemodynamics and acid-base balance and improving organ function.

Background: Autoimmune gastritis (AIG) can lead to hypergastrinemia and enterochromaffin ⁃ like cell hyperplasia, thereby increasing the risk of gastric neuroendocrine neoplasms and gastric adenocarcinoma. However, research on the association between AIG and gastric polyps is limited. Aims: To investigate the risk factors for the development of gastric polyps in AIG patients. Methods: The clinical data of 103 AIG patients visited the Chinese People’s Armed Police Force Sichuan Provincial Corps Hospital from June 2019 to June 2023 was collected retrospectively. The parameters analyzed included gender, age, anti⁃parietal cell antibody, anti⁃intrinsic factor antibody, pepsinogen (PG)I, PGII, ratio for PGI/ II, gastrin ⁃ 17 (G ⁃ 17), OLGA and OLGIM staging, size, location and pathological types of gastric polyps, vitamin B12, Helicobacter pylori infection and presence of anemia at the year AIG diagnosed. Univariate and multivariate Logistic regression analyses were performed to identify the risk factors for gastric polyps in AIG patients. The predictive performance of the variables was assessed by ROC curve analysis. Results: Among the 103 AIG patients enrolled in the study, 67 (65.05%) were females, and the median age was 58 years old. Fourteen (13.59%) patients had gastric polyps. Compared to patients without gastric polyps, those with gastric polyps had significantly higher levels of serum G ⁃ 17 (P< 0.000 1). Multivariate Logistic regression analysis indicated that G⁃ 17 was an independent risk factor for gastric polyps in AIG patients (OR=1.047, 95% CI: 1.017 ⁃ 1.078, P=0.002). The area under the curve (AUC) of G ⁃ 17 and the Logistic regression model in predicting the gastric polyp formation in AIG patients was 0.811 and 0.884, respectively. The optimal cutoff value of G⁃17 was 69.50 pmol/L, with the sensitivity and specificity of 92.9% and 67.4%, respectively. Conclusions: Serum G⁃17 is a potential prognostic factor for AIG. The optimal cutoff value for predicting the development of gastric polyp is 69.50 pmol/L.