Objective To study the clinical efficacy and safety of disitamab vedotin(RC48)in the third-line and above third-line treatment of advanced gastric cancer.Methods The clinical data of 30 patients with advanced gastric cancer who had previously failed to receive at least two systemic chemotherapy regimens from August 2020 to August 2022 in Nantong Tumor Hospital were retrospectively analyzed.According to different treatment regimens,they were divided into RC48 group(n=15)and control group(chemotherapy/targeted/immune monotherapy)(n=15).The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS)and treatment-related adverse reactions were observed in the two groups.Results The median follow-up time was 7.5 months.The ORR of RC48 group and control group was 20%vs.0%(P=0.224),DCR was 53.3%vs.20%(P=0.128),mPFS was 4 months vs.3 months(P=0.479),mOS was 18 months vs.5 months(P=0.043).In terms of safety,the most common adverse reactions in the RC48 group and the control group were leukopenia and neutropenia.The overall incidence of adverse reactions in the two groups was compa-rable,and there were no fatal adverse events.Conclusion RC48 has a certain effect in the third-line and above third-line treatment of advanced gastric cancer,and patients are well tolerated.

OBJECTIVE To establish two-dimensional liquid chromatography method for the determination of imipenem blood concentration and apply it in clinical practice. METHODS The method for the determination of imipenem blood concentration was established based on automatic two-dimensional liquid chromatography. The targets were extracted by 1-dimensional column Aston SNCB （50 mm ×4.6 mm， 5 μm） and further separated and determined by 2-dimensional column Aston SCB （250 mm×4.6 mm， 5 μm）. The 1-dimensional mobile phase was imipenem-1D mobile phase [acetonitrile-methanol-water （15∶10∶75， V/V/V）] with a flow rate of 1.0 mL/min； 2-dimensional mobile phase was 72%OPI-1 organic mobile phase （chromatographic grade methanol）-20% BPI-1 alkaline mobile phase [water （containing 20.0 mmol/L ammonium phosphate， pH adjusted to 7.2 with triethylamine）]-8%API-1 acidic mobile phase [water （containing 20.0 mmol/L ammonium phosphate， pH adjusted to 3.0 with phosphoric acid）] with a flow rate of 1.0 mL/min； the column temperature was 40 ℃， UV detection wavelength was 310 nm and injection volume was 100 μL. Elution procedure： 1-dimensional column consisted of imipenem-1D mobile phase with eluting for 0-3.40 min； 2-dimensional column consisted of 72% OPI-1 organic mobile phase-20%BPI-1 alkaline mobile phase-8%API-1 acidic mobile phase with eluting for 3.40-11.00 min. RESULTS The linear range of imipenem was 0.171-18.570 μg/mL （R 2＝0.999 9） with the lower limit of quantification for 0.171 μg/mL； the recovery rate ranged from 93.47% to 106.16%（ n＝5） and the RSDs of both intra-day and inter- day precision were below 15% （n＝5）. The minimum concentration of imipenem in 51 patients ranged from 0 to 19.57 μg/mL. CONCLUSIONS The established method is simple and fast with the large scale of sample， and can be used for the imipenem blood concentration monitoring in patients with severe infection.

Objective:To investigate the correlation between fat distribution and the composite indices of femoral neck strength in obese postmenopausal women.Methods:A total of 293 postmenopausal women with non-low body weight were selected, laboratory tests, body composition analyzer test and double-energy X-ray absorptiometry scan were performed. Based on the body mass index(BMI), they were divided into three groups, the normal BMI group(18.5 kg/m 2≤BMI<24.0 kg/m 2, n=91), the overweight group(24.0 kg/m 2≤BMI<28.0 kg/m 2, n=115), and the obese group(BMI≥28.0 kg/m 2, n=87). The measurement results were analyzed. Results:In the obese group, bone mineral density(BMD) of all sites was higher than that in the normal BMI group and overweight group( P<0.005), compression strength index(CSI), bending strength index(BSI), and impact strength index(ISI) were significantly lower than those in the normal BMI group( P<0.001, P=0.008, P=0.001). In the obese group, waist circumference, waist-hip ratio, total fat mass, appendicular fat mass, and trunk fat mass were risk factors for CSI, BSI and ISI independent of age, fasting blood glucose, and BMI( P<0.05). Visceral fat grade and Chinese visceral adiposity fat index were the risk factors for CSI, BSI, and ISI( P<0.05). Conclusion:The composite indices of femoral neck strength decreased in obese postmenopausal women, and both subcutaneous fat and visceral fat were negatively associated with the composite indices of femoral neck strength.

Objective : To investigate the effect of platelet particles on the extent of intestinal inflammation and in⁃ testinal mucosal permeability in mice with dextran sodium sulfate induced colitis. Methods : The experiment was divided into four groups : normal control group ( n = 10 , drinking sterile distilled water + intraperitoneal injection of 0. 9% sodium chloride solution) , PMPs group ( n = 10 , drinking sterile distilled water + intraperitoneal injection of PMPs) , DSS model group ( n = 10 , drinking DSS solution + intraperitoneal injection of 0. 9% sodium chloride solution) , and experimental group ( n = 15 , drinking DSS solution + intraperitoneal injection of PMPs) . Peripheral blood⁃derived PMPs suspension was collected from inflammatory bowel disease ( IBD) patients. A colitis model was constructed in mice by allowing them to freely drink a 5% DSS solution for 1 week , followed by continuous intraperitoneal injection of PMPs for 7 days. Disease activity index (DAI) scores was recorded daily and the severity of intestinal inflammation with histopathological scores (HI) was assessed by HE staining of colon samples at the end of the experiment. Myeloperoxidase (MPO) , neutrophil elastase (NE) , citrullinated histone H3 (citH3) , and free DNA levels were measured in colon homogenate , observe intestinal mucosal structure by transmission electron microscopy , and intestinal permeability was tested using fluorescein isothiocyanate⁃dextran (FITC⁃D) . Results: Compared with the normal control group , the colonic mucosa of mice in the PMPs group showed edema , severe destruction of epithelial structure , extensive aggregation of inflammatory cells , and increased overall HI score (P < 0. 01) ; the levels of inflammatory factors such as IL⁃1β and TNF⁃α in colonic tissue homogenates of mice in the PMPs group increased (P < 0. 05) , and the expression of NETs increased (P < 0. 05) ; the plasma FITC⁃D level of mice in the PMPs group significantly increased (P < 0. 05) , and the permeability of intestinal mucosa increased. Compared with the DSS group , the experimental group mice had higher plasma FITC⁃D levels ( P < 0. 05 ) and more electron microscopic colonic epithelial damage. Conclusion PMPs induces NETs formation in mice , promotes colonic inflammation in mice , increases intestinal mucosal permeability and aggravates intestinal inflammation in mice with DSS colitis.

Objective:To explore the changes of bone turnover markers and geometric parameters of hip bone in overweight postmenopausal women with metabolic syndrome(MS), as well as the influence of MS components. To analyze the association of these factors with the risk of fracture.Methods:A total of 505 overweight postmenopausal female patients who underwent health check-up in Lianhu Community Service Center, Danyang City, Jiangsu Province from January to December 2017 were selected. According to the MS diagnostic criteria of the International Diabetes Federation(2009), the patients were divided into MS group( n=331)and non-MS group( n=174). Blood samples were collected to determine the level of procollagen type 1 N-terminal propeptide(P1NP)and carboxy-terminal cross-linked telopeptide of type 1 collagen(CTX). Bone mineral density and hip bone geometry parameters were tested with dual-energy X-ray absorptiometry and hip structural analysis software. Results:The incidence of osteoporotic fracture and hip fracture in MS group was significantly higher than that in non-MS group(21.1% vs 13.8%, 4.8% vs 1. 1%, P<0.05). However, the bone mineral density of lumbar vertebra 1-4, femoral neck, and total hip in MS group was significantly higher than that in non-MS group, which remained after adjusting for age( P<0.05), but the difference disappeared after further adjustment for body mass index( P>0.05). The P1NP, CTX, femur strength index(FSI), section modulus(SM), and cross-sectional area(CSA)of MS group were significantly lower than those of non-MS group, the buckling ration(BR)was significantly higher than that in non-MS group, and the differences were still statistically significant after adjusting for age and body mass index( P<0.05). There was no significant difference in bone mineral density of lumbar vertebra 1-4, femoral neck, total hip, P1NP, and CTX between fracture group and non-fracture group in patients with MS. But FSI, SM, cross-sectional moment of inertia(CSMI), and CSA were significantly lower, BR was significantly higher( P<0.05) and femur strength decreased in patients with fracture. Regression analysis showed that high BR was an independent risk factor for fracture risk, while high FSI, SM, CSMI, and CSA were protective factors. Multivariate linear regression analysis showed that wasit circumference, diastolic blood pressure, and fasting plasma glucose were the main MS components affecting bone mineral density, bone turnover indexes, and hip bone geometry parameters. Conclusions:Overweight postmenopausal MS patients had decreased bone turnover rate, femoral strength, and relatively poor bone quality. Hip bone geometry parameters can be used as one of the methods to assess fracture risk in MS patients. Waist circumference, diastolic blood pressure, and fasting blood glucose are the important MS components affecting bone mass and bone quality.

Objective:To explore the risk of hip fracture, changes of composite indices of femoral neck strength and its influential factors in non-low-weight postmenopausal women with type 2 diabetes mellitus(T2DM).Methods:A total of 626 non-low-weight postmenopausal women were selected and divided into type 2 diabetes group, pre-diabetic group, and non-diabetic group according to the diagnostic criteria of the American Diabetes Association in 2010. Each participant completed the questionnaire, physical examination, laboratory examination, and Dual-energy X-ray absorptiometry(DXA) examination.Results:Hip fracture rate in T2DM group was significantly higher than that in non-diabetic group(3.4% vs 0.7%, P<0.05), while no significant difference was observed between pre-diabetic group and non-diabetic group(1.1% vs 0.7%, P>0.05). Bone mineral density(BMD) of lumbar spine 1-4, femoral neck, and total hip was comparable between T2DM group and non-diabetic group or pre-diabetic group and non-diabetic group, respectively( P>0.05). The composite indices of femoral neck strength in T2DM group was significantly lower than that in non-diabetic group( P<0.05), but there was no significant difference between pre-diabetic group and non-diabetic group( P>0.05). Regression analysis showed that age and body mass index were the main influential factors of the femoral neck bone mineral density and the composite indices of femoral neck strength( P<0.05). Conclusion:The composite indices of femoral neck strength could be used as one of the markers to evaluate the risk of hip fracture in type 2 diabetic patients.

Background: Autophagy maintains muscle mass and healthy skeletal muscles. Several recent studies have associated sugar-sweetened beverage (SSB) consumption with diseases. We investigated whether muscle dysfunction due to obesity could be restored by SSB restriction (SR) alone or in combination with exercise (EX) training. Methods: Obese mice were subjected to SR combined with treadmill EX. Intraperitoneal glucose tolerance test, grip strength test, hanging time test, and body composition analysis were performed. Triglyceride (TG) and total cholesterol (TC) serum concentrations and TG concentrations in quadriceps muscles were analyzed. Western blot and reverse transcription-quantitative polymerase chain reaction helped analyze autophagy-related protein and mRNA expression, respectively. Results: SR alone had no significant effect on fasting blood glucose levels, glucose tolerance, and muscle function. However, it had effect on serum TC, serum TG, and BCL2 interacting protein 3 expression. SR+EX improved glucose tolerance and muscle function and increased serum TC utilization than SR alone. SR+EX reduced P62 levels, increased glucose transporter type 4 and peroxisome proliferator-activated receptor γ coactivator-1α protein expression, and improved grip strength relative to the high-fat and high-sucrose liquid (HFHS) group, and this was not observed in the HFHS+EX group. Conclusion SR induced mitophagy-related protein expression in quadriceps, without affecting muscle function. And, the combination of SR and EX activated mitophagy-related proteins and improved muscle function.

Background: Autophagy maintains muscle mass and healthy skeletal muscles. Several recent studies have associated sugar-sweetened beverage (SSB) consumption with diseases. We investigated whether muscle dysfunction due to obesity could be restored by SSB restriction (SR) alone or in combination with exercise (EX) training. Methods: Obese mice were subjected to SR combined with treadmill EX. Intraperitoneal glucose tolerance test, grip strength test, hanging time test, and body composition analysis were performed. Triglyceride (TG) and total cholesterol (TC) serum concentrations and TG concentrations in quadriceps muscles were analyzed. Western blot and reverse transcription-quantitative polymerase chain reaction helped analyze autophagy-related protein and mRNA expression, respectively. Results: SR alone had no significant effect on fasting blood glucose levels, glucose tolerance, and muscle function. However, it had effect on serum TC, serum TG, and BCL2 interacting protein 3 expression. SR+EX improved glucose tolerance and muscle function and increased serum TC utilization than SR alone. SR+EX reduced P62 levels, increased glucose transporter type 4 and peroxisome proliferator-activated receptor γ coactivator-1α protein expression, and improved grip strength relative to the high-fat and high-sucrose liquid (HFHS) group, and this was not observed in the HFHS+EX group. Conclusion SR induced mitophagy-related protein expression in quadriceps, without affecting muscle function. And, the combination of SR and EX activated mitophagy-related proteins and improved muscle function.

Objective To explore the application value of monoexponential, biexponential models multiple b values diffusion weighted imaging(DWI) in distinguishing pancreatic cancer from non-tumorous pancreas.Methods Subjects comprised 37 pancreatic cancers confirmed by clinical or surgery.Pancreas multiple b values DWI was performed using 3.0T scanner.Standard apparent diffusion coefficient (ADCstandard) was calculated using monoexponential diffusion model.Pure diffusion coefficient (ADCslow), pseudodiffusion coefficient (ADCfast) and perfusion fraction (f) were calculated using intravoxel incoherent motion(IVIM) diffusion model.Parameters of pancreatic cancers and non-tumorous pancreas were compared using independent samples t test.Results Mean ADCslow value of pancreatic cancer was higher than that of non-tumorous pancreas (0.611×10-3 mm2/s vs 0.521×10-3 mm2/s,P=0.037).Mean ADCfast and f values of pancreatic cancer were lower than that of non-tumorous pancreas (5.066×10-3 mm2/s vs 7.188×10-3 mm2/s,P=0.035;55.8% vs 64.0%,P=0.016;respectively).ADCslow of pancreatic cancer was positively correlated to ADCstandard (r=0.824,P=0.000).ADCfast of pancreatic cancer was negatively correlated to f(r=-0.558,P=0.000).Conclusion ADCslow, ADCfast and f derived from IVIM-DWI model can distinguish pancreatic cancer from non-tumorous pancreas.IVIM-DWI may be a promising and non-invasive tool for early diagnosing and differentiating pancreatic carcinoma from non-tumorous pancreas.

The purpose of this study is to reveal the role of Girdin in regulating the aggregation of actin filaments by studying the relationship between PKB/Akt and Girdin. First we used Scansite software (http://scansite.mit.edu) to predict relevant target sites of PKB/Akt on mouse Girdin. To gain insight into the role of phosphorylation of Girdin by PKB/Akt, we assessed the location of phosphorylated Girdin in fertilized eggs by staining with anti-P-Girdin 1 417 Ab. We detected a distinct increase in the fluorescence signal of F-actin and P-Girdin 1 417 after microinjection of Akt WT and myr-Akt. The addition of myr-Akt induced phosphorylation of Girdin in mouse fertilized eggs. In addition, siRNA-mediated Akt-knockdown blocked phosphorylation of Girdin. The distribution of actin filaments was obviously scattered. These results strongly suggest that PKB/Akt could directly phosphorylate Girdin on Ser1 417 and promote its function in mouse fertilized eggs.
Actins ; physiology ; Animals ; Mice ; Microfilament Proteins ; physiology ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; physiology ; RNA, Small Interfering ; Vesicular Transport Proteins ; physiology ; Zygote