Objective To explore the role and mechanism of warm malate ringer's solution(MR)in resuscitation of the lethal triad caused by severe trauma.Methods A rat model of severe trauma was established in SPF-grade SD rats(half male and half female,weighing 200～220 g)using combined multiple injuries and hemorrhagic shock,and the rats were randomly divided into 8 groups(n=8):Sham group,only arterial and venous catheterization;Trauma(Tra)groups with different time points(10,30,60,90,120,180 min)and a Trauma group that were observed without any treatment for 180 min after model establishment.The changes of activated clotting time(ACT),reaction time(R),maximum amplitude(MA),and rate of blood clot formation(Angle)at different time points were detected by using thromboelastography,and tail bleeding,core body temperature and arterial blood gas parameters,were also observed and detected.The plasma von Willebrand Factor(vWF)level,mitochondrial respiratory control ratio in pulmonary venous endothelium,and expression levels of vascular endothelial cadherin(VE-Cadherin),peroxisome proliferator activating receptor gamma coactivator 1α(PGC1α),dynamin-related protein 1(Drp1),p-Drp1,and mitofusin 2(Mfn2)were detected to evaluate the vascular endothelial injury and mitochondrial dysfunction.Another group of SD rats were randomly divided into severe trauma group(no treatment for 180 min after injury),and MR solution at room temperature and at 37 ℃ groups.MR solution at room temperature or at 37 ℃ was given to the rats using a medical blood transfusion apparatus at 60 min post-trauma.Above indicators were observed and detected to investigate the resuscitation effect of the MR solution.Results Compared with the Sham group,the severely traumatic rats at 180 min after injury had significantly prolonged ACT and R values(P＜0.05),shortened MA and decreased Angle values(P＜0.05),extended tail bleeding time(P＜0.05),lower partial pressure of carbon dioxide(PCO2)and HCO3-and base excess(BE)levels(P＜0.05),and continuously increasing K+(P＜0.05)and decreasing Na+(P＜0.05)and Ca2+levels(P＜0.05).Additionally,plasma vWF level(P＜0.05)and protein levels of VE-cadherin,PGC1α and Mfn2 in pulmonary vein endothelium were significantly reduced(P＜0.05),the expression of p-Drp1 was enhanced and the mitochondrial respiration control rate was declined in the rats at 180 min after injury(P＜0.05).MR solution resuscitation shortened tail bleeding time(P＜0.05),increased core body temperature(P＜0.05),elevated plasma vWF level(P＜0.05),increased protein levels of VE-cadherin,PGC1α and Mfn2(P＜0.05),and decreased that of p-Drp1 protein expression(P＜0.05)when compared with the rats at 180 min after severe traumatic injury.The above effects were more significant in the rats infused with the solution at 37 ℃ than those at room temperature.Conclusion Warm MR solution significantly improves the lethal triad in rats after severe trauma,which may be associated with its improving mitochondrial function and attenuating vascular endothelial damage.

Objective To detect the expression of translationally-controlled tumor protein 1(TPT1)in renal cell carcinoma(RCC)and to explore its role in RCC.Methods Microarray dataset GSE15641(including 23 normal kidney tissue samples and 32 RCC tissue samples)was downloaded from the Gene Expression Omnibus,and differentially expressed genes between RCC tissue and normal kidney tissue were screened using R 4.3.0 software.The TPT1 expression in RCC tissue and adjacent non-tumor tissue of 90 patients diagnosed and treated at Affiliated Hospital of Nantong University,as well as in human RCC cells(769-P,786-O,ACHN,and Caki-1)and human embryonic kidney 293 cell(HEK293)was detected by quantitative polymerase chain reaction(qPCR)and Western blotting.The relationship between TPT1 expression and clinical pathological characteristics of RCC patients was analyzed by χ2 test.The clinical data of 522 RCC patients were derived from The Cancer Genome Atlas,and the correlation between TPT1 expression and prognosis of RCC patients was analyzed by receiver operating characteristic(ROC)curve and Kaplan-Meier survival curve.After in vitro transfection of TPT1 small interfering RNA(siRNA)and its negative control(NC)into 786-O and Caki-1 cells,the TPT1 expression was detected by qPCR and Western blotting;the proliferation,migration,and invasion were detected by cell counting kit 8 assay,scratch assay,and Transwell assay,respectively;and the expression of apoptosis-related proteins was detected by Western blotting.Results TPT1 expression was significantly upregulated in the RCC tissue and cells compared with the normal kidney tissue and HEK293 cells(all P＜0.05).The RCC patients with low TPT1 expression levels had significantly smaller tumor size and lower metastasis rate than those with high TPT1 expression levels(both P＜0.05).The ROC curve analysis results indicated that TPT1 had high diagnostic value for RCC(area under curve was 0.856 9,95%confidence interval was 0.804 5-0.909 3,P＜0.001).The Kaplan-Meier survival analysis results showed that the overall survival of RCC patients in the low TPT1 expression group was significantly longer than that in the high TPT1 expression group(P=0.018 4).In the cell experiment,compared with the siRNA NC group,the proliferation activity,scratch healing rate,and invading transmembrane cell number of 786-O and Caki-1 cells were significantly decreased after transfection with TPT1 siRNA(all P＜0.01);the expression levels of B-lymphoma gene 2(Bcl-2)and matrix metalloproteinase-9 were significantly decreased,while the expression of Bcl-2 associated X protein was significantly increased(all P＜0.05).Conclusion TPT1 is involved in the progression of RCC and may be a potential therapeutic target for RCC.

Objective To investigate the clinical significance of dynamic changes in the expression levels of tumor associated autoantibody(TAAB),including tumor protein 53(p53),protein gene product 9.5(PGP9.5),SRY-box containing gene 2(SOX2),G antigen 7 ATP-dependent RNA helicase(GAGE7),ATP-dependent RNA helicase(GBU4-5),melanoma antigen A1(MAGE A1),cancer/testis antigen(CAGE)in non-small cell lung cancer(NSCLC)patients before and after surgery.Methods Forty-one patients with NSCLC who underwent surgical treatment at the Department of Thoracic Surgery of Li Huili Hospital,Ningbo Medical Center,were selected from January 2019 to August 2022.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression levels of seven TAAB markers in the serum of 41 NSCLC patients undergoing surgical treatment.Results The expression levels of PGP9.5 were found to be significantly higher in the squamous cancer group than in the adenocarcinoma group(P<0.05),while the expression levels of GAGE7 were found to be significantly higher in the adenocarcinoma group than in the squamous cancer group(P<0.05).The expression level of GBU4-5 was found to be significantly higher in the squamous carcinoma group than in the adenocarcinoma group at one week after surgery(Z=-2.095,P=0.036).Within the adenocarcinoma group,the expression levels of GBU4-5(P=0.027)and CAGE(P=0.042)were found to be significantly lower at one week after surgery compared with those before surgery.The expression levels of PGP9.5(P=0.004),GAGE7(P<0.001),and GBU4-5(P=0.014)were found to have decreased significantly at six months postoperatively in comparison to their preoperative levels.In the squamous cancer group,no statistically significant differences were observed in the expression levels at one week after surgery.The expression level of SOX2(P=0.011)exhibited a statistically significant decrease at six months postoperatively in comparison to the preoperative levels.Similarly,the expression level of GBU4-5 was found to be significantly decreased at one week postoperatively in comparison to the preoperative levels(P=0.009).The expression levels of PGP9.5(P=0.003),GAGE7(P=0.001),and GBU4-5(P=0.013)were found to have decreased significantly at six months postoperatively.Conclusion Surgical intervention can reduce the expression level of 7 TAABs in NSCLC patients.Monitoring 7 TAABs before and after surgical treatment is helpful to predict the surgical efficacy and postoperative disease progression of NSCLC patients.

Objective To investigate the relationships of serum angiopoietin-like protein 4 (ANGPTL4) and fibroblast growth factor-23 (FGF-23) levels with the severity and prognosis of patients with diabetic nephropathy. Methods A total of 120 patients (diabetic nephropathy group) with diabetic nephropathy were selected from July 2018 to July 2020 and divided into mild group (n=62) and severe group (n=58) according to the staging criteria of diabetic nephropathy; based on the prognosis within 3 years, they were also divided into good prognosis group (n=94) and poor prognosis group (n=26). Additionally, 102 diabetic patients were enrolled as diabetic group, and 81 healthy volunteers were selected as control group. The serum levels of ANGPTL4 and FGF-23 in diabetic nephropathy patients were detected by enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to analyze the influencing factors of prognosis, and receiver operating characteristic (ROC) curves were drawn to analyze the values of ANGPTL4, FGF-23 and their combination in assessing the severity and prognosis of diabetic nephropathy. Results The levels of ANGPTL4 and FGF-23 in the diabetic nephropathy group and simple diabetic group were significantly higher than those in the control group (P < 0.05); compared with the simple diabetic group, the levels of ANGPTL4 and FGF-23 in the diabetic nephropathy group were significantly increased (P < 0.05); the levels of ANGPTL4 and FGF-23 in the severe group were significantly higher than those in the mild group (P < 0.05); the ROC curve analysis revealed that the areas under the curve (AUCs) for assessing disease severity of ANGPTL4, FGF-23 and their combination were 0.748, 0.781 and 0.858 respectively, and the combined diagnosis was significantly better than FGF-23 (Z=2.149, P=0.032) and ANGPTL4 (Z=2.886, P=0.004) alone; the levels of ANGPTL4 and FGF-23 in the good prognosis group were significantly lower than those in the poor prognosis group (P < 0.05); significant differences were observed in diabetes duration, blood urea nitrogen (BUN), serum creatinine (Scr), fasting blood glucose (FBG), glycated hemoglobin (HbA1C), hypertension, ANGPTL4 and FGF-23 levels between diabetic nephropathy patients with different prognoses (P < 0.05); the Scr, ANGPTL4 and FGF-23 levels were all risk factors affecting the prognosis of diabetic nephropathy (P < 0.05); the ROC curve analysis for prognosis assessment showed that the AUCs of ANGPTL4, FGF-23 and their combination were 0.774, 0.795 and 0.874 respectively; the combined diagnosis was significantly better than FGF-23 (Z=2.385, P=0.171) and ANGPTL4 (Z=2.317, P=0.021) alone. Conclusion The serum levels of ANGPTL4 and FGF-23 are significantly increased in diabetic nephropathy patients, and they have certain reference value for the clinical diagnosis and prognosis assessment of diabetic nephropathy patients.

Objective To observe the ameliorative effect of inhibiting acetyl-CoA carboxylase 2(ACC2)on cardiac dysfunction in septic mice and investigate its underlying mechanism.Methods Mouse model of sepsis was established by cecal ligation and perforation.A total of 24 male C57BL/6 mice(aged 8 weeks,weighing 20～25 g)were divided into sham operation group,sepsis group and ND-630+sepsis group.The cardiac specific ACC2 knockout(ACC2△CM)mice were constructed by Cre-LoxP recombinase system,and ACC2flox/flox Myh6-Cre-(ACC2fl/fl)mice were used as control.Several genetically engineered mice(8 weeks old,20～25 g,male)were divided into ACC2fl/fl+sham operation group,ACC2fl/fl+sepsis group,ACC2△CM+sepsis group,ACC2△CM+Mal-CoA+sepsis group,and ACC2△CM+sham operation group according to the random number table method.The contractile function and myofilament calcium sensitivity of cardiomyocytes were measured by a cell microtensiometer.Western blotting was used to detect the expression level of ACC2,and ELISA was employed to measure the level of malonyl-CoA(Mal-CoA)in myocardial tissue.The survival of the mice in 36 h after sepsis was observed.Results Compared with the sham operation group,the contraction amplitude of cardiomyocytes in sepsis group was decreased markedly,and the calcium sensitivity decreased significantly as well(P＜0.05).Based on the ACC2fl/fl+sham operation group,the ACC2△CM+sepsis group showed significant improvement in myocardial contraction compared with the ACC2fl/fl+sepsis group,with the contraction amplitude of cardiomyocytes recovered by 48.1％,and significantly restored calcium sensitivity(P＜0.05).ACC2△CM+Mal-CoA+sepsis group showed a notable decrease in myocardial cell contraction amplitude and a significant decrease in calcium sensitivity when compared to the ACC2△CM+sepsis group(P＜0.05).Compared with the sepsis group,the contraction amplitude of cardiomyocytes in the ND-630+sepsis group increased significantly,and the calcium sensitivity of myofilament also increased(P＜0.05).The expression level of ACC2 protein in the myocardial tissue of mice in the sepsis group increased compared to the sham operation group(P＜0.05).The level of myocardial Mal-CoA in the sepsis group was higher than that in the sham operation group(P＜0.05);Mal-CoA level in the myocardium of ACC2△CM+sepsis group mice was lower than that of sepsis group(P＜0.05).The 36-hour survival rate of the ACC2△CM+sepsis group.mice was 37.5％higher than that of the ACC2fl/fl+sepsis group mice.(P＜0.05).Conclusion Inhibition of ACC2 exerts a protective effect on myocardial contractility and calcium sensitivity in septic mice by reducing Mal-CoA.

Objective:To observe the clinical efficacy of Qigui Tangtongning Granules in the treatment of diabetic peripheral neuropathy (DPN) with qi deficiency and blood stasis.Methods:Prospective cohort study. A total of 80 DPN patients with Qi deficiency and blood stasis in Endocrinology Department of the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2021 to May 2022 who met the inclusion criteria were divided into 2 groups by random number table method, with 40 cases in each group. The control group was treated with epalrestat on the basis of routine hypoglycemia, and the treatment group was treated with Qigui Tangtongning Granules on the basis of control group. Both groups were treated for 8 weeks. TCM syndromes were scored before and after treatment. Disease severity was assessed using the Toronto Clinical Scoring System (TCSS). The motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of median nerve and common peroneal nerve were detected by electromyography/induced potentiometer. Serum CRP, TNF-α and IL-6 were detected by ELISA, fasting blood glucose (FPG) and two hours post-meal blood glucose (2 hPG) were detected by automatic biochemical analyzer, and glycosylated hemoglobin (HbA1c) was detected by automatic HBA1C analyzer. Adverse reactions were recorded and clinical efficacy was evaluated.Results:The total effective rate was 95.0% (38/40) in the treatment group and 77.5% (31/40) in the control group, the difference between the two groups was statistically significant ( χ2=5.17, P=0.023). After treatment, the TCM syndrome score and TCSS score of the treatment group were significantly lower than those in the control group ( t=-3.19 and -7.63, P<0.01); Median nerve SNCV [(47.90±4.51) m/s vs. (44.76±3.72) m/s, t=3.40], MNCV [(53.79±3.65) m/s vs. (51.32±4.25) m/s, t=2.79] and common peroneal nerve SNCV [(44.21±2.08) m/s vs. (40.51±2.49) m/s, t=7.23], MNCV [(44.63±4.72) m/s vs. (41.36±4.87) m/s, t=3.05] were significantly higher than those in the control group ( P<0.01); FPG [(5.05±0.63) mmol/L vs. (7.05±1.23) mmol/L, t=-9.17], 2 hPG [(9.10±1.64) mmol/L vs. (12.19±2.61) mmol/L, t=-6.35], HbA1c [(6.79±0.90) % vs. (7.22±1.02) %, t=-2.02] were significantly lower than those in the control group ( P<0.01 or P<0.05); TNF-α [(15.75±5.44) ng/L vs. (32.01±5.33) ng/L, t=-13.51], hs-CRP [(2.58±0.80) mg/L vs. (3.79±1.04) mg/L, t=-5.83], IL-6 [(18.20±4.92) ng/L vs. (29.97±5.18) ng/L, t=-10.41] were significantly lower than those in the control group ( P<0.01). No obvious adverse reactions were observed in 2 groups during treatment. Conclusion:Qigui Tangtongning Granules combined with conventional Western medicine can improve nerve conduction velocity, reduce inflammation and improve clinical efficacy in DPN patients with Qi-deficiency and blood-stasis syndrome.

Fecal microbiota transplantation (FMT) refers to using the intestinal microorganisms present in the feces or processed feces from healthy people for treating various types of diseases, such as digestive and metabolic diseases. The rapid development of metagenomic and culturomic technologies in gut microbiome analysis provides powerful tools for the FMT research and its clinical applications. Metagenomics technologies comprehensively revealed the diversity and functions of gut microbiota under health and disease conditions, while culturomics technologies helped isolation and identification of "unculturable" bacteria in the human gut under conventional culture conditions. The combination of these two technologies not only enabled us better understand the FMT regularities of cause and effect in clinical practices, but also effectively promoted its applications. Considering the above advantages, this article summarized the applications of metagenomics and culturomics technologies in FMT and prospected its future development trend.
Humans ; Fecal Microbiota Transplantation ; Metagenomics ; Feces/microbiology* ; Gastrointestinal Microbiome ; Bacteria

Objective:To compare serum procalcitonin and fibrinogen degradation product levels between type 2 diabetes mellitus patients with Escherichia coli bloodstream and urinary tract infections. Methods:The clinical data of 82 type 2 diabetes mellitus patients with Escherichia coli infections who received treatment between December 2014 and December 2019 in the First Affiliated Hospital of Datong University (The Fifth People's Hospital of Datong) were retrospectively analyzed. These patients were assigned to bloodstream infection ( n = 40) and urinary tract infection ( n = 42) according to the way of Escherichia coli infection. Serum procalcitonin and fibrinogen degradation product levels, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, C-reactive protein, white blood cell count, D-Dimer level, antithrombin III activity, and electrolytes were determined and compared between the two groups. Correlation between procalcitonin and other variables was analyzed. Multiple linear regression analysis was performed with procalcitonin level as a dependent variable and other relevant indexes as independent variables. Results:Body temperature, white blood cell count, neutrophil count, monocyte count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, procalcitonin level, C-reactive protein level, fibrinogen degradation product level, and D-Dimer level in the bloodstream injection group were (39.49 ± 0.64) ℃, (14.92 ± 11.78) × 10 9/L, (13.39 ± 11.60) × 10 9/L, (0.72 ± 0.36) ×10 9/L, (14.86 ± 10.52), (199.15 ± 160.69), (22.81 ± 17.86) μg/L, (133.44 ± 63.63) mg/L, (49.71 ± 41.44) mg/L, (16.56 ± 12.20) mg/L, respectively, which were significantly higher than those in the urinary tract infection group [(37.12 ± 1.20) ℃, (9.04 ± 3.95) × 10 9/L, (6.25 ± 4.02) × 10 9/L, (0.42 ± 0.29) × 10 9/L, (3.67 ± 3.34), (120.01 ± 44.08), (4.46 ± 8.69) μg/L, (39.22 ± 22.16) mg/L, (3.81 ± 3.41) mg/L, (0.84 ± 0.75) mg/L), t = 7.356, 2.578, 3.162, 2.958, 5.538, 2.591, 2.810, 4.825, 2.902, 2.375, all P < 0.05]. Platelet count, lymphocyte count, blood sodium level and antithrombin Ⅲ activity in the bloodstream infection group were (167.50 ± 104.93) × 10 9/L, (1.06 ± 0.58) × 10 9/L, (130.89 ± 6.50) mmol/L, (57.88 ± 16.28)% , which were significantly lower than those in the urinary tract infection group [(239.40 ± 82.52)× 10 9/L, (2.14 ± 0.71) × 10 9/L, (138.46 ± 5.96) mmol/L, (90.11 ± 8.90)%, t = -2.853, -6.313, -4.046, -7.350, all P < 0.05]. Correlation analysis revealed that serum procalcitonin level was positively correlated with body temperature ( r = 0.387), white blood cell count ( r = 0.355), neutrophil count ( r = 0.368), C-reactive protein ( r = 0.605), fibrinogen degradation product level ( r = 0.616), D-Dimer level ( r = 0.486) (all P < 0.05), and it was negatively correlated with sodium level ( r = -0.319) and antithrombin Ⅲ activity ( r = -0.465) (both P < 0.05). Multiple linear regression analysis results revealed that fibrinogen degradation product level and body temperature were greatly correlated with procalcitonin level. Conclusion:Inflammatory indicators procalcitonin level, body temperature, white blood cell count, neutrophil count, C-reactive protein, fibrinogen degradation product level and D-Dimer level were remarkably higher in type 2 diabetes mellitus patients with Escherichia coli bloodstream infection than those in type 2 diabetes mellitus patients with Escherichia coli urinary tract infection. Procalcitonin level was greatly correlated with body temperature and fibrinogen degradation product level.

Objective To investigate the effect of whole body vibration training on biomechanics and Wnt3a protein expression of the femur. Methods Forty-eight female SD rats were randomly divided into sham operation group, osteoporosis group and whole body vibration group, 16 in each group. The bone morphometric parameters were measured by Micro-CT, mechanical parameters of bone structure and materials were measured by three-point bending test, protein expression of Wnt3a and β-catenin was measured by Western blotting, and gene expression of Wnt3a, β-catenin, cyclin D1 and tcf1 was detected by qRT-PCR. ResultsCompared with sham operation group, bone mineral density (BMD), bone volume fraction (BVF), trabecular number, trabecular thickness and cortical bone thickness in osteoporosis group were decreased, and trabecular space was increased; compared with osteoporosis group, BMD, BVF, trabecular number, trabecular thickness and cortical bone thickness in whole body vibration group were increased, and trabecular space was decreased. Compared with sham operation group, the maximum load, elastic load and deflection of osteoporosis group were significantly reduced; compared with osteoporosis group, the maximum load, elastic load and deflection of whole body vibration group were significantly increased. Compared with sham operation group, the maximum stress, elastic stress, maximum strain and elastic modulus in osteoporosis group decreased significantly; compared with the osteoporosis group, the elastic stress, maximum strain and elastic modulus in whole body vibration group increased significantly. Compared with sham operation group, Wnt3a, β-catenin protein and gene expression decreased, cyclin D1, tcf1 gene expression also decreased; compared with osteoporosis group, Wnt3a, β-catenin protein and gene expression increased, cyclin D1, tcf1 gene expression increased as well. Conclusions Whole body vibration training can improve biomechanical properties of the femur and expression of Wnt3a protein in osteoporotic rats. The research findings provide laboratory reference data for the prevention and treatment of osteoporosis by whole body vibration training.

【Objective】 To evaluate the effect of health publicity on plateletpheresis donation among college students in Beijing. 【Methods】 Plateletpheresis donor recruitment was carried out in a conventional way in 2016~2017 and by health publicity in 2018~2019 among college students in Beijing. The data, including the number of blood donations, blood collection units, the number of repeated donations, the rate of eligible donors and the discarding rate due to blood donation reactions, of two groups were collected and statistically analyzed. 【Results】 The number of plateletpheresis donation, the collection units of platelets and the number of repeated blood donation among college students in Beijing have increased since 2016. The rate of ineligible college students at pre-donation screening decreased from 10.97% in 2016~2017 to 8.51% in 2018~2019(P<0.05), and the discarding rate due to blood donation reactions decreased from 0.45% to 0.17%(P<0.05). Most plateletpheresis candidates failed in the blood routine testing. 【Conclusion】 Health publicity helped college students in Beijing better understand the process of plateletpheresis donation to a certain extent, which played a positive role in expanding blood donors and promoting the recruitment and retention of apheresis donors in Beijing.