Objective: To explore the causal association between dietary components (carbohydrate, fat, protein, and sugar) and 119 genera of known gut microbiota using Mendelian randomization (MR) methods. Methods: Genome-wide association study (GWAS) data for dietary components were collected from the DietGen, while GWAS data for gut microbiota were collected from the MiBioGen. Single nucleotide polymorphism (SNP) loci associated with the four dietary components were used as instrumental variables, and 119 known gut microbiota genera were used as the outcomes. MR analysis was performed using inverse variance weighted (IVW) method. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy and exclude outliers were tested using MR-Egger regression and MR-PRESSO test. Common genetic pleiotropic genes between dietary components and gut microbiota were identified by MAGMA and PLACO analyses. Results: The MR analysis revealed causal associations between carbohydrates and 4 gut microbiota genera, fats and 14 genera, proteins and 14 genera, and sugars and 11 genera (all P<0.05). The MR-Egger regression analysis showed no horizontal pleiotropy among the selected SNPs, and the MR-PRESSO test did not identify any outliers (all P>0.05). The MAGMA and PLACO analyses revealed that 74.42% (32/43) of the causal associations had pleiotropic genes, with 1 to 10 pleiotropic genes identified. Multiple causal association groups shared the same pleiotropic genes. Conclusion There are potential genetic and causal associations between dietary components and gut microbiota.

Objective To prepare tubeimoside Ⅲ nanoemulsion(TBMⅢ-NE)and evaluate its adjuvant effect in vaccines.Methods TBMⅢ-NE was prepared using low-energy emulsification.Dynamic light scattering was used to characterize the particle size and polydispersity index of the obtained TBMⅢ-NE,and transmission electron microscopy(TEM)was employed to observe the morphology.CCK-8 assay was utilized to determine the cytotoxicity of TBMⅢ-NE on bone marrow-derived dendritic cells(BMDCs).The in vitro safety of TBMⅢ-NE was evaluated using a hemolysis assay.The ability of TBMⅢ-NE to promote the phagocytosis of antigens by DC2.4 cells was observed using confocal laser microscopy.After co-incubation of TBMⅢ-NE with BMDCs,the expression levels of CD40,CD86,MHC-Ⅰ,and CCR7 on the surface of BMDCs were detected using flow cytometry,and the levels of cytokines in the supernatant of BMDCs were measured using enzyme-linked immunosorbent assay(ELISA).After female BALB/c mice were immunized with the SARS-CoV-2 antigen RBD in combination with TBMⅢ-NE,ELISA was conducted to determine the serum levels of specific IgG,IgG2a,and IgG1 antibodies.The number of specific IFN-γ-secreting cells in mouse splenocytes was detected using enzyme-linked immunospot(ELISpot)assay.Results The prepared blank nanoemulsion(BNE)and TBMⅢ-NE were in a particle size of 25.46 and 25.89 nm,and a polydispersity index of 0.214 and 0.125,respectively.TEM displayed that TBMⅢ-NE was in uniform sphere and well dispersed.When the TBMⅢ-NE adjuvant was diluted by 400-fold,the survival rate of BMDCs was approximately 86%.Compared with free TBMⅢ,the hemolytic toxicity of TBMⅢ-NE was significantly reduced(P<0.01).TBMⅢ-NE promoted the phagocytosis of antigens by DC2.4 cells and significantly increased the expression of CCR7 on the surface of BMDCs(P<0.05),indicating its potential to promote more dendritic cells to effectively migrate to lymph nodes.TBMⅢ-NE also promoted the expression of IL-6 and IL-1β in the supernatant of BMDCs(P<0.05).When combined with RBD,TBMⅢ-NE significantly increased the levels of specific IgG,IgG2a,and IgG1 antibodies in mouse serum(P<0.01)and promoted the secretion of specific IFN-γ in splenocytes(P<0.01),indicating that TBM Ⅲ-NE could enhance specific cellular immune responses.Conclusion A stable and highly effective TBMⅢ-NE that can induce humoral and cellular immune responses is successfully prepared.

Objective To investigate the interaction between a novel antimicrobial compound,HL-J6,and penicillin-binding protein 1(PBP1)of Staphylococcus aureus.Methods With MRSA252 genomic DNA as the template and PBP1F and PBP1R as primers,the expression plasmid pET30a-pbp1-39-608 was constructed by amplifying the target gene fragment followed by cloning into the Nde I/Xho I restriction sites of the pET30a vector.Then the obtained plasmids were transformed into Escherichia coli for the expression of PBP1-39-608 protein,and the product was purified by affinity chromatography.The inhibitory effect of HL-J6 on the transpeptidase activity of PBP1-39-608 was measured using peptidoglycan side chain backbone peptide,with thiol ester analog S2d as the substrate.The affinity between HL-J6 and PBP1-39-608 was detected using microscale thermophoresis(MST),and the binding interaction was confirmed by cellular thermal shift assay(CETSA).Molecular docking and dynamics simulation were performed using AutoDock Vina and Desmond software,respectively,to elucidate the binding mode of HL-J6 with the PBP1-39-608 protein and the key amino acid residues involved.Results The recombinant plasmid pET30a-pbp1-39-608 was successfully constructed,and PBP1-39-608 protein was produced after induction and purified,yielding a protein with an approximate molecular mass of 65×103.HL-J6 inhibited the transpeptidase activity of PBP1-39-608 in a time-dependent manner(P<0.001).The dissociation constant Kd of the binding between HL-J6 and PBP1-39-608 was 64.92 μmol/L.Molecular docking results showed that HL-J6 bound to the active pocket of PBP1-39-608 by interacting with key residues such as ILE-348,ASN-370,THR-516 and PHE-423,with a binding score of-8.38 kcal/mol(<-5.00 kcal/mol).Dynamics simulation results indicated that the complex became stable after 50 ns.Conclusion HL-J6 effectively inhibits the transpeptidase activity of Staphylococcus aureus PBP1,and shows stable interaction with the protein.

In order to further strengthen the training and management of clinical teachers, broaden the career development channels of clinical teachers, and truly stimulate their teaching enthusiasm and initiative, this study further classifies clinical teachers according to the principle of the Snell model, focuses on the training of educational clinicians, and explores the training mechanism of teaching talents in line with the actual development needs of hospitals affiliated to universities from the aspects of selection, training, incentive, and assessment. The results of practice show that related practices have a good effect, and the mean number of teaching achievements was 1.98 for the 56 educational physicians, which was 3.9 times that for non-educational physicians. The per capita teaching achievements of educational physicians tended to increase every year compared with those of non-educational physicians. The training path for educational physicians provides useful experience for the construction of clinical teaching team and the high-quality development of education and teaching, and at the same time, it is necessary to further strengthen the dynamic adjustment of talent echelon, the improvement of operating mechanism, and the introduction of new technology.

Objective:To explore the clinical characteristics, diagnosis and treatment of secondary adrenocortical insufficiency(SACI)after kidney transplantation.Methods:Retrospective analysis was conducted for clinical data of 12 recipients with SACI after transplantation from March 2018 to November 2019(observation group). Meanwhile, 10 healthy subjects(control group)were randomly selected for in-hospital physical reexaminations during the same period. General data and morning cortisol levels of adrenocorticotropic hormone(ACTH)and aldosterone were compared between two groups.Results:In observation group, there were 8 male and 4 female with an average age of (43.67±8.81) years. Six cases(50.0%)of SACI occurred during recovery period within 30 days and 3 cases(25.0%)within 30 to 90 days post-transplantation. Deceased citizen donation(DCD)was performed in 9 cases(75.0%)and re-transplanted in 3 cases(25.0%). Oral immunosuppressive regiments were administered in a low-dose prednisone-based triple/quadruple regimen. The mean eGFR of observation group was(54.08±20.03)ml/min. The first patient had adrenal crisis, the fourth had sole symptom of fatigue and the remainder stayed asymptomatic. All of them had persistent hyperkalemia and hyponatremia. The average level of plasma cortisol was(62.24±24.16)mmol/L and it was much lower than normal in all patients at 8 am. The determination of plasma ACTH at 8 am showed that 7 patients(58.33%)were lower than normal and the remaining 5 slightly surpassed the low limit of normal. The average level of plasma cortisol at 8 am was significantly lower in observation group than that in control group(141.34±26.28)nmol/L( t=-7.349, P<0.001). The average ACTH level of observation group at 8 am was(1.08±0.515)pmol/l and it was significantly lower than that of control group(2.53±1.06)pmol/L( t=-4.178, P<0.001). The level of aldosterone was normal in both groups and showed no significant difference. All patients in observation group received an intravenous injection of hydrocortisone with satisfactory outcomes. Conclusions:Transplant surgeons should be on a high alert for an occurrence of SACI in renal transplant recipients. Serum potassium and sodium levels may be the predictors of SACI.

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. We found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery (pre-berberine) or direct addition into injured cecum immediately after the surgery (inter-berberine). Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary adhesion. The dysregulated TIMP-1/MMP balance was observed in patients after surgery, as well as adhesion tissues from primary adhesion or adhesion reformation rats. Inter-berberine treatment had a better effect for adhesion reformation prevention than Interceed. Berberine promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core, which was reversed by TIMP-1 overexpression in fibroblasts. In conclusion, this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.

Objective: To analyze the epidemiological characteristics of coronavirus disease 2019 ( COVID-19 ) in Shaoxing from January 23 to March 31, 2020, so as to provide basis for the prevention and control of COVID-19. Methods: The information of the COVID-19 cases in Shaoxing were collected from the National Diseases Prevention and Control Information System and the field investigation by CDCs. A descriptive analysis was used for the epidemiological characteristics, including time, spatial and population distribution, clinical features and exposure history. Results: Totally 42 confirmed cases of COVID-19 were reported by March 31, without deaths. The first case was reported on January 23 and the last one was on February 13. The onset of cases peaked in mid-to-late January. All the counties ( cities or districts ) had confirmed cases, 14 cases were reported in Yuecheng District. Twenty-five ( 59.52% ) cases were 45 years old or over. Thirteen ( 30.95% ) cases were engaged in business and eight ( 19.05% ) cases were unemployed. No cases were found among medical staff. The main clinical symptoms were fever, dry cough, fatigue and imaging features of pneumonia, with nine ( 21.43% ) severe cases and three ( 7.14% ) critical cases. There were 34 ( 80.95% ) imported cases, who mainly came from Hubei Province. Totally 1 955 close contacts were tracked down, among whom 4 cases were confirmed, with the infection rate of 0.20%. Conclusions The COVID-19 cases reported in Shaoxing were mainly aged 45 years or over, severe and imported from Hubei Province. There was no continuous transmission in the community, and no infection in medical staff or deaths.

Objective:To investigate the application value of three-dimensional visualization technology in management of middle hepatic vein (MHV) processing in associating liver partition and portal vein ligation for staged hepatectomy(ALPPS).Methods:The retrospective and descriptive study was conducted. The clinical data of 40 patients with right massive liver cancer or multiple right liver lesions who underwent ALPPS in the First Affiliated Hospital of Guangxi Medical University from November 2017 to August 2019 were collected. There were 34 males and 6 females, aged (44±9)years, with a range from 26 to 64 years. All patients underwent multi-slice computed tomography (CT) plain and enhanced scan of superior abdominal region before operation, and the data were transmitted to the liver visualization analysis software IQQA system with 1.5 mm thin-layer images to complete the three-dimensional reconstruction of the liver and its blood vessels. Patients were performed ALPPS based on results of three-dimensional reconstruction and intraoperative findings. Observation indicators: (1) results of preoperative three-dimensional reconstruction; (2) surgical situations; (3) follow-up. Follow-up was conducted using outpatient examinations and telephone interview to detect postopeartive survival of patients up to March 2020. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were described as M (range). Count data were represented as absolute numbers. Results:(1) Results of preoperative three-dimensional reconstruction: 40 patients underwent three-dimensional reconstruction successfully, of which 37 clearly showed MHV, tumor location and relationship between them, 3 patients showed unclearly MHV and were classified based on two-dimensional images. Of the 40 patients, 12 had MHV classified as type A, 13 as type B, 9 as type C, and 6 as type D. Three-dimensional reconstruction of vessels showed 22 with umbilical veins and 9 with anterior veins. Of the 40 patients, 35 were predicted to preserve MHV, and 5 were predicted to resect MHV. Total estimated liver volume, tumor volume, and reserved liver volume were (1 012±119)cm 3, 600 cm 3(8-2 055 cm 3), (346±80)cm 3. The ratio of future liver remnant to standard liver volume was 34%±8%. (2) Surgical situations : 40 patients underwent the first-stage ALPPS, including 35 with preservation of MHV and 5 with resection of MHV, which was accorded with preoperative prediction. Thirty-four patients underwent the second-stage ALPPS, and 6 patients had failure to receive the second-stage ALPPS due to undificiency future liver remnant. The operation time and volume of intraoperative blood loss for 40 patients undergoing first-stage ALPPS were (350±79)minutes and 300 mL(range, 100-2 600 mL). Three patients received blood transfusion and no perioperative death occurred. There were 24 patients with grade A heptic insufficiency according to criteria of International StudyGroup of Liver Surgery (ISGLS) and 16 patients with grade B heptic insufficiency after the first-stage ALPPS. Twenty-eight patients had grade Ⅰ complications of Clavien-Dindo classification, including 17 with a small pleural effusion, 10 with a small pleural and abdominal effusion, 1 with hypoproteinemia; 8 patients had grade Ⅱ complications of Clavien-Dindo classification, including 5 with pneumonia, 1 with pneumonia combined with pleural and abdominal effusion, 1 with coagulation disorders, 1 with biliary fistula; 3 patients had grade Ⅲ complications of Clavien-Dindo classification, including 2 with pneumothorax and pneumonia, 1 with pneumothorax, pneumonia and coagulation disorders; 1 patient had grade Ⅳ complications of Clavien-Dindo classification as systemic inflammatory response syndrome. All patients with complications were improved after symptomatic treatment, anti infection, transfusion of fresh frozen plasma or drainage. For the 34 patients undergoing the second-stage ALPPS, the operation time and volume of intraoperative blood loss were (320±83)minutes and 500 mL(range, 200-6 000 mL). Twelve patients received blood transfusion. There were 12 patients with grade A heptic insufficiency according to criteria of ISGLS and 22 with grade B heptic insufficiency after the second-stage ALPPS. Eighteen patients had grade Ⅰ complications of Clavien-Dindo classification, including 11 with a small pleural effusion, 7 with a small pleural and abdominal effusion; 12 patients had grade Ⅱ complications of Clavien-Dindo classification, including 4 with pneumonia, 4 with coagulation disorders, 3 with massive abdominal effusion, 1 with biliary fistula; 3 patients had grade Ⅲ complications of Clavien-Dindo classification, including 1 with pneumothorax and pneumonia, 1 with massive pleural effusion, 1 with obstructive jaundice; 1 patient had grade Ⅳ complications of Clavien-Dindo classification as pneumonia and anemia. All patients with complications were improved after symptomatic treatment, anti infection, transfusion of fresh frozen plasma or drainage. (3) Follow-up: 40 patients were followed up for 2-35 months, with a median follow-up time of 17 months. The 6-month, 1-, and 2-year survival cases were 35, 26, 21 cases. Conclusion:Three-dimensional visualization technology can clearly show the MHV classification and its relationship with tumor location, which has an important guiding significance in the decision-making of MHV management in ALPPS.

Objective To explore whether therapeutic dosing timing of proteasome inhibitor bortezomib(BZ) would impact its clinical efficacy .Methods From 2012 to 2018 ,35 biopsy-confirmed cases of acute antibody-mediated kidney transplant rejection (AMR) were collected .They received intravenous immunoglobulin (IVIG) plus sirolimus (Sir) plus bortezomib (BZ) .Three groups were assigned according to dosing timing of BZ .After a diagnosis of AMR ,ET (early treatment ) group began BZ dosing within 7 days (n=16) while DT (delayed treatment) group within 8-14 days (n=11) and LT (late treatment) group > 14 days (n= 8).Their clinical parameters and incidence of complications were analyzed .Results DSA reversal rate of ET ,DT and LT groups was 87 .5％ , 45 .5％ and 25 .0％ (P=0 .006) while DSA declining rate 93 .8％ ,90 .9％ and 50％ respectively (P=0 .019);recurrent rate of AMR was lower in ET/DT group than LT group (6 .6％ vs 10％ vs 75％ , P=0 .042) .No significant differences existed in blood perfusion score of allograft at 1 month post-dosing among three groups .In three groups ,creatinine (Cr) of ET group was lower than DT group at month 1/3/12 while DT group was lower than LT group .No significant difference existed in the incidence of adverse reactions among 3 groups .Conclusions More likely to enter the window period , early dosing of BZ is more effective for treating acute AMR .An earlier intervention yields a better efficacy .

Objective To describe the experiences when different methods were used to treat early-onset antibody-mediated rejection (AMR) after kidney transplantation.Methods The clinical data of 42 recipients who experienced early-onset acute AMR after kidney transplantation in our department from Jan.2010 to Apr.2016 were retrospectively analyzed.The recipients were divided into 3 groups based on different strategies against AMR:group A (plasma exchange with intravenous immunoglobin);group B (bortezomib solo),and group C (combination of bortezomib and sirolimus).Results All the AMR episodes were diagnosed by kidney biopsy 9-27 days after transplantation.The AMR reversal rate in groups B and C was significantly higher than that in group A (100％ versus 60.00％,P=0.034;100％ versus 60.00％,P=0.007).The AMR recurrence rate in groups B and C was significantly lower than that in group A (0 versus 41.67％,P =0.035;0 versus 41.67％,P =0.007).The recipient survival rate was 100％ in all the three groups.There were 11 graft losses in group A,and none in group B or C.The graft survival rate in group B at 6 months,1 year and 3 years was significantly higher than in group A (100％ versus 60.00％,P =0.034;100％ versus 55.00％,P =0.021;100％ versus 50.00％,P =0.013).The graft survival rate in group C at 6 months and 1 year was significantly higher than in group A (100％ versus 60.00％,P =0.007;100％ versus 55.00％,P =0.003).There was no significant difference in AMR reversal rate,AMR recurrence rate and graft survival rate between groups B and C.There was no significant difference in incidences of infection,hyperlipidemia and bone marrow suppression among the three groups.The incidence of diarrhea in groups B and C was significantly higher than in group A (50.00％ versus 0,P =0.001;42.86％ versus 0,P =0.001).The incidence of peripheral neuritis in group B was significantly higher than in group A (25.00％ versus 0,P =0.02),but similar to group C.There was no significant difference in average serum creatinine level among three groups within 1 year after treatment (P＞ 0.05).Antibodies against human leukocyte antigen (HLA) and donor specific antibodies were detected in all the 42 recipients before treatment.The negative conversion ratio of panel reactive antibody (PRA) in group A was significantly lower than in groups B and C (10.00％ versus 87.50％,P＜ 0.001;10.00％ versus 92.86％,P ＜ 0.001).The PRA recurrence rate in group A was significantly higher than in groups B and C (85.00％ versus 37.50％,P＜0.001;85.00％ versus 0,P＜0.001),while that in group B was significantly higher than in group C (37.50％ versus 0,P =0.014).The ratio of Treg in peripheral blood at 3-12 month after treatment in group C was significantly higher than in groups A and B (P＜0.05).Conclusion Treatment for early-onset AMR after kidney transplantation based on bortezomib might be an effective and safe strategy.Graft longterm survival might benefit from the combination of bortezomib and sirolimus.