ObjectiveTo explore the potential mechanism of Changji'an Formula （肠激安方） on intestinal permeability for rats with diarrhea-predominant irritable bowel syndrome （IBS-D） of liver depression and spleen deficiency syndrome by the microRNA-29b-3p （miR-29b-3p）/tumor necrosis factor receptor-associated factor 3 （TRAF3）/nuclear factor-κB （NF-κB）/myosin light chain kinase （MLCK） axis. MethodsTwenty-four 1-day-old male Sprague-Dawley （SD） suckling rats were selected， and the IBS-D rat model of liver depression and spleen deficiency syndrome was established via a three-factor method，i.e. maternal separation plus acetic acid stimulation and restraint stress， for 6 consecutive weeks. After successful modeling， the rats were randomly divided into a model group， pinaverium bromide group， low-dose and high-dose Changji'an Formula groups， with 6 rats in each group. Another 6 age-matched non-modeled SD rats were included as the control group. The low-dose and high-dose Changji'an Formula groups were given intragastric administration of Changji'an Formula solution at doses of 16.74 g/（kg·d） and 33.48 g/（kg·d）， respectively； the pinaverium bromide group received intragastric administration of pinaverium bromide tablets at 0.018 g/（kg·d）； and the control group was given distilled water at 10 ml/（kg·d） via intragastric gavage. The intervention was conducted once daily for 14 consecutive days. After the gavage treatment， the fecal water content of rats in each group was measured. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum levels of intestinal permeability indicators， including D-lactic acid （D-LA）， diamine oxidase （DAO）， and lipopolysaccharide （LPS）. Quantitative real-time polymerase chain reaction （qRT-PCR） was conducted to determine the mRNA expression levels of miR-29b-3p， TRAF3， tumor necrosis factor-α （TNF-α）， p65， p50， and MLCK in colonic tissues. Western Blot analysis was employed to detect the protein expression levels of TRAF3， TNF-α， p65， phosphorylated p65 （p-p65）， MLCK， myosin light chain （MLC）， phosphorylated MLC （p-MLC）， and tight junction proteins including junctional adhesion molecule-A （JAM-A）， Occludin， and Claudin-1 in colonic tissues. ResultsCompared with the control group， the model group exhibited significantly increased fecal water content and serum levels of D-LA， DAO， and LPS， along with decreased protein expression levels of JAM-A， Occludin， and Claudin-1 in colonic tissues （P＜0.05 or P＜0.01）. Additionally， in the model group， the mRNA expression levels of miR-29b-3p， TNF-α， p65， p50， and MLCK in colonic tissues were up-regulated， while the mRNA and protein expression levels of TRAF3 were down-regulated； the protein levels of TNF-α and MLCK， as well as the ratios of p-p65/p65 and p-MLC/MLC， significantly elevated （P＜0.01）. Compared with the model group， all treatment groups showed reduced fecal water content and serum levels of D-LA， DAO， and LPS， along with down-regulated mRNA expression levels of miR-29b-3p， TNF-α， p65， p50， and MLCK， and up-regulated TRAF3 mRNA expression in colonic tissues. Moreover， the pinaverium bromide group and high-dose Changji'an Formula group presented increased protein levels of Occludin， Claudin-1， and TRAF3， as well as decreased protein levels of TNF-α and MLCK， and reduced ratios of p-p65/p65 and p-MLC/MLC in colonic tissues （P＜0.05 or P＜0.01）. Compared with the low-dose Changji'an Formula group， the high-dose group had lower fecal water content and serum levels of DAO and LPS （P＜0.01）. In comparison with the pinaverium bromide group， the high-dose Changji'an Formula group showed a significant decrease in serum DAO level （P＜0.01）. ConclusionsChangji'an Formula can reduce intestinal permeability and restore intestinal barrier function in IBS-D rats of liver depression and spleen deficiency syndrome by regulating the miR-29b-3p/TRAF3/NF-κB/MLCK axis.

Objective To investigate the clinical effect of transhepatic arterial chemoembolization(TACE)combined with tyrosine kinase inhibitors(TKIs)and programmed death receptors-1(PD-1)inhibitors(TACE+TKIs+PD-1 antibody)in the treatment of moderate advanced unresectable hepatocellular carcinoma(HCC).Methods The clinical data of 65 patients with moderate advanced unresectable hepatocellular carcinoma admitted to the Affiliated Hospital of North Sichuan Medical College from January 2020 to January 2022 were analyzed retrospectively.65 patients were treated with TACE+TKIs+PD-1 antibody.The observation indexes were tumor response,objective response rate(ORR),disease control rate(DCR),total survival time,progression free survival time,conversion operation rate and adverse drug reaction.Results The ORR of 65 p-atients with hepatocellular carcinoma was 49.2％(32/65),and the DCR was 89.2％(58/65).Among them,there were 2 patients with complete remission(CR),30 patients with partial remission(PR),26 patients with stable disease(SD),and 7 patients with progression disease(PD).Among 65 patients with hepatocellular carcinoma,18 patients were transformed into resectable hepatocell-ular carcinoma and underwent RO surgery.The conversion rate was 27.6％(18/65).65 patients were followed up for 3 to 22.4 months,The median follow-up time was 16.5 months.The median overall survival time and median disease progression free survival time of 65 patients were 14.5 months(95％CI:12.3～16.6 months)and 8.8 months(95％CI:6.9～10.6 months),respectively.After treatment,65 patients all had post embolism syndrome(abdominal pain,fever,nausea,vomiting and other symptoms),and some patients had transient abnormal liver function.Adverse drug reactions below grade 3 recovered within a few days.Some patients were associated with multiple adverse drug reactions.1 patient(1.5％)stopped using TACE because of stubborn vomiting,and 5 patients(7.6％)stopped using Lenvatinib because of severe liver function damage during treatment,2 patients(3％)stopped using Camrelizumab because of severe reactive capillary hyperplasia,one patient(1.5％)stopped using Tislelizumab because of severe hypothyroidism,one patient(1.5％)stopped the treatment of Lenvatinib and Sintilimab due to severe gastrointestinal bleeding.The adverse drug reactions of grade 3～4 occurred in other patients were alleviated after drug reduction,symptomatic treatment and hormone treatment.Conclusion TACE+TKIs+PD-1 antibody can obtain reliable clinical efficacy and anti-tumor activity in the treatment of moderate advanced unresectable hepatocellular carcinoma.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the main pathogen that causes COVID-19,which is fast-mutating and highly transmissible.The infection has led to a global epidemic.As the main preventive and control measure,vaccination plays a critical role in fighting a-gainst COVID-19.Although a large number of epitope-based and mucosal vaccines have been stud-ied,few peptide epitope vaccines targeting the mucosa and their functional evaluation have been re-ported.In this study,we used SARS-CoV-2 structural protein M peptide epitope predicted by the IEDB database as an antigenic target to design the MS-3S gene containing 3 050 and 1 229 signal peptides and DCpep optimized for insertion into MS2 phage coat proteins.The expression plasmid pSIP:MS-3S was constructed by cloning the PCR fragments seamlessly and was transformed into Lactiplantibacillus plantarum 18 to obtain the recombinant bacterium LP18:MS-3S.Expression conditions such as induction time,inducer concentration,rotational speed and initial pH were opti-mized.The intranasal immunization experiments were performed to examine the vaccine efficacy.The results showed that the 916 bp-long target gene MS-3S modified and optimized was amplified and used to successfully construct the recombinant bacterial strain LP18:MS-3S.The optimal con-ditions for recombinant protein expression were obtained and verified by Western blot,flow cy-tometry,immunofluorescence and other detection methods.The optimal expression conditions were determined as follows:induction time was 4 h with 100 pg/L of SppIP as the optimal induction concentration.Antibody-specific for the epitope was verified by ELISA experiments in serum,alve-olar lavage fluid and fecal dilutions of mice.In summary,a recombinant bacterial strain expressing the epitope antigen of the SARS-CoV-2 M protein peptide was constructed.The obtained protein can induce the body to produce humoral and mucosal immunity,which lays the foundation for the development of a vaccine candidate for the mucosal immunity of COVID-19.

In recent years, a number of policies have been implemented to strengthen the cultivation of general practitioners in China. However, the development of community-level health professionals is still lagging behind, the development is uneven among regions, the overall number of general practitioners is insufficient, and the quality of medical services needs to be improved. Based on the Shanhai (Mountain and Sea) promotion project, with the close cooperation between the Second Affiliated Hospital and the medical consortium unit Suichang County People′s Hospital, a " Joint Cultivation by Dual-Teachers " model has been applied in training general practitioners for Suichang county community since March 2021. In this article we discuss the optimization and integration of medical and health resources through the outreaching assistance of high-quality personnel, management and system of medical service, to comprehensively upgrade the primary care and the quality of grass-roots general practitioners in remote mountainous areas.

Objective:To investigate the relationship between plasma fibrinogen (FBG) level and p53 protein expression of tumor tissue in breast cancer, and to study the relationship between the parameters of plasma FBG level and p53 protein expression in tumor tissue and the prognosis of breast cancer.Methods:A total of 177 breast cancer patients who underwent surgery in the Second Affiliated Hospital of Hainan Medical University between Jan. 2012 and Oct. 2016 were included in the study. The data, including the general clinicopathological characteristics, the expression of p53 protein with immumohistochemical (IHC) staining, and plasma FBG level within 1 week before surgery, were collected. Chi-square test was used to analyze the relationship between the different levels of plasma FBG and the parameters of general clinicopathological characteristics and p53 protein, and binary Logistic regression was used for multivariate analysis. Kaplan-meier survival analysis and COX regression analysis were used for univariate analysis and multivariate analysis of IDFS, respectively.Results:Univariate analysis showed that plasma FBG>2.75 g/L had significant positive correlation with age>50 and positive p53 expression in tumor tissue ( P values were <0.001 and 0.006, respectively) . Multivariate analysis showed that positive p53 expression in tumor tissue ( OR 2.256, 95% CI 1.192 to 4.271, P<0.001) and age>50 years ( OR 3.712, 95% CI 1.967 to 7.002, P<0.001) were independent correlation factors for plasma FBG>2.75 g/L. Kaplan-Meier survival analysis results showed that the aged>50 years, T>2 cm, lymph node metastasis, Ⅲ stage, plasma FBG>2.75 g/L, positive p53 expression in tumor tissue were adverse prognostic factors of IDFS. COX regression analysis results showed that plasma FBG>2.75 g/L ( HR 6.226, 95% CI 3.863 to 10.033, P<0.001) , positive p53 expression in tumor tissue ( HR 1.864, 95% CI 1.133 to 3.066, P=0.014) and Ⅲ stage ( HR 10.382, 95% CI 5.942 to 18.141, P<0.001) were adverse prognostic factors of IDFS, and adjuvant endocrine therapy ( HR 0.427, 95% CI 0.275 to 0.663, P<0.001) was a favourable prognostic factor for IDFS. Conclusions:The expression of p53 protein was significantly correlated with high plasma FBG level in breast cancer. Both p53 protein expression and high plasma FBG level are associated with poor prognosis of breast cancer. On the basis of traditional pathological prognostic indicators, the detection of plasma FBG and p53 protein in tumor tissue may contribute to increase the prognostic information in breast cancer.

Objective:To investigate the feasibility and safety of laparoscopic radical resection of hilar cholangiocarcinoma at multiple centers in China.Methods:Between December 2015 and August 2019, the clinical data of 143 patients who underwent LRHC in Affiliated Hospital of North Sichuan Medical College, Second Hospital of Hebei Medical University, Affiliated Hospital of Xuzhou Medical University, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Hunan Provincial People′s Hospital, the First Hospital Affiliated to Army Medical University, Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University, West China Hospital of Sichuan University, Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Chongqing Medical University were collected prospectively. There were 92 males and 51 females with age of (64±11) years (range: 53 to 72 years). Bismuth type: type I, 38 cases (26.6%), type Ⅱ, 19 cases (13.3%), type Ⅲa, 15 cases (10.5%), type Ⅲb, 28 cases (19.6%) and type Ⅳ, 43 cases (30.0%). The patients within the first 10 operation cases in each operation time (the first 10 patients in each operation team) were divided into group A (77 cases), and the patients after 10 cases in each operation time were classified as group B (66 cases); the cases with more than 10 cases in the center were further divided into group A 1 (116 cases), and the center with less than 10 cases was set as group A 2 (27 cases). T test or Wilcoxon test was used to compare the measurement data between groups, and the chi square test or Fisher exact probability method was used to compare the counting data between groups. Kaplan Meier curve was used for survival analysis. Results:All patients successfully completed laparoscopic procedure. The mean operation time was (421.3±153.4) minutes (range: 159 to 770 minutes), and the intraoperative blood loss was 100 to 1 500 ml (median was 300 ml) .Recent post-operative complications contained bile leakage, abdominal bleeding, abdominal infection, gastrointestinal bleeding, and delay gastric emptying, pulmonary infection, liver failure, et al.The post-operative hospital stay was (15.9±9.2) days. The operation time in group B was relatively reduced ( (429.5±190.7)minutes vs. (492.3±173.1)minutes, t=2.063, P=0.041) and the blood loss (465 ml vs. 200 ml) was also reduced ( Z=2.021, P=0.043) than that in group B. The incidence of postoperative biliary fistula and lung infection in patients in group A was significantly higher than that in group B (χ 2=4.341, 0.007; P=0.037, 0.047) .Compared with group A 2, the operation time in group A 1 was relatively reduced( (416.3±176.5)minutes vs. (498.1±190.4)minutes, t=2.136, P=0.034) , the incidence of bile leakage and abdominal cavity infection in group A 1 was lower than that in group A 2 (χ 2=7.537, 3.162; P=0.006, 0.046) . Kaplan Meier survival curve showed that the difference of short-term survival time between group A and group B was statistically significant ( P<0.05) . Conclusions:The completion of laparoscopic hilar cholangiocarcinoma radical surgery is based on improved surgical skills, and proficiency in standardized operation procedures.It is feasible for laparoscopic radical resection of hilar cholangiocarcinoma to well experienced surgeon with cases be strictly screened, but it is not recommended for widespread promotion at this exploratory stage.

Objective:To investigate the feasibility and safety of laparoscopic radical resection of hilar cholangiocarcinoma at multiple centers in China.Methods:Between December 2015 and August 2019, the clinical data of 143 patients who underwent LRHC in Affiliated Hospital of North Sichuan Medical College, Second Hospital of Hebei Medical University, Affiliated Hospital of Xuzhou Medical University, Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Hunan Provincial People′s Hospital, the First Hospital Affiliated to Army Medical University, Sir Run Run Shaw Hospital Affiliated to Medical College of Zhejiang University, West China Hospital of Sichuan University, Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Chongqing Medical University were collected prospectively. There were 92 males and 51 females with age of (64±11) years (range: 53 to 72 years). Bismuth type: type I, 38 cases (26.6%), type Ⅱ, 19 cases (13.3%), type Ⅲa, 15 cases (10.5%), type Ⅲb, 28 cases (19.6%) and type Ⅳ, 43 cases (30.0%). The patients within the first 10 operation cases in each operation time (the first 10 patients in each operation team) were divided into group A (77 cases), and the patients after 10 cases in each operation time were classified as group B (66 cases); the cases with more than 10 cases in the center were further divided into group A 1 (116 cases), and the center with less than 10 cases was set as group A 2 (27 cases). T test or Wilcoxon test was used to compare the measurement data between groups, and the chi square test or Fisher exact probability method was used to compare the counting data between groups. Kaplan Meier curve was used for survival analysis. Results:All patients successfully completed laparoscopic procedure. The mean operation time was (421.3±153.4) minutes (range: 159 to 770 minutes), and the intraoperative blood loss was 100 to 1 500 ml (median was 300 ml) .Recent post-operative complications contained bile leakage, abdominal bleeding, abdominal infection, gastrointestinal bleeding, and delay gastric emptying, pulmonary infection, liver failure, et al.The post-operative hospital stay was (15.9±9.2) days. The operation time in group B was relatively reduced ( (429.5±190.7)minutes vs. (492.3±173.1)minutes, t=2.063, P=0.041) and the blood loss (465 ml vs. 200 ml) was also reduced ( Z=2.021, P=0.043) than that in group B. The incidence of postoperative biliary fistula and lung infection in patients in group A was significantly higher than that in group B (χ 2=4.341, 0.007; P=0.037, 0.047) .Compared with group A 2, the operation time in group A 1 was relatively reduced( (416.3±176.5)minutes vs. (498.1±190.4)minutes, t=2.136, P=0.034) , the incidence of bile leakage and abdominal cavity infection in group A 1 was lower than that in group A 2 (χ 2=7.537, 3.162; P=0.006, 0.046) . Kaplan Meier survival curve showed that the difference of short-term survival time between group A and group B was statistically significant ( P<0.05) . Conclusions:The completion of laparoscopic hilar cholangiocarcinoma radical surgery is based on improved surgical skills, and proficiency in standardized operation procedures.It is feasible for laparoscopic radical resection of hilar cholangiocarcinoma to well experienced surgeon with cases be strictly screened, but it is not recommended for widespread promotion at this exploratory stage.

Objective To investigate the effect of terlipressin on hepatic and renal function in cirrhotic patients undergoing hepatectomy.Methods Aanlyze the clinical data of 57 patients following irregular hepatectomy for hepatocellular carcinoma with cirrhosis,according to whether use terlipressin or not after operation,which were divided into terlipressin group (A group,n =27) and control group (B group,n =30).Liver function parameters (ALT,AST,TB),ascites,urine volume and renal function parameters (Cr,BUN) preoperatively and on postoperative day(POD) 1,3,5 and 7 were compared between the two gruops.Results Compared with those of POD 1,the levels of ALT,AST and ascites on POD 3,5,7 were significantly lower in two groups (P ＜ 0.05),urine volume was significantly increased (P ＜ 0.05),Cr of POD 7 was significantly lower (P ＜0.05),but it is more remarkable in group A than group B.The levels of ALT in terlipressin group on POD 5,7 were (144.9 ±76.3) U/L,(100.5 ±61.5) U/L,which were lower than those of (267.2±91.2) U/L,(199.3 ±70.5) U/L in control group.On POD 3,5,7,the levels of AST,BUN,Cr and peritoneal fluid in terlipressin group,which were respectively(211.1 ±99.8) U/L,(80.4 ±54.6) U/L,(50.6 ±46.5) U/L,(6.6 ± 1.9) mmol/L,(6.5 ± 1.7) mmol/L,(6.3 ± 2.1) mmol/L,(74.3 ± 10.9) μmol/L,(71.5 ± 8.9) μmol/L,(58.7 ±4.1) μmol/L,(247.6±60.3) ml,(58.8±54.3) ml,(40.2±31.8) ml,were significantly lower than those in control group which were (298.7 ±131.2) U/L,(201.1 ±93.4) U/L,(114.7 ±70.3) U/L,(7.3 ± 1.9) mmol/L,(7.2±1.8) mmol/L,(7.1±1.7) mmol/L,(79.5±15.1) μmol/L,(76.9±16.2) μmol/L,(69.4±11.4) μmol/L,(275.2±88.1) ml,(191.7±71.6) ml,(93.2±50.2) ml.while urine volume of (2232.3±409.8) ml,(2270.5 ±395.8) ml,(2179.0±301.4) ml was much more than that of (1921 ± 510.4) ml,(2019.1 ±411.2) ml,(1978.7±323.7) ml in the control group,the differences in the two groups were statistically significant (P ＜ 0.05).There were 11 (36.7％) patients with hepatic and renal dysfunction and hepatorenal syndrome after operation in group B,while only 2 (7.4％) patients in group A.Conclusions The use of terlipressin after partial liver resection has a protective effect on hepatic and renal function in patients with cirrhosis,and can reduce postoperative ascites and prevent hepatorenal syndrome.

Objective To evaluate the efficiency and influencing factors of ultrasound-guided percutaneous radiofrequency ablation (RFA) as treatment of hepatic malignant tumors.Methods Clinical data and follow-up radiographic images of patients with hepatic malignant tumors who had undergone treatment with ultrasound-guided percutaneous RFA at our hospital between March 2012 and March 2014 were reviewed.Rates of incomplete ablation,recurrence,and tumor progression were calculated,and the factors affecting each were analyzed.Results Four hundred and twelve lesions were ablated in a total of 392 ultrasound-guided percutaneous RFA procedures applied to 360 patients.The average tumor size was 2.51±1.10 cm.During at least 3 months of follow-up,the complete ablation rate was 86.11％ (310/360),the recurrence rate was 7.78％ (28/360),and the progression rate was 6.1％ (22/360).Tumors with vessel-proximal location,size of ≥ 3 cm and ≥ 3 month presence had significantly higher rates of residual lesions after ablation (x2 =4.431,10.889 and 8.000,respectively;p＜0.05).Tumors with ≥ 3 month presence had significantly higher rates of recurrence and progression (x2 =29.032 and 22.092,P ＜ 0.05).Conclusion Ultrasound-guided percutaneous RFA can effectively control local progression of hepatic malignant tumors.Tumor size,length of presence,and vesselproximal location are influencing factors of complete ablation rate,while length of presence is also an influencing factor for the recurrence and progression rates.

The dissolution of nickel from nitinol alloy under different extraction conditions was investigated when biological tests of nitinol medical devices were carried out. It discussed the equivalence of these extraction conditions and found the best extraction conditions. In the experiment, two brands of nitinol were chosen and extracted under different extraction conditions according to GB/T 16886-12. Plasma emission spectrometer was used to analyse the concentration of nickel in extract liquid. The results show that there is no equivalence among these extraction conditions for nitinol materials. And it is suggested that (37 +/- 1) degree C, (72 +/- 2) h could be used as normal extraction condition and (70 +/- 2) degrees C, (24 +/- 2) h as accelerated extraction condition.
Alloys ; chemistry ; Biocompatible Materials ; Materials Testing ; Nickel ; chemistry ; Temperature ; Titanium