BACKGROUND:Early exercise treatment is the main prevention way for traumatic joint contracture and is also a research focus.Swimming may be a potential intervention for joint contracture due to the special physical properties of water. OBJECTIVE:To explore the effects of swimming on the development of joint contracture in a rat model and study its mechanisms. METHODS:Twenty-four Sprague-Dawley rats were randomly divided into a blank control group(n=8)and a joint contracture group(n=16).After the surgical operation of knee joint contracture rat models,the joint contracture group was randomly subdivided into a surgical control group(n=8)and a swimming treatment group(n=8).Swimming started in the swimming treatment group in the second week after surgery and lasted for a total of 5 weeks.At the 6th week after surgery,the body mass,knee joint range of motion,and quadriceps diameter were tested,and the diameter/body mass index was calculated.Hematoxylin-eosin staining was performed to detect the pathological changes in the knee joint capsule and quadriceps muscle,and Masson staining was used to observe fibrotic changes in the knee joint capsule.Furthermore,the protein expression of transforming growth factor β1 and type I collagen in the knee joint capsule was quantified by immunohistochemical assay and western blot was performed to detect the protein expression of MuRF1 in the quadriceps femoris. RESULTS AND CONCLUSION:Compared with the blank control group,the knee range of motion decreased in the surgical control and swimming treatment groups(P<0.01),and knee extension deficit and arthrogenic extension deficit were significantly increased(P<0.01),the diameter of the quadriceps muscle was decreased(P<0.01),the joint capsule showed significant fibrosis,the quadriceps muscle was atrophied,and the diameter/body mass index was decreased(P<0.01).Compared with the surgical control group,the swimming treatment group showed a significant increase in knee joint range of motion and quadriceps diameter(P<0.01),and significant improvement in joint capsule fibrosis and quadriceps atrophy.Compared with the blank control group,collagen fiber content and expression of transforming growth factor β1 and type I collagen were increased in the joint capsule of rats in both the surgical control group and the swimming treatment group(P<0.01).Compared with the surgical control group,collagen fiber content and expression of transforming growth factor β1 and type I collagen protein in the joint capsule were decreased in the swimming treatment group.Compared with the blank control group,the expression of MuRF1 protein in the quadriceps muscle of rats in the surgical control group and the swimming treatment group was increased(P<0.05).Compared with the surgical control group,the expression of MuRF1 protein in the quadriceps muscle of rats in the swimming treatment group was decreased(P<0.05).To conclude,early swimming intervention reduces transforming growth factor β1 and type I collagen expression in the joint capsule of traumatic joint contracture rats,decreases MuRF1 expression in the quadriceps muscle,and increases joint range of motion and quadriceps diameter,thereby inhibiting the development of joint contracture.

Objective:To investigate the efficacy and mechanism of static progressive stretch (SPS) with different parameters in the treatment of stiff knee in rats.Methods:Fifty-six male 8-week SD rats were randomly divided into an operation group ( n=48) and a blank group ( n=8, normal feeding rats without any treatment). The knee joints of the rats in the operation group were fixed with Kirschner wire for 4 weeks to create models of right knee flexion stiffness. The 42 rats with successful modeling were randomly divided into 6 groups ( n=7): the model group was executed and sampled after successful modeling, the spontaneous recovery group was not given any treatment after successful modeling, group T1 was given SPS treatment for 20 min once per day, group T2 was given SPS treatment for 30 min once per day, group T3 was given SPS treatment for 20 min once every 2 days, and group T4 was given SPS treatment for 30 min once every 2 days. After 16 days, the range of knee motion, number of myofibroblasts, and positive proportion of transforming growth factor- β1 (TGF- β1) in the joint capsule were detected and compared between groups. Results:The ranges of knee motion in the spontaneous recovery group and the 4 SPS treatment groups were significantly greater than those before treatment ( P<0.05), and the improvements in the range of knee motion in the 4 SPS treatment groups were significantly greater than that in the spontaneous recovery group ( P<0.05). The range of knee motion in group T2 (112.29°±1.89°) was improved the most significantly. The number of myofibroblasts was (23.72±10.75)/HP, which was significantly smaller than that in T3 group [(55.72±33.56)/HP] or in T4 group [(50.72±33.34)/HP] ( P<0.05). The positive proportions of TGF- β1 in the joint capsule in the 4 SPS treatment groups were significantly lower than that in the model group, and the positive proportion of TGF- β1 in the joint capsule in group T2 (0.51%±0.38%) was significantly lower than those in group T3 and T4 ( P<0.05). Conclusions:As SPS treatment can reduce the expression of TGF- β1 in the joint and inhibit the excessive proliferation of myofibroblasts to alleviate the pathological changes in a stiff knee, it has a significant effect on the stiff knee in rats. The SPS treatment for 30 minutes and once per day may lead to the best efficacy.

The Wnt signaling pathway plays an important role in maintaining liver homeostasis and liver regeneration.In healthy livers,the Wnt signaling pathway is mostly inactive,but it is continuously overactivated during cell renewal or regeneration processes,as well as in certain pathological conditions,diseases,precancerous states,and cancers.Persistent liver cell injury often leads to chronic liver diseases such as liver fibrosis,liver cirrhosis,and liver cancer.This article summarizes the basic structural features of the Wnt signaling pathway and analyzes its important role in the pathological progression of various liver diseases,so as to provide new ideas for the prevention and treatment of liver diseases in clinical practice.

Background and purpose:Radical surgery after neoadjuvant immunotherapy combined with chemotherapy(nICT)in patients with locally advanced esophageal squamous cell carcinoma(LAESCC)has good efficacy and safety,and it can improve the patients'pathological complete remission(pCR)rate,main pathologic response(MPR)rate and R0 resection rate.The prognosis of patients with pCR/MPR after nICT is significantly better compared with patients without pCR.The prognosis of patients achieving pCR/MPR after neoadjuvant therapy has been demonstrated to be significantly better than that of patients with non-pCR/MPR.Therefore,finding predictive factors of pCR/MPR is beneficial for us to screen out the advantageous populations for combination therapy.The aim of this study was to investigate the value of clinical data of patients with LAESCC before and after nICT in predicting the degree of remission of different pathologies after radical surgery following neoadjuvant treatment and to observe the safety of the treatment.Methods:Data of patients with locally LAESCC who underwent radical surgery after nICT from January 2019 to June 2023 at the Affiliated Hospital of Chuanbei Medical College were collected.The clinical data of all patients as well as some blood,inflammation and nutritional indexes of patients before and after neoadjuvant therapy were collected,and the patients were grouped according to the different degrees of pathological remission after neoadjuvant therapy.Data were analyzed by multi-group comparative analysis of variance(ANOVA)and LSD-t post-hoc test.We explored the factors that had an influence on the different degrees of pathological remission,and collected and recorded the patients'adverse reactions during neoadjuvant therapy as well as their eventual surgeries.Results:Data of 62 patients with LAESCC treated with nICT who underwent radical surgery were collected.Only one patient showed grade 4 myelosuppression during neoadjuvant therapy,and the rest of the patients had adverse reactions≤grade 2.The R0 resection rate of the surgery was 98.39%.The present study was compared with the previous studies of LAESCC treated with neoadjuvant chemotherapy followed by radical surgery performed in Affiliated Hospital of Chuanbei Medical College.Compared with the previous studies conducted in our center,no significant difference was observed in terms of operation time,intraoperative bleeding,postoperative hospitalization time and surgical complications.The postoperative pathologic results showed that the pCR rate was 22.58%(14/62),and the MPR rate was 40.32%(25/62).According to the different tumor regression grade(TRG)after surgery,patients were divided into 3 groups of TRG1,TRG2 and TRG3-4,and differences in the platelet distribution width(PDW)before neoadjuvant therapy and the preoperative neutrophil-to-lymphocyte ratio(NLR)after neoadjuvant therapy were statistically significant among the 3 groups(P＜0.05).Further intra-group two-by-two comparisons of PDW before neoadjuvant therapy and NLR before surgery after neoadjuvant therapy were performed for the three groups of patients,respectively,and it was found that the PDW and NLR in the TRG2 group were lower compared with the TRG3-4 group,and the differences were statistically significant(P＜0.05).Conclusion:Radical surgery after nICT treatment in patients with LAESCC can have high R0 resection rate,pCR rate,MPR rate and reliable safety,and the lower PDW of patients before neoadjuvant therapy and the lower NLR of patients before surgery after neoadjuvant therapy predict better pathological remission efficacy.

Objective:To explore the effectiveness of body weight support in gait training after surgery for an ankle fracture.Methods:Thirty-eight ankle fracture patients who received surgery were divided at random into an observation group and a control group, each of 19. In addition to 3 sessions of routine gait rehabilitation training a week for 6 weeks, only those in the observation group received body weight support training with body weight support boots. Gait data were collected using the GaitWatch three-dimensional gait action capture and training system before the training and after 2, 4 and 6 weeks of the training.Results:At each assessment the gait frequency, gait cycle, stride length, stride rate, bilateral step length, step length deviation, bilateral support phase and bilateral swing phase of both groups had improved significantly. After 6 weeks the average stride frequency, gait cycle, stride length on both sides and speed of the observation group had improved significantly more than among the control group. Step length deviation was not significantly different, however. At each evaluation the proportions of affected and healthy side support had decreased significantly in both groups, but affected and healthy side swing had increased and the proportion of bilateral support had decreased significantly.Conclusion:Body weight support training with body weight support boots can significantly improve gait after ankle fracture surgery. Its effect is superior to that of conventional gait training.

Objective:To investigate the knowledge and practice of the Sixth Chinese national consensus report on the management of Helicobacter pylori ( H. pylori) infection (treament excluded) (referred to as sixth national consensus)and 2022 Chinese national clinical practice guideline on H. pylori eradication treatment (referred to as guideline) among gastroenterologists in China, so as to provide out relevant training in the future. Methods:A questionnaire was designed according to sixth national consensus and guideline, including knowledge and practice of sixth national consensus and guideline, and the detection, indications of eradication, the relationship between infection and gastrointestinal microbiota, and eradication of H. pylori. From November 1 to 30 in 2023, the questionnaire-based survey was conducted among 1 506 gastroenterologists from secondary and tertiary hospitals of 24 provinces, autonomous regions and municipalities in China with convenience sampling method using the "Questionnaire Star" online questionnaire platform and the questionnaire link was sent by WeChat. Descriptive methods were used for statistical analysis. Results:A total of 1 442 valid questionnaires were collected. The awareness rate of sixth national consensus and guideline of gastroenterologists was 83.7% (1 207/1 442), and 47.2% (680/1 442) had read the relevant content in detail. Urea breath test (97.4%, 1 404/1 442) was the most commonly used method for diagnosing current H. pylori infection, however, more than half of the physicians chose serological test (53.3%, 769/1 442) for the diagnosis of current infection. The common indications of H. pylori eradication could be identified by 84.3%(1 215/1 442) of gastroenterologists. The most well-known eradication regimen was bismuth quadruple regimen (98.5%, 1 421/1 442), while some physicians still believed that the standard triple regimen (31.8%, 459/1 442) and sequential regimen (21.9%, 316/1 442) were recommended by the guideline. A further 20.2% (291/1 442) frequently prescribed a triple regimen combined with gastric mucosal protectants and the awareness rate of high-dose dual regimen was 59.1% (852/1 442). Amoxicillin + clarithromycin (65.4%, 943/1 442) and amoxicillin+ furazolidone (20.1%, 290/1 442) were commonly used antibiotic combinations in bismuth quadruple therapy. Potassium-competitive acid blockers and double-dose proton pump inhibitors were commonly used in bismuth quadruple therapy by 45.4% (655/1 442) and 46.0% (664/1 442) of physicians, respectively. For patients with multiple failed eradications, furazolidone was the most commonly used antibiotic for re-eradication(71.7%, 1 034/1 442). Conclusion:The knowledge and practice of gastroenterologists on H. pylori infection in China deviates from the new consensus and guideline, and more publicity and training should be carried out in future to improve the ability of gastroenterologists to standardise the diagnosis and treatment of H. pylori infection.

Objective To investigate the ability of combined baseline serum markers, i.e., HBV DNA, HBV RNA, HBsAg, and HBcrAg, to predict HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) treated by nucleos(t)ide analogues. Methods A retrospective analysis was performed for 83 HBeAg-positive patients selected as subjects from the prospective CHB follow-up cohort established by Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, from June 2007 to July 2008, and the baseline serum levels of HBV DNA, HBV RNA, HBsAg, and HBcrAg were analyzed. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman method was used for correlation analysis. A Cox regression model was established to calculate HBeAg seroconversion prediction score, and the time-dependent receiver operating characteristic curve was used to evaluate the ability of combined markers in predicting HBeAg seroconversion. The Kaplan-Meier method was used to calculate cumulative seroconversion rate in each group, and the Log-rank test was used for comparison between groups. Results For the 83 HBeAg-positive patients, the median follow-up time was 108 months, and 44.58%(37/83) of these patients achieved HBeAg seroconversion. Compared with the non-seroconversion group, the HBeAg seroconversion group had significantly lower baseline serum levels of HBV DNA [6.23(1.99-9.28) log 10 IU/mL vs 7.69(2.05-8.96) log 10 IU/mL, Z =-2.345, P =0.019] and HBV RNA [4.81(1.40-7.53) log 10 copies/mL vs 6.22(2.00-8.49) log 10 copies/mL, Z =-1.702, P =0.010], and there were no significant differences in the levels of HBsAg and HBcrAg between the two groups ( P > 0.05). The Cox regression equation constructed based on the above serum markers showed a median score of 0.95(range 0.37-3.45) for predicting HBeAg seroconversion. In the total population, the combined score was negatively correlated with HBsAg, HBV DNA, HBV RNA, and HBcrAg ( r =-0.697, -0.787, -0.990, and -0.819, all P < 0.001). Based on the median prediction score, the patients were divided into high HBeAg seroconversion group and low HBeAg seroconversion group; as for the prediction of HBeAg seroconversion rate at 36, 60, and 84 months, the high HBeAg seroconversion group had a seroconversion rate of 43.90%, 51.20%, and 63.10%, respectively, while the low HBeAg seroconversion group had a seroconversion rate of 9.60%, 17.00%, and 19.8%, respectively, and there was a significant difference between the two groups ( χ 2 =11.6, P < 0.001). Conclusion The combined prediction score based on baseline serum HBV markers can predict HBeAg seroconversion in CHB patients treated by nucleos(t)ide analogues.

Objective:To investigate the value of spectral CT based iodine concentration (IC) parameters for preoperative prediction of lymphovascular invasion (LVI) in gastric cancer.Methods:Between January 2021 and November 2021, 266 patients diagnosed as gastric adenocarcinomas by endoscopy and undergoing gastrectomy at the Affiliated Cancer Hospital of Zhengzhou University were recruited prospectively. They were divided into LVI and non-LVI groups according to pathological reports. Triple phase contrasted enhanced CT scans, including arterial phase (AP), venous phase (VP) and delayed phase (DP) were performed on a spectral CT platform within one week before surgery. The IC of gastric cancer lesions at three enhanced phases were measured based on iodine maps, and the normalized IC (nIC) was calculated. The thickness of the tumor was measured. Clinicopathological features were collected, including ulceration, pathological tumor staging (pT), pathological node staging (pN), histodifferentiation, Lauren subtype, perineural invasion (PNI), positive node numbers and positive node ratio. Student′s t tes t or Mann-Whitney U test were used to compare the differences of continuous variables between the two groups, while Chi-square test or Fisher′s exact test was used for categorical data. Multivariable logistic regression analysis was used to screen independent risk factors of LVI, and to build a combined parameter based on risk factors. The receiver operating characteristic curve analysis was performed to determine the predictive efficacy of IC parameters and the combined parameter for LVI. DeLong′s test was used to compare the differences among different area under the curve (AUC). Results:There were statistical differences in tumor thickness, ulceration, pT, pN, histodifferentiation, positive node numbers, positive node ratio, Lauren subtype and PNI between LVI and non-LVI groups ( P<0.05). The values of IC VP, IC DP, nIC VP, nIC DP in LVI group were statistically higher than those in non-LVI group ( t=3.77, 4.23, 4.25, 6.12, all P<0.001), with the AUC (95%CI) of 0.674 (0.610-0.738), 0.677 (0.614-0.741), 0.731 (0.671-0.792), 0.700 (0.636-0.764) for predicting LVI, respectively. Multivariable logistic regression analysis revealed that tumor thickness (OR=1.148, 95%CI 1.085-1.237, P<0.001) and nIC VP (OR=209.904, 95%CI 14.874-644.362, P<0.001) were independent predictors for LVI, the combined parameter incorporating these two factors yielded an AUC (95%CI) of 0.790 (0.736-0.937), which was statistically higher than any single parameter of IC VP, IC DP, nIC VP and nIC DP ( Z=3.07, 3.29, 2.10, 2.60, P=0.002, 0.001, 0.036, 0.009). Conclusion:The IC and nIC values of gastric cancer lesions derived from the VP and DP on spectral CT can effectively predict LVI status in gastric adenocarcinomas, and the combination of nIC VP and tumor thickness can further improve the predictive efficacy.

Objective To investigate the consistency between Shengxiang (S) and Xinbo (X) real-time PCR methods in the quantification of HBV RNA. Methods In the prospective follow-up cohort of 108 chronic hepatitis B (CHB) patients established from July 2007 to August 2008, 20 patients with HBeAg seroconversion were selected, and 20 patients without seroconversion were selected by propensity score matching at a ratio of 1∶ 1. The two quantification methods from S and X companies were used, and a retrospective analysis was performed for HBV RNA in serum samples at baseline and weeks 12, 24, and 48. The paired t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data. The Pearson correlation coefficient, intraclass correlation coefficient (ICC), and the Bland-Altman method were used to evaluate the consistency of the two quantification methods. Results A total of 132 serum samples were tested by S reagent, and 154 were tested by X reagent; the detection rate of HBV RNA was 100% by both reagents. A total of 131 serum samples were tested by both reagents, with 34 samples at baseline and 29, 35, and 33 samples, respectively, at weeks 12, 24, and 48 of follow-up; at these four time points, the HBV RNA quantification data detected by X reagent were significantly higher than those detected by S reagent (5.75±1.64/5.43±1.73/5.13±1.54/4.76±1.55 log 10 copies/mL vs 4.80±1.48/4.52±1.53/4.10±1.50/3.92± 1.43 log 10 copies/mL, t =8.348, t =5.341, Z =-5.086, Z =-4.762, all P < 0.001). The correlation analysis of the two methods showed a Pearson correlation coefficient of 0.915 (95% confidence interval [ CI ]: 0.836-0.957) and an ICC of 0.771(95% CI : -0.021 to 0.931) at baseline, a Pearson correlation coefficient of 0.849(95% CI : 0.701-0.927) and an ICC of 0.733(95% CI : 0.138-0.902) at week 12, a Pearson correlation coefficient of 0.951(95% CI : 0.905-0.975) and an ICC of 0.776(95% CI : -0.058 to 0.942) at week 24, and a Pearson correlation coefficient of 0.933(95% CI : 0.867-0.967) and an ICC of 0.804(95% CI : -0.014 to 0.944) at week 48 (all P < 0.05). The Bland-Altman analysis showed that the difference of 96.18%(126/131) samples tested by the two methods was within the mean difference±1.96 standard deviation. Conclusion HBV RNA quantification by X reagent is higher than that by S reagent, while the two real-time PCR quantification methods show a good consistency in CHB patients with HBeAg seroconversion and those without seroconversion.

Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.