Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective To observe the effects of grain-sized moxibustion on Th1 cell/Th2 cell(Th1/Th2)balance and transcription factors T-box transcription factor(T-bet)and GATA binding protein 3(GATA3)in immunosuppressive mice induced by chemotherapy.Methods According to the random number table method,32 SPF male CD-1(ICR)mice were randomly divided into the normal group,model group,levamisole hydrochloride group,and grain-sized moxibustion group,with eight mice per group.Except for the normal group,the immunosuppressive model was established by intraperitoneal injection of cyclophosphamide(80 mg/kg,once daily for three consecutive days).Mice in the levamisole hydrochloride group were given levamisole hydrochloride solution(10 mg/kg)by gavage.Mice in the grain-sized moxibustion group was given grain-sized moxibustion at"Guanyuan"(CV4),bilateral"Zusanli"(ST36),and bilateral"Sanyinjiao"(SP6),with three Zhuang at each acupoint for approximately 30 s each.The intervention was administered once daily for seven consecutive days.The general condition of mice was observed.The spleen mass and spleen index were detected.The pathological changes of spleen tissue were observed by HE staining.The protein and mRNA expressions of T-bet,GATA3,interferon-γ(IFN-γ),and interleukin(IL)-4 in spleen tissue of mice were detected by Western blotting and real-time PCR.The contents of IFN-γ,IL-2,and IL-4 in serum of mice were detected by enzyme-linked immunosorbent assay.Results Compared with the normal group,the mice in the model group were slow in response,unstable in gait;the spleen weight and spleen index were increased(P<0.05);the structure of spleen tissue was disordered,the mRNA and protein expressions of T-bet and IFN-γ in spleen tissue were decreased,and the mRNA and protein expressions of GATA3 and IL-4 were increased(P<0.05);the contents of IFN-γ and IL-2 in serum were decreased,and the content of IL-4 was increased(P<0.05).Compared with the model group,the general condition of mice in the levamisole hydrochloride group and the grain-sized moxibustion group was improved,the structure of spleen tissue was improved,the mRNA and protein expressions of T-bet and IFN-γ in spleen tissue were decreased,and the mRNA and protein expressions of GATA3 and IL-4 were increased(P<0.05);the contents of IFN-γ and IL-2 in serum were decreased,and the content of IL-4 was increased(P<0.05).Conclusion Grain-sized moxibustion can significantly improve the immunosuppressive symptoms induced by chemotherapy.The mechanism may be through regulating the expressions of transcription factors T-bet and GATA3,regulating Th1/Th2 balance,and thus restoring the immune balance.

Objective To compare the clinical outcomes of using elastic intramedullary nail and plate to fix fibular frac-ture.Methods The 60 patients with tibiofibular fractures admitted from January 2015 to December 2022 were divided into two groups:intramedullary nail group and plate group,30 cases each,intramedullary nail group was treated with elastic in-tramedullary nail fixation group,plate group was treated with steel plate and screw fixation group.Intramedullary nail group,there were 18 males and 12 females,aged from 22 to 75 years old with an average of(39.4±9.8)years old,including 24 cases of traffic accidents injury,6 cases of falling injury,23 cases of closed fractures,7 cases of open fractures.Steel plate group,there were 15 males and 15 females,aged from 24 to 78 years old with an average of(38.6±10.2)years old.The 22 cases were injured by traffic accident,8 cases were injured by falling.The 24 cases were closed fractures and 6 cases were open fractures.The operation time,intraoperative bleeding,American Orthopedic Foot and Ankle Society(AOFAS)ankle and hind foot scores,clinical healing time of fibula and the incidence of wound complications were compared between the two groups.Re-sults The patients in both groups were followed up for 6 to 21 months,with an average of(14.0±2.8)months.Compared with plate group,intramedullary nail group had shorter operative time,less bleeding,shorter clinical healing time of fibula,and low-er infection rate of incision,and the difference was statistically significant(P＜0.05).There were 2 cases of delayed healing in intramedullary nail group,1 case of nonunion in plate group,and 2 cases of delayed healing in plate group,and there was no statistically significant difference between the two groups(P＞0.05).In the last follow-up,according to the AOFAS scoring standard,the ankle function in intramedullary nail group was excellent in 17 cases,good in 12 cases,fair in 1 case,with an av-erage of(88.33±4.57)points,while in plate group,excellent in 16 cases,good in 10 cases,fair in 4 cases,with an average of(87.00±4.14)points;There was no statistical difference between the two groups(P＞0.05).Conclusion Elastic intramedullary nail has the advantages of short operation time,less intraoperative bleeding,short fracture healing time and less incision com-plications in the treatment of fibular fracture,which is worthy of clinical application.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To explore the application value of biplane transrectal ultrasound (TRUS) combining superb microvascular imaging (SMI) in evaluating preoperative T stage of mid-low rectal cancer.Methods:From Jan 2021 to Apr 2022, 90 patients with middle and low rectal cancer undergoing surgical treatment in Da Ping Hospital, Army Medical Center of PLA were equally divided into trial group and control group . Patients in the control group received TRUS combining with color Doppler blood flow imaging (CDFI) mode, patients in the trial group received additional SMI . Preoperative ultrasound T staging was performed. Artery blood flow resistance index (RI), pulsation index (PI), peak systolic velocity (PSV), and end diastolic velocity (EDV) of tumors were measured and recorded. Receiver operating characteristics curves were drawn to evaluate the diagnostic efficacy.Results:The accuracy rate of the control group was 67% (30/45), and the consistence with the pathological stage (Kappa=0.510, P<0.05) was lower than that of 84% (38/45) and (Kappa=0.779, P<0.001) of the trial group ( χ2=3.850, P<0.05). Among different T stages, the difference of RI and PI were significant ( F=5.619, P=0.002; F=25.500, P<0.001), the difference of PSV was not significant ( F=1.464, P=0.231), and the difference of EDV was weakly correlated ( F=2.723, P=0.05). The ROC curves showed that the area under curve of RI, PI, EDV, and PSV was 0.573, 0.517, 0.527 and 0.501, respectively. With the diagnostic sensitivity rate for T1 to T4 as 70.4%, 58.8%, 93.3%, 68.8%, while the diagnostic specificity rate was 87.3%, 90.4%, 96.8%, 93.2%. Conclusion:Biplane TRUS combining SMI can improve the accuracy in preoperative ultrasound T staging of mid-low rectal cancer.

Abstract：Objective To optimize the production process of inactivated vaccine of Aeromonas veronii（AV）CA07 strain. Methods The fermentation culture process of AV CA07 strain liquid was determined through the optimization of the culture time（2～16 h），medium（optimized fermentation medium，LB medium and NB medium）and fermentation conditions（in⁃ oculation amount of 1%，5%，10% and 15%；ventilation rate of 2，4，6 and 8 L／min and fermentation time of 6，8，10 and 12 h）. The optimal inactivation process was determined through the comparison of the final concentration of formalde⁃ hyde solution（0. 10%，0. 20%，0. 30% and 0. 40%），inactivation temperature（28 and 37 ℃）and inactivation time（24， 48 and 72 h）. The large⁃scale production process of inactivated vaccine of AV CA07 strain in 500 L fermentor was estab⁃ lished and the prepared vaccines were tested for safety and immunogenicity. Results The optimal inoculation amount of AV CA07 strain was 5%，ventilation rate was 4 L／min and culture time was 10 ~ 12 h. The optimal inactivation condition was adding formaldehyde solution with final concentration of 0. 30% incubating at 37 ℃ for 24 h. The number of viable bacteria in the fermentation broth of AV CA07 strain prepared in 500 L fermentor was more than 8 × 109 CFU／mL. All crucian carps immunized with the inactivated vaccine by abdomen survived. After challenge，the relative immune protection rate was more than 90%. Conclusion AV CA07 strain inactivated vaccine prepared by optimized production process showed good safety and immunogenicity.

OBJECTIVE: To investigate the high risk factors of failure of autologous arteriovenous fistula (AVF) in hemodialysis patients. METHODS: A retrospective study was conducted, patients with maintenance hemodialysis (MHD) undergoing AVF admitted to General Hospital of Western Theater Command from January 2021 to December 2022 were enrolled, including 107 patients with normal AVF and 168 patients with AVF dysfanction. According to the causes of AVF failure, the patients were divided into AVF stenosis group (n = 103) and AVF thrombosis group (n = 65). Age, gender, body mass index (BMI) and comorbidities (hypertension, diabetes, coronary heart disease) and other clinical data of all patients were collected. Hemoglobin, hematocrit, white blood cell count, neutrophil count, lymphocyte count, platelet count, C-reactive protein (CRP), high density lipoprotein, low density lipoprotein, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) within 1 month of AVF use in normal dialysis patients and 1 week before AVF failure. Multivariate Logistic regression was used to analyze the independent risk factors of AVF dysfuction in MHD patients. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of risk factors on AVF dysfuction in MHD patients. RESULTS: (1) There were significant differences in age, BMI, hypertension, hemoglobin, hematocrit, PLR and CRP [age (years): 56.94±14.32, 58.83±14.05, 51.57±13.19; BMI (kg/m²): 22.83±3.10, 21.27±4.98, 23.35±2.72; hypertension: 93.20%, 64.62%, 86.92%; hemoglobin (g/L): 110.82±22.16, 88.70±24.00, 87.95±23.45; hematocrit: 0.350±0.069, 0.282±0.076, 0.275±0.071; PLR: 197.35±113.59, 192.55±138.25, 162.12±73.25; CRP (mg/L): 10.01±4.02, 8.18±5.42, 3.17±1.30, all P < 0.05], among AVF stenosis group, AVF thrombosis group and AVF normal group, there were statistically significant differences no statistically significant difference was found in other indexes among three groups. (2) Multivariate Logistic regression analysis showed that hypertension [odds ratio (OR) = 4.849, 95% confidence interval (95%CI) was 1.278-18.397, P = 0.020], elevated CRP levels (OR = 2.104, 95%CI was 1.533-2.888, P = 0.000) were associated with AVF stenosis. Elevated CRP levels (OR = 1.984, 95%CI was 1.442-2.730, P = 0.000) was an independent risk factor for AVF thrombosis. Analysis of ROC curve showed that the area under the curve (AUC) of AVF dysfunction predicted by CRP was 0.712, 95%CI was 0.637-0.786, P = 0.000; CRP cut-off value was 1.8 mg/L, the sensitivity was 67.0%, the specificity was 83.7%. CONCLUSIONS Elevated CRP is an independent risk factor for AVF failure in hemodialysis patients, which can be used to predict the occurrence of AVF failure.
Humans ; Retrospective Studies ; Constriction, Pathologic ; Renal Dialysis/adverse effects* ; Lymphocytes ; C-Reactive Protein ; Risk Factors ; Hypertension ; Hemoglobins ; Thrombosis ; ROC Curve ; Prognosis

Objective: To examine the clinical effect of minimally invasive duodenum preserving pancreatic head resection(DPPHR) for benign and pre-malignant lesions of pancreatic head. Methods: The clinical data of patients with diagnosis of benign or pre-malignant pancreatic head tumor were retrospectively collected and analyzed,all of them underwent laparoscopic or robotic DPPHR between October 2015 and September 2021 at Division of Gastrointestinal and Pancreatic surgery,Zhejiang Provincial People's Hospital. Thirty-three patients were enrolled with 10 males and 23 females. The age(M(IQR)) was 54(32) years old(range: 11 to 77 years old) and the body mass index was 21.9(2.9)kg/m²(range: 18.1 to 30.1 kg/m²). The presenting symptoms included abdominal pain(n=12), Whipple triad(n=2), and asymptomatic(n=19). There were 7 patients with hypertension and 1 patient with diabetes mellitus. There were 19 patients who were diagnosed as American Society of Anesthesiologists class Ⅰ and 14 patients who were diagnosed as class Ⅱ. The student t test,U test, χ² test or Fisher exact test was used to compare continuous data or categorized data,respectively. All the perioperative data and metabolic morbidity were analyzed and experiences on minimally invasive DPPHR were concluded. Results: Fourteen patients underwent laparoscopic DPPHR,while the rest of 19 patients received robotic DPPHR. Indocyanine green fluorescence imaging was used in 19 patients to guide operation. Five patients were performed pancreatico-gastrostomy and the rest 28 patients underwent pancreaticojejunostomy. Pathological outcomes confirmed 9 solid pseudo-papillary neoplasms, 9 intraductal papillary mucinous neoplasms, 7 serous cystic neoplasms, 6 pancreatic neuroendocrine tumors, 1 mucous cystic neoplasm, 1 chronic pancreatitis. The operative time was (309.4±50.3) minutes(range:180 to 420 minutes),and the blood loss was (97.9±48.3)ml(range:20 to 200 ml). Eighteen patients suffered from postoperative complications,including 3 patients experienced severe complications(Clavien-Dindo Grade ≥Ⅲ). Pancreatic fistula occurred in 16 patients,including 8 patients with biochemical leak,7 patients with grade B pancreatic fistula and 1 patient with grade C pancreatic fistula. No one suffered from the duodenal necrosis and none perioperative death was occurred. The length of hospital stay was 14(7) days (range:6 to 87 days). The follow-up was 22.6(24.5)months(range:2 to 74 months). None suffered from recurrence or metastasis. During the follow-up,all the patients were free of refractory cholangitis. Moreover,in the term of endocrine dysfunction,no postoperative new onset of diabetes mellitus were observed in the long-term follow-up. However,in the view of exocrine insufficiency,pancreatic exocrine insufficiency and non-alcoholic fatty liver disease (NAFLD) was complicated in 2 and 1 patient,respectively,with the supplement of pancreatic enzyme,steatorrhea and weight loss relieved,but NAFLD was awaited to be seen. Conclusions: Minimally invasive DPPHR is feasible and safe for benign or pre-malignant lesions of pancreatic head. Moreover,it is oncological equivalent to pancreaticoduodenectomy with preservation of metabolic function without refractory cholangitis.
Adolescent ; Adult ; Aged ; Child ; Duodenum/surgery* ; Female ; Humans ; Male ; Middle Aged ; Pancreas/surgery* ; Pancreatectomy ; Pancreatic Neoplasms/surgery* ; Pancreaticoduodenectomy ; Postoperative Complications ; Retrospective Studies ; Young Adult

Objective: To learn about the noise exposure and health status of workers and analyze factors that may affect the health outcomes of workers in an auto manufacturing enterprise in Tianjin City. Methods: In September 2020, occupational hygiene survey, noise exposure level detection and occupational health examination data collection were carried out in an auto parts manufacturing enterprise. Chi square test and unconditional logistic regression analysis were used to analyze the health effects of noise exposure and hearing loss of 361 noise exposure workers. Results: The rates of over-standard noise exposure, hearing loss and hypertension were 69.39% (34/49) , 33.24% (120/361) and 11.36% (41/361) , respectively. There were upward trends on age and noise-working years for hearing loss and hypertension rates (χ(2)=-5.95, -6.16, -2.81, -2.74, P<0.05) . Unconditional logistic regression analysis showed that age>35 years old, noise exposure length of service >10 years and noise L(EX, 8 h)>85 dB (A) were risk factors for hearing loss (OR=3.57, 95%CI: 1.09, 11.75; OR=4.05, 95%CI: 1.97, 8.25; OR=1.75, 95%CI: 1.00, 3.05; P=0.036, 0.001, 0.047) . Conclusion: This company has a high rate of job noise exceeding the standard, and noise-exposed workers have more serious hearing loss. Age, noise exposure and high noise exposure are risk factors for hearing loss.
Adult ; Automobiles ; Deafness ; Hearing Loss, Noise-Induced/etiology* ; Humans ; Hypertension/complications* ; Noise, Occupational/adverse effects* ; Occupational Diseases/complications* ; Occupational Exposure/analysis*

Collagen α3 (IV) chains are one of the major constituent components of the basement membrane in the mammalian testis. Studies have shown that biologically active fragments, such as noncollagenase domain (NC1)-peptide, can be released from the C-terminal region of collagen α3 (IV) chains, possibly through the proteolytic action of metalloproteinase 9 (MMP9). NC1-peptide was shown to promote blood-testis barrier (BTB) remodeling and fully developed spermatid (e.g., sperm) release from the seminiferous epithelium because this bioactive peptide was capable of perturbing the organization of both actin- and microtubule (MT)-based cytoskeletons at the Sertoli cell-cell and also Sertoli-spermatid interface, the ultrastructure known as the basal ectoplasmic specialization (ES) and apical ES, respectively. More importantly, recent studies have shown that this NC1-peptide-induced effects on cytoskeletal organization in the testis are mediated through an activation of mammalian target of rapamycin complex 1/ribosomal protein S6/transforming retrovirus Akt1/2 protein (mTORC1/rpS6/Akt1/2) signaling cascade, involving an activation of cell division control protein 42 homolog (Cdc42) GTPase, but not Ras homolog family member A GTPase (RhoA), and the participation of end-binding protein 1 (EB1), a microtubule plus (+) end tracking protein (+TIP), downstream. Herein, we critically evaluate these findings, providing a critical discussion by which the basement membrane modulates spermatogenesis through one of its locally generated regulatory peptides in the testis.