Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(Ⅳ)prodrug(C8Pt(Ⅳ))and Cet.The so-called antibody-platinum(Ⅳ)prodrugs conjugates,named Cet-C8Pt(Ⅳ),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(Ⅳ)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(Ⅳ)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(Ⅳ)prodrugs conjugates.

BACKGROUND: Hepatic fibrosis (HF) is a histopathological change in the process of long-term liver injury caused by cytokine secretion and internal environment disturbance, resulting in excessive liver repair and fiber scar. Nogo-B protein is widely distributed in peripheral tissues and organs and can regulate the migration of endothelial cells by activating TGFb1 in vascular remodeling after injury. Nogo-B has been shown to promote organ fibrosis. This study was to determine the role of Nogo-B in HF. METHODS: An HF model was built by intraperitoneal injections with 20% carbon tetrachloride. Localization of Nogo-B was detected by FISH. The interaction between Nogo-B and BACE1 was confirmed by Co-IP. Autophagy flux was analyzed using tandem mRFP-GFP-LC3 fluorescence microscopy, electron microscopy, and western blotting. Detection of serum AST and ALT and H&E staining were utilized to detect the degree of liver injury. The HF was evaluated by Masson trichromatic staining. RT-qPCR, western blotting, and immunofluorescence were employed to detect relevant indicators. RESULTS: Reducing Nogo-B suppressed AST and ALT levels, the accumulation of collagen I and a-SMA, and expressions of pro-fibrotic genes in mouse liver. BACE1 was a potential downstream target of Nogo-B. Nogo-B was upregulated in TGF-b1-activated hepatic stellate cells (HSCs). Knocking down Nogo-B caused the downregulation of profibrotic genes and inhibited viability of HSCs. Nogo-B knockdown prevented CCL4-induced fibrosis, accompanied by downregulation of extracellular matrix. Nogo-B inhibited HSC autophagy and increased lipid accumulation. BACE1 knockdown inhibited HSC autophagy and activation in LX-2 cells. CONCLUSION Nogo-B knockdown prevents HF by directly inhibiting BACe1-mediated autophagy.

Objective:To retrieve the relevant guidelines and expert consensus on self-management of patients with high-risk foot diabetes, and analyze the content of high-quality guidelines and expert consensus recommendations, so as to provide a reference for the construction of a guidance program for self-management of patients with high-risk foot diabetes.Methods:Computer-retrieved clinical practice guidelines and expert consensus for self-management of patients with high-risk foot for diabetes from databases, guideline networks, and related professional websites. The search period was from January 1, 2012 to June 5, 2022. The quality of the included literature was evaluated and the evidence was extracted and integrated by 2 researchers. Experts were invited to evaluate the summarized evidence.Results:According to the quality of literature, a total of 12 guidelines (10 at level A and 2 at level B) and 3 expert consensus (expert discussion and decision) were included, and 8 themes were defined as regular follow-up, self-assessment, foot and decompression management, exercise management, nutrition management, indicator management, psychological management, and health education, a total of 28 recommendations. Among them, there were 23 A-level recommendations and 5 B-level recommendations.Conclusions:The quality of the guidelines and expert consensus included in this study is high,the recommended level of the summarized evidence is high. This study provides the reference and basis for the clinical staff to construct and guide the clinical practice of self-management of high-risk diabetic foot patients.

Objective:To investigate the status quo of knowledge, attitude and practice of enterostomal therapists (ET) in chronic wound pain management and analyze its influencing factors, so as to provide references and suggestions for continuous improvement of wound pain management.Methods:The convenient sampling method was used to investigate 260 ET objects. The survey tools were a self-designed General Information Questionnaire and questionnaires on knowledge, attitude and practice of ET on chronic wound pain.Results:A total of 260 questionnaires were distributed and 238 were valid. The score of ET on chronic wound pain knowledge questionnaire was (5.90±1.49) , the score of ET on chronic wound pain attitude questionnaire was (25.74±3.57) and the score of ET on chronic wound pain management practice questionnaire was (53.28±12.52) . The results of multiple linear regression showed that professional title, working years in wound care and working experience in relevant departments of oncology were the influencing factors of knowledge, attitude and practice of ET in chronic wound pain management ( P<0.05) . Conclusions:ET lacks knowledge of chronic wound pain and has acceptable attitudes, and his practical behaviors need to be strengthened urgently.Hospital administrators vigorously develop full-time ET and implement multidisciplinary collaboration to manage wound pain. When selecting ET training personnel, it is recommended that nurses at or above the intermediate level be the target of training. For ET, it is necessary to continuously improve professional titles and re-learn, and continuously accumulate experience in practice. For ET schools, a wound pain training knowledge system based on job competence should be established, and corresponding training should be carried out for wound specialist nurses.

Objective To investigate the epidemiological characteristics of a family clustering of COVID-19. Methods Field epidemiological survey was conducted. Result Case 1 of the long-term residents from Hubei province was the source of infection of this family clustering. There were 6 cases (from case 2 to case 7) infected in the whole incubation period. The incubation period was more than 14 days for 3 of the second-generation cases. Routes of transmission include respiratory droplets (from case 1 transmitted to case 6, from case 1 to her family members) and closecontact (from case 1 to other cases in her family). All the age groups were generally susceptible, while elderly were easier to progress to critically ill. Besides respiratory symptoms, there were also gastrointestinal symptoms, of which diarrhea was the most common one. Conclusion Family clustering had been an important part for COVID-19 cases.

Objective: To investigate the clinical research of Guo's Liulian therapy in treating acute pancreatitis intestinal mucosal barrier dysfunction and provide reference for the patients with acute pancreatitis. Methods: The 68 patients with acute pancreatitis who were admitted to our hospital from September 2016 to May 2018 were selected as study subjects. According to the random number table method, the patients were divided into the observation group and the control group, with 34 cases in each group. The patients in the control group were treated with conventional western medicine. The patients in the observation group were treated with Guo's Liulian therapy on the basis of the above treatment. The time of intestinal paralysis was compared between the two groups. The changes of intestinal mucosal barrier function and serum inflammatory factor related indexes before and after treatment were analyzed in the two groups. The difference of therapeutic effects between the two groups was observed. Results: In the observation group, the abdominal pain relief time, abdominal distention relief time, bowel sound recovery time, and first bowel anus defecation time were significantly lower than those in the control group (t=7.621, 5.332 6.625, 8.762, all Ps<0.01). After treatment, serum LPS, DAO, ET, D-lactic acid, TNF-α, IL-1, IL-6, IL-8, and IL-10 and urine L/M were significantly lower in the observation group, while the serum ITF and MFG-E8 were significantly higher in the observation group (t=9.856, 6.974, 9.784, 16.068, 9.550, 12.506, 22.343, 16.625, 6.774, 23.469, 20.118, 23.031, all Ps<0.01). Conclusions The Guo's Liulian therapy treatment of acute pancreatitis in patients with intestinal mucosal barrier dysfunction can reduce the palsy remission time, reduce inflammation, increase serum ITF, MFG-E8 levels, repair of intestinal permeability, and improve the intestinal barrier function.

OBJECTIVE: To summarize and analyze the postoperative short-term complications of laparoscope-assisted transanal total mesorectal excision (taTME) for rectal cancer patients after neoadjuvant therapy. METHODS: A prospectively established database on taTME patients at Peking University Cancer Hospital was screened with the following conditions: data retrieval from June 2016 to August 2018, pathologically confirmed adenocarcinoma, receiving preoperative neoadjuvant chemoradiotherapy or chemotherapy. The transabdominal procedure and the transanal procedure were performed simultaneously in the taTME operation. Occurrence of complications during perioperative period (within postoperative 3 months) in these patients, especially anastomosis-related complications and their management were analyzed. The relevant complications were recorded according to the Clavien-Dindo (CD) grading criteria. The severity of anastomotic leakage and anastomotic stenosis was evaluated according to criteria developed by the International Rectal Cancer Research Group. RESULTS: A total of 29 patients were enrolled in this study. In the 29 patients, 25 (86.2%) were male and 4 (13.8%) were female, the median age was 60 (range, 30 to 72) years, the median body mass index was 25.8 (range, 19.8 to 36.4) kg/m, the median distance from the tumor to anal verge was 4 (range, 2 to 8) cm. All the patients completed laparoscope-assisted taTME operations successfully without conversion to laparotomy, intra-operative severe complication or death. The median operation time was 300 (range, 198 to 405) minutes, and the median intra-operative blood loss was 100 (range, 50 to 200) ml. All the TME specimens were complete according to the Nagtegaal standard. All the patients underwent prophylactic ileostomy. Hartmann procedure was performed in one case due to poor blood supply in the proximal bowel without the possibility of anastomosis. Anal sphincter preservation rate was 96.6% (28/29). The median postoperative exhaust time was 2 (range, 1 to 10) days, and the median postoperative hospital stay was 9 (range, 7 to 24) days. Fifteen patients (51.7%) had postoperative complications, among which serious complication (CD grade IIIb and above) accounted for 6.9% (2/29). No perioperative death was observed. Five patients (17.2%) presented anastomosis-related complications, including 2 cases of grade C anastomotic leakage due to anastomotic rupture, who underwent abdominal perineal resection 1 month after operation; 2 cases of grade B anastomotic leakage, who improved after conservative treatment; 1 case of grade A anastomotic stenosis, who improved with anal expansion 1 month after operation. The incidence of postoperative infection was 24.1% (7/29), including 6 cases of pelvic infection and 1 case of trocar site infection, all of which were CD grade II. One case had incomplete intestinal obstruction (CD grade II); 1 case had gastroplegia; 1 case had abdominal trocar hernia. All the patients were followed up for a median of 12.0 (range, 3.9 to 29.9) months. Seven cases did not undergo ileal stoma closure. The anal sphincter preservation rate was 75.9% (22/29). CONCLUSION Pelvic infection and anastomosis-related complications are common after laparoscope-assisted taTME surgery for rectal cancer patients following neoadjuvant chemoradiotherapy, which require active management and appropriate treatment.
Adult ; Aged ; Anal Canal ; Female ; Humans ; Laparoscopes ; Male ; Middle Aged ; Neoadjuvant Therapy ; Postoperative Complications ; Rectal Neoplasms ; therapy

Objective To investigate the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) on inflammatory response,nerve damage,and outcomes in patients with severe traumatic brain injury (sTBI).Methods Altogether 120 sTBI patients were selected from January 2013 to September 2014 in Jinjiang Hospital of Traditional Chinese Medicine and divided with a random number table into experimental group (with ω-3 PUFA supplementation,n =60) and control group (without ω-3 PUFA supplementation,n =60).Sixty blood samples from healthy people visiting the physical examination clinic were collected as normal controls.The serum levels of tumor necrosis factor-α (TNF-α),interleukin (IL)-1,IL-6,S100B and neuron-specific enolase (NSE) were detected with enzyme-linked immunosorbent assay (ELISA).Glasgow Coma Scale (GCS) score,Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score and outcomes of the two groups were compared.Results The serum levels ofTNF-α,IL-1,IL-6,S100B,and NSE protein significantly increased in patients with sTBI compared with the normal controls (all P ＜ 0.05).Compared with the control group,the serum levels of inflammatory related factors (TNF-α,IL-1,IL-6) in the experimental group were significantly decreased on the 3rd day [(213.81 ±29.33) μg/L vs.(267.76 ±31.35) μg/L,(121.81 ± 10.63) μg/L vs.(152.60 ± 11.45) μg/L,(81.89 ± 8.34) μg/L vs.(106.62 ± 10.35) μg/L,all P ＜ 0.05],S100B and NSE protein expressions were significantly decreased on the 7th day [(1.32 ± 0.09) μg/L vs.(1.67 ± 0.12) μg/L,(12.57 ± 1.53) μg/L vs.(17.57 ±2.30) μg/L,both P ＜0.05].Compresd with the control group,the experimental group showed significantly higher GCS scores (9.32 ± 1.64 vs.7.14 ± 1.30,P =0.02) and significantly lower APACHE Ⅱ scores (14.37 ± 2.27 vs.17.00 ± 1.85,P =0.04) on the 14th day.Compresd with the control group,the experimental group showed lower mortality during the follow-up [11.7％ (7/60) vs.15.0％ (9/60)],but with no significant differences (P =0.49).Conclusion Supplementation of ω-3 PUFA could exert neuroprotective effect by effectively regulating inflammatory response and reducing the damages to glia and neurons in patients with sTBI,which is a promising agent for clinical application.

Objective To understand the incidence and death patterns of viral hepatitis in China and provide evidence for the prevention and control of viral hepatitis.Methods The analysis was conducted on the incidence and death data of viral hepatitis published by National Health and Family Planning Commission during 2004-2013.Results The incidences of viral hepatitis in Guizhou,Yunnan,Tibet,Gansu,Qinghai,Ningxia and Xinjiang provinces (autonomous region) were high.The major forms were hepatitis B (80.63/100 000) and hepatitis C (9.68/100 000),accounting for 80.90％ and 9.25％ of the total reported viral hepatitis cases respectively.The incidences of hepatitis A and unidentified hepatitis decreased and the incidence of hepatitis B,C and E increased during this period.During the 10 years,10 008 deaths caused by viral hepatitis were reported (1 001 deaths per year).The reported deaths caused by hepatitis A,hepatitis E and unidentified hepatitis decreased during this period.The reported deaths caused by hepatitis B were in a downward trend,but the constituent in total cases remained high.The reported deaths caused by hepatitis C were in an upward trend.Conclusion During 2004-2013,the overall incidence of viral hepatitis showed no downward trend in China.The incidence of hepatitis B remained high,and the incidence of hepatitis C showed an obvious upward trend.The overall death rate and case fatality rate of viral hepatitis showed a downward trend,but hepatitis B remained the main cause of viral hepatitis related death,and the death caused by hepatitis C was in increase.Hepatitis B and hepatitis C are the major targets in the prevention and treatment of viral hepatitis in China,and the 7 western provinces (autonomous region) with high incidences are the key regions of the prevention and control.

OBJECTIVE To investigate the bacterial contamination of office telephones and computers in an infectious disease hospital to provide evidence for their disinfection.METHODS A total of 206 bacterial samples were collected from 73 telephones and 30 computers in offices in our hospital to determine the bacterial contamination of these office tools.RESULTS The contamination rate was 100% and sanitary qualification rate 32.5%.The highest bacterial colony count was 46 CFU/cm2 and the lowest one 2 CFU/cm2,The sanitary qulification rate of the telephones and computers in clean region was only 30.95%.CONCLUSIONS There was severe bacterial contamination in office telephones and computers,which should be paid close attention to.