Objective:To delineate the clinical characteristics and outcomes associated with severe cardiac toxicity during the preconditioning phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aplastic anemia (AA).Methods:This retrospective case series study included 31 patients with severe AA who underwent allo-HSCT and were diagnosed with severe cardiac toxicity at the Hematology Department of Peking University People′s Hospital from August 2012 to June 2022. The clinical manifestations of severe cardiac toxicity observed during the preconditioning process were assessed. Patient survival was assessed using the Kaplan-Meier method.Results:In this cohort of 31 patients, the median follow-up period was 9 days (range: 4-365 days). Severe cardiac toxicity manifested within 6 days after the initial cyclophosphamide (Cy) administration. Twenty patients died within 30 days of initiating Cy preconditioning, of which 16 patients died due to severe cardiac toxicity within 25 days. Patients whose cardiac function improved within 30 days post-preconditioning showed a median survival duration of 222 days ( n=11). Troponin I (TNI) levels in patients who died within 30 days of initiating Cy preconditioning began increasing on day 5 post-Cy, peaking sharply by day 9 after a notable rise on day 8. B-type natriuretic peptide (BNP) levels in patients who died within 30 days of initiating Cy preconditioning started to rise from day 1, stabilized between days 2 and 5, and then doubled daily from days 6 to 8, remaining elevated thereafter. Notably, the initial increases in BNP and TNI correlated with electrocardiogram (ECG) signs of low voltage and T-wave inversion in 83.87% of cases ( n=26). Most patients ( n=28, 90.32%) were administered corticosteroid therapy. In those with restored cardiac function, the ejection fraction returned to >50% within 30 days of initiating Cy preconditioning. Conclusions:Patients with severe cardiac toxicity during the preconditioning phase of allo-HSCT typically exhibit early, sustained, and marked elevations in myocardial damage markers, including BNP and TNI, accompanied by ECG abnormalities following Cy administration, with BNP often increasing first. These indicators are associated with rapid disease progression and high mortality. Prompt initiation of treatment upon clinical diagnosis is critical for improving survival outcomes.

Objective:To design a multi-epitope antigen of norovirus(NoV)based on bioinformatics technology and to pre-pare and characterize it.Methods:Bioinformatics methods were used to construct and analyze the NoV multi-epitope antigen NoV-ZH.Recombinant proteins were prepared and characterized by prokaryotic expression system,and monoclonal antibodies were prepared by animal immunization and hybridoma technology,and initially applied in colloidal gold platform.Results:The designed multi-epitope antigen had a large proportion of random curls in the secondary structure,with theoretical molecular mass and isoelectric point(PI)of 13.1 ku and 7.16,which were stable and hydrophilic.It had good immunogenicity and could activate humoral and cellular immune re-sponses.The proteins prepared by ligating pET-28a(+)and pET-32a vectors with antigenic sequences were expressed as inclusion body proteins and soluble proteins,respectively.A pair of paired antibodies was obtained by animal immunization and hybridoma tech-nique,and applied to colloidal gold test strips with a sensitivity of 0.5 ng/ml,and the test strips could specifically bind two genotypes of NoV recombinant capsid proteins.Conclusion:The successful preparation and characterization of multi-epitope antigen of norovirus provides a reference for the subsequent exploration of NoV universal detection targets and the development of diagnostic raw materials.

Gallbladder carcinoma(GBC)is one of the most common malignant tumors in the biliary system,which is difficult to diagnose in the early stage due to its high degree of malignancy,invasiveness and lack of specific clin-ical manifestations.In this paper,we summarize ultrasound,CT and other imaging manifestations in the early stage of GBC,and describe the role of protein markers and microRNA marker as biomarkers in the diagnosis of early GBC.The enhanced understanding of the relevant features might help to improve the accuracy of the diagnosis of early gallbladder carcinoma.

Objective To evaluate the efficacy of XELOX regimen as neoadjuvant chemotherapy in the treatment of stage Ⅱ and Ⅲ colon cancer.Methods The clinical data of 50 patients with clinical stage Ⅱ(T4)Ⅲ colon cancer who underwent laparoscopic radical resection at general surgery department of our hospital from January 1,2012 to January 1,2021 were retrospectively analyzed.Patients were divided into neoadjuvant chemotherapy group(NACT)and adjuvant chemotherapy group(ACT)according to whether they received neoadjuvant chemotherapy with XELOX regimen.The general clinical data,adverse reactions of chemotherapy,surgical complications,operation time,intraoperative blood loss,hospitalization time,hospitalization cost,negative conversion rate of tumor markers,tumor remission rate,tumor downstaging rate,tumor response grade after chemotherapy,postoperative disease-free survival curve,and overall survival curve were retrospectively analyzed and compared among the groups.Results There were no significant differences in operative complications,postoperative exhaust time and hospital stay between NACT group and ACT group(P＞0.05).The adverse reactions of chemotherapy,the negative conversion rate of postoperative CEA and CA19-9,the duration of operation,the amount of bleeding,and the hospitalization cost in NACT group were significantly better than those in ACT group(P＜0.05).In terms of DFS and OS survival curves,with the extension of time,the decline of the NACT survival curve was smaller than that of the ACT group,and there was a significant difference in DFS survival curve(P＜0.05),but no significant difference in OS survival curve(P＞0.05).Conclusion XELOX neoadjuvant chemotherapy is safe and effective in the treatment of stage Ⅱ(T4)and stage Ⅲcolon cancer.

BACKGROUND:Internal tension-reduction technique is to reconstruct the anterior cruciate ligament through high-strength suture system combined with tendon.It can effectively reduce graft relaxation and frets by sharing the internal load of the knee joint,and has achieved good biomechanical results and clinical efficacy.However,whether it can reduce cartilage degeneration after anterior cruciate ligament reconstruction through stress sharing reduction has not been studied. OBJECTIVE:To investigate the effect of internal tension-reduction technique on articular cartilage degeneration in southern Yunnan small-ear pigs undergoing anterior cruciate ligament reconstruction. METHODS:Ten adult female Yunnan small-ear pigs were selected,and the ipsilateral knee Achilles tendon was taken from the left knee joint for anterior cruciate ligament reconstruction(normal group,n=10),and the ipsilateral knee Achilles tendon from the right knee joint combined with internal tension-reduction and augmentation system for anterior cruciate ligament reconstruction(tension-reduction group,n=10).One year after surgery,the experimental pigs were sacrificed,and the left and right knee cartilage was taken for hematoxylin-eosin staining,Safranin O-fast green staining,Osteoarthritis Research Society International scoring,and immunohistochemistry staining of type Ⅱ collagen,interleukin-1β,and tumor necrosis factor-alpha in the cartilage. RESULTS AND CONCLUSION:Hematoxylin-eosin staining showed that in the tension-reduction group,there were mild pathologic changes of osteoarthritis,with a low number of empty bone lacunae and no obvious pathological changes such as fibrosis or cell layer breakage;in the normal group,more severe cartilage damage,with an increased number of empty bone lacunae,loss of chondrocytes near the bone and even the formation of fissures.Safranin O-fast green staining indicated that the tension-reduction group had normal cartilage tissue thickness,flat cartilage surface,a neat cell arrangement in a polar pattern,and no swelling or apoptosis,while in the normal group,the thickness of cartilage tissue was obviously thinner,the cell arrangement was disordered with no polarity,the number of cells was reduced,obvious cartilage fractures and cartilage vacuoles formed,and the absence of cells near the central bone was obvious.The Osteoarthritis Research Society International score was significantly lower in the tension-reduction group than in the normal group(P＜0.05).Immunohistochemical findings showed that the protein expression of type Ⅱ collagen in cartilage tissue of the tension-reducing group was higher than that of the normal group(P＜0.05),and the protein expression of interleukin 1β and tumor necrosis factor ɑ in cartilage tissue was lower than that of normal group(P＜0.05).To conclude,internal tension-reduction technique can delay the degeneration of articular cartilage in Yunnan small-eared pigs following anterior cruciate ligament reconstruction.

Objective To analyze the epidemiological characteristics of hand-foot-mouth disease(HFMD)in Gan-zhou.Methods The epidemiological data of HFMD reported by the Infectious Disease Surveillance System,a sub-system of China Disease Prevention and Control Information System,from 2017 to 2020 were analyzed by descriptive methods.Enterovirus(EV)nucleic acid and typing detections via throat swabs,anal swabs or herpes fluid of patients was detected by real-time fluo-rescent polymerase chain reaction.The change in HFMD epidemic characteristics was compared between 2020 and 2017-2019.Results The incidence of HFMD in Ganzhou in 2020 was significantly lower than that from 2017 to 2019(x2=50.587,P＜0.05).In 2020,the incidence of HFMD in counties and districts of Ganzhou(except Huichang County)signifi-cantly decreased compared with that in 2017-2019(P＜0.05).From 2017 to 2019,the incidence of HFMD was obviously seasonal,with a high incidence in summer and autumn,and two significant incidence peaks were formed in June and September in 2017 and 2018,respectively.In 2019,there was a summer peak in June.The epidemic trend in 2020 was different,with a very low epidemic trend in summer and autumn,and a peak in winter.The incidence of HFMD in men,women and all ages in 2020 significantly decreased compared with that in 2017-2019(P＜0.05),and the age of onset was mainly distributed in 1-5 years,especially in children aged 1 to 3 years.There was a significant difference in the incidence of HFMD among different ages(P＜0.05).The positive rate of EV in Ganzhou in 2020 was lower than that from 2017 to 2019(x2=47.273,P＜0.05).The positive rate of EV in January,March to September in 2020 was significantly lower,and the positive rate of EV in November,December 2020 was significantly higher than that in the same period in 2017 to 2019(P＜0.05).Strain CA16 showed an increasing trend year by year from 2017 to 2019,and became the dominant strain in 2019.The proportion of patients infected with CA6 strain was on the fise from 2018 to 2020,and CA6 became the dominant strain in 2020.Conclusion The HFMD in Ganzhou has obvious population characteristics and seasonality,and the pathogen spectrum is constantly changing.

Objective:To identify pathogenic genes in 3 cases of piebaldism, and to explore the genotype-phenotype relationships in piebaldism.Methods:Clinical data were collected from 3 patients with piebaldism and their parents at the Department of Dermatology, Henan Provincial People′s Hospital from January 2019 to December 2021. Peripheral blood samples were obtained from them and 100 unrelated healthy controls, and DNA was extracted. Whole-exome sequencing technology was used to screen genetic variation sites, and then Sanger sequencing was performed for verification. The deleteriousness of genetic variants was evaluated by using pathogenicity analysis software tools.Results:Case 1: a 23-year-old male patient presented with white patches on the forehead, chest, and abdomen for 23 years, and his parents had no similar symptoms; case 2: a 1-year- and 5-month-old male infant presented with white patches on the forehead and abdomen for 1 year, and his parents had no similar symptoms; case 3: a 6-year-old male child presented with white patches on the forehead and limbs for 6 years, and his parents had no similar clinical manifestations. Genetic testing showed that a missense mutation c.2033T>C (p.L678P) in exon 14 of the KIT gene, a splice site mutation c.2485-1G>C in exon 18 of the KIT gene, and a heterozygous missense mutation c.2346C>G (p.F782L) in exon 16 of the KIT gene were identified in the case 1, 2, 3 respectively, but no above mutations were identified in the patients′ parents or 100 unrelated healthy controls. The 3 genetic variants were all novel pathogenic mutations, and all were deleterious mutations.Conclusions:Three novel pathogenic mutations in the KIT gene were identified in the 3 cases of piebaldism, namely c.2033T>C (p.L678P), c.2485-1G>C, and c.2346C>G (p.F782L). It was further verified that the severity of piebaldism was closely related to the type and location of KIT gene mutations.

【Objective】 To summarize the clinicopathological features and prognosis of young patients (18-40 years old) with non-clear cell renal cell carcinoma (nccRCC) treated in a single center to provide reference for the diagnosis and treatment of similar patients. 【Methods】 Clinical data of 113 nccRCC patients treated during Jan. 2012 and Aug. 2022 were retrospectively analyzed, including 57 males (50.4%) and 56 females (49.6%). The average age of onset was (31.6±5.8) years. Among all patients, 57 had lesions (50.4%) on the left side, and 56 (49.6%) on the right side. Young patients undergoing renal cancer surgery accounted for approximately 12.4% of the total number of renal cancer patients undergoing surgery, and nccRCC accounted for 34.8% of the total number of cases. 【Results】 Minimally invasive surgery (laparoscopic or robot-assisted) was performed in 102 cases (90.3%), and open surgery in 11 cases (9.7%). Fifty-five cases (48.7%) underwent partial nephrectomy and 58 (51.3%) radical nephrectomy. Among them, 11 patients (9.7%) developed tumor thrombi. All surgeries were successful with no serious complications. The pathological types included 32 cases (28.3%) of chromophobe renal cell carcinoma, 25 cases (22.1%) of MiT family translocation renal cell carcinoma, and 20 cases (17.7%) of papillary renal cell carcinoma. The total proportion of the three pathological subtypes reached 68.1%. After 46 (2-115) months of follow-up, 8 cases (7.8%, 8/102) developed tumor metastasis and 2 died. 【Conclusion】 The nccRCC is rare in young patients. The major pathological type is chromophobe, and the major treatment method is minimally invasive surgery. Most pathological types have good long-term prognosis, while patients with tumor thrombi have a high risk of metastasis and poor prognosis.

Objective:To evaluate the safety and feasibility of transumbilical single-port transabdominal preperitoneal hernioplasty plus cholecystectomy (SILS-TAPP+LC).Methods:The clinical data of 52 adult patients who underwent [SILS-(TAPP+LC)] from Mar, 2019 to Oct, 2021 at the Affiliated Hospital of Nantong University were retrospectively analyzed.The perioperative indicators, postoperative complications and follow-up data were analyzed.Results:All operations were successfully completed without conversion to open or multi-port laparoscopic surgery.The duration of surgery was (49.2 ± 7.5) min. Three patients experienced gallbladder rupture, and there was no bladder or intestinal injury during the surgery.During the 20-24 months of postoperative follow-up period,4 patient developed seroma in the postoperative period, 4 patients complained foreign body sense in the inguinal region, 3 patients reported chronic pain, but no other complications, such as biliary fistula, recurrence, mesh infection, or trocar hernia, were observed.Conclusion:SILS-(TAPP+LC) was a safe and feasible approach associated with little postoperative pain and rapid recovery.

Objective To analyze the risk factors of coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2M) in Suining area, and build a risk prediction model to provide theoretical basis for the prevention and treatment of CHD in PATIENTS with T2M. Methods A total of 476 T2M patients treated in our hospital from January 2021 to December 2021 were selected and divided into experimental group (n=79) and control group (n=397) according to whether they had coronary heart disease. The angiographic characteristics of coronary artery lesions in patients with T2M combined with coronary heart disease were observed. Age, sex, body mass index (BMI), smoking, alcohol consumption , T2M course, FBG, FINS, HOMA, TC, LDL-C, SBP, DBP and UA levels of all patients were analyzed. Univariate analysis and Logistic regression were used to analyze the influencing factors of coronary heart disease and establish a risk prediction model. ROC curve was used to predict the efficiency of the model. Results A total of 79 cases (16.60%) of patients with T2M complicated with coronary heart disease, including 64 cases (81.01%) of patients with T2M complicated with coronary artery disease. Mild stenosis in 5 cases (6.33%), moderate stenosis in 20 cases (25.32%) and severe stenosis in 54 cases (68.35%); The mean age, smoking proportion, BMI, T2M course and the levels of FBG, FINS, HOMA-IR, TC, LDL-C, SBP, DBP and UA in experimental group were significantly higher than those in control group (P<0.05). Multivariate logistic regression analysis showed that advanced age, increased SBP, increased LDL-C, and increased FBG were independent risk factors for CORONARY heart disease in T2M patients in Suining area (OR=1.476 , 2.674 , 2.984 , 3.572 , P<0.05). According to the above four independent factors and their corresponding regression coefficients, the expression of risk prediction model was P=1/[1+e^{-(-0.513+0.919×(old age)+1.129×(increased SBP)+ 1.724×(increased FBG)+ 1.529×(increased LDL-C)}]. ROC curve was used to analyze the predictive performance of the regression model. The results showed that the AUC of the risk prediction model for coronary heart disease in T2M patients was 0.728, 95% CI (0.651-0.829). Conclusions T2M patients in Suining have a high risk of coronary heart disease. For elderly patients with elevated SBP, LDL-C and FBG, the risk of coronary heart disease can be assessed by predictive model and targeted intervention measures can reduce the risk of coronary heart disease in T2M patients.