Objective:To investigate the genetic, clinical, and post-treatment characteristics of patients with glycogen storage disease type Ⅲ (GSD Ⅲ).Methods:A retrospective cohort analysis was performed on the genetic and clinical data of 26 cases with GSD Ⅲ who visited the Children's Hospital affiliated with Fudan University from June 2017 to December 2023. The patients were divided into non-missense variation and missense variation groups according to the types of mutation in the AGL gene.The correlation between genotype and phenotype was analyzed. All patients were treated with uncooked cornstarch after diagnosis. The changes before and after treatment were compared in patients who underwent more than twelve months of follow-up. A P value of <0.05 was used to denote statistical significance. Results:Among the 26 cases enrolled, 13 were female and 13 were male, and the median age of diagnosis was 28 (6 to 134) months. A total of thirty-five different types of AGL gene variation were detected, with c.1735+1G＞T (9/52, 17.3%) as the hotspot variation. The common clinical manifestations were elevated aminotransferases (26/26, 100%), hepatomegaly (25/26, 96.2%), fasting hypoglycemia (25/26, 96.2%), hyperketonemia (16/18, 88.9%), hypertriglyceridemia (TG) (20/26, 76.9%), elevated CK (16/25, 64.0%), and an abnormal electrocardiogram (12/16, 75.0%). Four cases (15.4%) had symptoms of myopathy at diagnosis. Liver biopsy was performed in eighteen cases, among whom 83.3% (15/18) had liver fibrosis≥S2. The number of cases with elevated levels of CK ( P＝0.031) and ALT ( P＝0.038)was pronounced in the non-missense variation group compared to that in the missense variation group. There were no statistically significant differences in age, height, liver size, degree of fibrosis, fasting blood glucose (Glu) and TG ( P>0.05). The median follow-up time of 14 cases was 40.5 (20-73) months, with improvement in body stature, reduced liver size, decreased ALT and TG, and improved Glu. However, four (28.6%) cases had new myopathy symptoms with raised CK ( P<0.05) and with advancing age, increased ALT diminished while CK level elevated ( P<0.05). Conclusions:The common clinical manifestations at the early stage of the GSD Ⅲdiagnosis are elevated aminotransferases, hepatomegaly, fasting hypoglycemia, hyperketonemia, high triglycerides, elevated CK, and fibrotic liver in China. Myopathy symptoms may arise following uncooked cornstarch treatment; however, there is significant improvement in height, liver-related, and metabolic parameters.

Objective To investigate the epidemiological characteristics of Salmonella infection in foodborne diseases in Shanxi Province, and to provide a scientific basis for the prevention and control of Salmonella infection. Methods Automatic microbial biochemical identification system was used to identify Salmonella , and descriptive epidemiological methods were used to analyze the characteristics of Salmonella infections in foodborne diseases in Shanxi Province from 2016 to 2021. Results The basic information of 10 037 cases of foodborne diseases and their Salmonella detection results were analyzed. The detection rate of Salmonella was 5.25%, and the main serotype was Salmonella enteritidis (209/522). The positive detection rate of Salmonella in the 0-10 years old age group was the highest (6.04%), and the difference was statistically significant (χ²= 19.23, P = 0.01). The positive detection rate of Salmonella in kindergarteners was the highest at 10.71%, and there was a significant difference in the positive detection rate among different occupations (χ²= 43.31, P < 0.05). The detection rate of bulk foods (5.16%) was higher than that of pre-packaged foods (3.70%), and the difference was statistically significant (χ²= 4.43, P = 0.04). Cases involving food stores had a higher Salmonella detection rate (9.54%), and the peak period of Salmonella infection was from May 24 to August 23. Conclusion The incidence of Salmonella infection in foodborne diseases is high in summer and autumn. Foods in food stores and bulk foods are more likely to cause Salmonella infection. Supervision and management of food stores should be strengthened, and special attention should be paid to children in kindergartens during the epidemic peak.

Objective:To investigate the clinical effect of free superficial iliac circumflex artery perforator flap with different arterial anastomosis methods for repairing soft tissue defects of limbs.Methods:A retrospective cohort study was used to analyze the data of 60 patients with soft tissue defects of limbs treated in Ningbo No.6 Hospital from March 2017 to March 2020, including 38 males and 22 females, aged 21-57 years［(35.6±3.1)years］. The wounds were located on the upper limb in 33 patients and the lower limb wound in 27 patients. The defect area was 4.5 cm × 2.0 cm-17.0 cm × 8.0 cm. All patients received debridement and vacuum sealing drainage (VSD) in stage I, and free superficial iliac circumflex artery perforator flap transplantation in stage II. The flap area was 4.9 cm × 2.6 cm-17.0 cm × 8.0 cm. According to the different anastomotic vessels, the superficial iliac circumflex artery was anastomosed end-to- side to the radial artery in 25 patients, the ulnar artery in 8, the dorsalis pedis artery in 18 and the anterior tibial artery in 9. Flap healing and healing time were detected. Texture and appearance of the flap were observed at the last follow-up. The appearance of the donor area was evaluated by Vancouver scar scale (VSS), and the satisfaction rate of appearance of the recipient area was measured by numerical score.Results:All patients were followed up for 5-15 months［(7.1±1.3)points］. All flaps survived successfully after operation, including arterial crisis in 4 patients, among which 2 had flap perforator anastomosed with the radial artery, 1 with the ulnar artery and 1 with the dorsalis pedis artery. There was no significant difference in flap crisis after end-to-side arterial anastomosis in different recipient areas ( P>0.05). For patients with flap perforator anastomosed with the radial artery, the ulnar artery, the dorsalis pedis artery and the anterior tibial artery, the flap healing time was 15(14, 16)days, 15(14, 16)days, 14.5(14，16)days and 14(14，15.5)days, respectively (all P>0.05). The flaps showed sufficient elasticity and soft texture at the last follow-up. For patients with flap perforator anastomosed with the radial artery, the ulnar artery, the dorsalis pedis artery and the anterior tibial artery, the VSS of the donor area was (10.2±1.5)points, (10.9±1.6)points, (9.4±1.5)points and (9.8±1.5)points at the last follow-up (all P>0.05), and the satisfaction rate of appearance of the recipient area was 9 (8, 10)points, 9(8, 9)points, 9(8, 9)points and 8(8, 9.5)points at the last follow-up ( P>0.05), showing that all patients were satisfied with the appearance of the wound. Conclusions:The transplantation of free superficial iliac circumflex artery perforator flap with different arterial anastomosis methods is safe and reliable in repairing soft tissue defects of limbs with advantages of low occurrence of postoperative vascular crisis, good flap survival, no influence on flap healing by different anastomotic vessels, hidden donor area with small scar and satisfactory appearance of the recipient area. It can be used as one of the common vascular repair methods for free tissue flap transplantation.

【Objective】 Until now, most clinical and basic studies on Kashin-Beck disease (KBD) have focused on the visible deformed extremities, and there is a lack of reports concerning their spinal features, especially for the atlantoaxial joint. The purpose of this study was to determine the prevalence and radiographic features of atlantoaxial dislocation (AAD) in KBD in adult patients. 【Methods】 The prevalence and radiographic features of AAD were determined by the basic information collected, clinical symptoms, and lateral and dynamic plain radiography in 111 KBD patient and 120 non-KBD participants. In the KBD group, AAD and non-AAD patients were compared in age, gender, height, weight, BMI, smoking history, chronic history, disease duration and grade of disease so as to identify the related factors of the occurrence of AAD. 【Results】 Symptoms at the neck or neurological manifestations were present in 17.5% (21/120) in the non-KBD population and 39.6% (44/111) patients with KBD. AAD case was not detected in the non-KBD population, while in 16.2% (18/111) of KBD patients in the endemic area. The prevalence was higher in the KBD patients than in the non-KBD population, and there was a significant difference in the detection rate of AAD between the two groups (χ²=21.10, P<0.001). Plain radiography demonstrated that there were 10 (55.6%) cases with separation of the odontoid process and the other 8 (44.4%) cases with hypoplasia of odontoid process. Anterior AAD was noted in 12 (66.7%) patients and posterior AAD in 6 (33.3%) cases based on the displacement direction, while 16 (88.9%) cases were reducible and 2 (11.1%) cases were irreducible on the basis of the reducibility. Comparing the 93 patients with non-AAD KBD patients and 18 patients with AAD patients, there was no significant difference in age, sex, BMI, history of medical disease or smoking (all P>0.05). There were significant differences in height, weight, disease duration and grade of disease between AAD and non-AAD patients (all P<0.05). 【Conclusion】 KBD can cause the occurrence of atlantoaxial dislocation by inducing separation or hypoplasia of the odontoid process. This research may provide clinical evidence for screening, earlier prevention and treatment of atlantoaxial dislocation in adult KBD patients.

Objective:To deliver understanding of the latest research progress on clinical trials and approval of dermatological drugs in China in 2020.Methods:A registration and information disclosure platform for drug clinical studies and a query system for domestic and imported drugs in the National Medical Products Administration of China were searched for registered clinical trials and approved dermatological drugs, respectively. The number and stages of clinical trials, indications and classification of involved products, and listed dermatological drugs in 2020 were summarized and depicted.Results:There were 157 dermatological drug trials registered in China in 2020, accounting for 6.16% of all the 2 548 clinical drug trials, including 127 (80.9%) initiated by Chinese pharmaceutical enterprises and 25 (15.9%) international multicenter trials. Among the 127 drug trials initiated by Chinese pharmaceutical enterprises, bioequivalence trials were mostly common, accounting for 55.9% (71/127) . Compared with global pharmaceutical enterprises, domestic pharmaceutical companies initiated significantly decreased proportions of international multicenter trials (1.9% [3/157] vs. 14.0% [22/157], P < 0.001) , but significantly increased proportions of phaseⅠclinical trials and bioequivalence trials (24.4% [31/127] vs. 10.0% [3/30], 55.9% [71/127] vs. 0, respectively, both P < 0.001) . Totally, 90 kinds of dermatological drug were involved in all the trials, psoriasis, atopic dermatitis and melanoma were the most common indications, and innovative drugs accounted for 53.3% (48/90) ; the proportion of innovative drugs was significantly lower in domestic pharmaceutical companies than in global pharmaceutical companies (43.2% [32/74] vs. 16/16, P < 0.001) . In addition, 28 dermatological drugs developed by 22 pharmaceutical companies were approved in China in 2020, of which 21 drugs were developed by domestic pharmaceutical companies. Conclusion:Clinical drug trials carried out by domestic pharmaceutical companies mostly focus on generic drugs, and it is still necessary for domestic pharmaceutical companies to further improve the innovation ability.

Objective:To investigate the clinical application and effect of end-to-side anastomosis in personalised free ilioinguinal flap transfer.Methods:From March, 2015 to July, 2020, 88 patients with soft tissue (bone) defect of limbs were treated. Different ilioinguinal flaps were designed according to the wound condition of patients, which were 48 cases of free superficial circumflex iliacartery perforator flap, 7 cases of free superficial epigastric artery perforator flap, 19 cases of composite tissue flap with iliac bone, 8 cases of combined flap of superficial circumflex iliac artery and superficial abdominal wall artery, and 6 cases of superficial circumflex iliac artery and superficial abdominal wall artery lobulated flap. The area of the flap was 4.0 cm×6.0 cm-10.0 cm×30.0 cm. The artery and recipient artery were anastomosed end-to-side: 36 cases to radial artery; 12 cases to ulnar artery; 18 cases to dorsalis pedis artery; 15 cases to anterior tibial artery; 7 cases to posterior tibial artery. Venous anastomosis of skin flap: 42 cases were anastomosed with 2 veins, which were superficial vein of the same name and accompanying vein; 46 cases were anastomosed with 1 superficial vein of the same name. The accompanying vein of the flap was anastomosed end-to-side with the accompanying vein of the main artery of the recipient area, and the superficial vein of the same name was anastomosed end-to-end with the accompanying vein or subcutaneous superficial vein of the recipient artery. Follow-up includes flap blood supply, blood supply to the distal limbs, appearance of both the donor site and the recipient area, and patient satisfaction.Results:There were 83 cases of flaps survived successfully, and 5 cases of crisis. Among them, 2 cases had artery crisis at 48 h after surgery. After exploration, it was found that 1 case caused by arterial thrombosis, and 1 case compressed by the stapler that anastomoses the vein. The other 3 cases had venous crisis at 72 h after surgery: after exploration, it was found that caused by thrombosis at the venous anastomotic site. The average follow-up period was 10 (range, 3-24) months. All flaps survived after re anastomosis or vascular transposition. The donor site and recipient site of the flap healed well. The blood supply of the flap was good and the texture was soft. There was no blood supply disorder in the distal limb.Conclusion:The end-to-side anastomosis technique is suitable for all kinds of free flap transplantation in ilioinguinal region, with high vascular patency rate. It can not only solve the problem of thin vascular pedicle of donor site flap, but also retain the main artery of recipient limb without affecting the distal blood supply.

OBJECTIVE: To evaluate the expression of thymidylate synthase (TS) in myoepithelial cells (MECs) of salivary adenoid tissues and explore its clinical significance. METHODS: Immunohistochemical staining EnVision method was used to detect the expression of TS, P63, Calponin, CK5/6 and S-100 in 32 salivary gland specimens, including 10 non-neoplastic and salivary inflammation specimens, 11 mixed tumor specimens, 5 basal cell carcinoma specimens and 6 adenoid cyst carcinoma specimens. The specificity and sensitivity of TS as a specific molecular marker of salivary muscle epithelial cells were evaluated in comparison with P63, Calponin, CK5/6 and S-100. RESULTS: The expression pattern of TS in all the salivary gland tissue specimens was identical with that of p63. TS and P63 both showed strong immunohistochemical expressions in MECs of salivary adenoid tissue specimens. Calponin, CK5/6, and S-100 showed cytoplasmic/membranous expressions in the MECs. In addition, TS exhibited weak or moderate cytoplasmic expression in a few salivary gland epithelial cells, cancer cells and scattered stromal cells, with negative expression in the cell nuclei. The expression of TS in the MECs of all the salivary adenoid specimens was highly consistent with those of P63, Calponin, CK5/6 and S-100 (>0.05) Except for CK5/6 expression in Salivary inflammation and Salivary gland specimens. Kappa>0.75. The specificity and sensitivity of TS as a molecular marker of MECs were both 100%. CONCLUSIONS TS is a new specific marker of MECs for differential diagnosis of salivary gland tumors.
Adenoids ; Biomarkers, Tumor ; Carcinoma, Adenoid Cystic ; Epithelial Cells ; Humans ; Salivary Gland Neoplasms ; Thymidylate Synthase

OBJECTIVE: To investigate the effect of calcium channel blocker diltizem in reversing multi-drug resistance (MDR) and on metadherin expression in hepatocellular carcinoma cells and explore the molecular mechanism. METHODS: Hepatocellular carcinoma MHCC97H and 7402 cells were treated with diltiazem hydrochloride, a calcium channel blocker (0, 25, 50, 100, 200, and 400 μmol/L), for 12, 24, or 48 h. Wound healing assay was employed to assess the changes in the mobility and migration of the cells following the treatments, and the changes in the expression levels of metadherin mRNA and protein and P-gp protein were determined using RT-PCR and immunocytochemistry. RESULTS: Diltiazem hydrochloride could transiently inhibit the migration and movement of MHCC97H and 7402 cells in a time-and concentration-dependent manner ( < 0.05). Diltiazem hydrochloride at different concentrations also transiently up-regulated the expressions of metadherin mRNA and protein but did not inhibit the expression of P-gp protein in MHCC97H and 7402 cells. CONCLUSIONS Calcium channel blocker can transiently inhibit the migration of hepatocellular carcinoma cells and up-regulate the expression of metadherin mRNA and protein through a feedback mechanism, suggesting the potential risk of calcium channel blockers for promoting tumor progression during the treatment of malignant tumors.
Calcium Channel Blockers ; Carcinoma, Hepatocellular ; Cell Line, Tumor ; Diltiazem ; Humans ; Liver Neoplasms

OBJECTIVE: To generate a new strain of HBeAg transgenic mice using CRISPR/Cas9 technique. METHODS: Hepatitis B virus (HBV) HBeAg gene was cloned and inserted in the pliver-HBeAg expression frame at the site of Rosa26 gene using CRISPR/Cas9 and homologous recombination techniques to construct the pliver-HBeAg expression vector containing HBeAg gene. The linear DNA fragment containing HBeAg gene was obtained by enzyme digestion. Cas9 mRNA, gRNA and the donor vector were microinjected into fertilized eggs of C57BL/6J mice, which were then transplanted into the uterus of C57BL/6J female surrogate mice to obtain F0 generation mice. The F0 generation mice were identified by long fragment PCR to obtain F0 transgenic mice with HBeAg gene. The positive F0 generation mice were bred with wild-type C57BL/6J mice to produce the F1 mice, which were identified by PCR and sequencing. The positive F1 transgenic mice carrying HBeAg gene were backcrossed until the homozygous offspring transgenic mice were obtained. The genotypes of the offspring mice were identified. The expressions of HBeAg and HBeAb in the heterozygous and homozygous HBeAg transgenic mice were detected by automatic chemiluminescence immunoassay, immune colloidal gold technique and immunohistochemistry method. RESULTS: A total of 56 F0 mice were obtained, and 2 of them carried homologous recombined HBeAg gene. Six positive F1 mice were obtained, from which 22 homozygous and 29 heterozygous F2 generation HBeAg transgenic mice were obtained. High concentration of HBeAg protein was detected in the peripheral blood of all the positive HBeAg transgenic mice without HBeAb expression. HBeAg expression was detected in the hepatocytes of HBeAg transgenic mice. CONCLUSIONS We obtained a new strain of HBeAg transgenic mice with stable expression of HBeAg in the hepatocytes and immune tolerance to HBeAg using CRISPR/Cas9 technique, which provide a new animal model for studying HBV.
Animals ; CRISPR-Cas Systems ; Female ; Genetic Vectors ; Hepatitis B e Antigens ; genetics ; Hepatitis B virus ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic

To explore the medical students' humanities quality education practice,taking the teaching practice of reading and thinking as an example from the perspective of nationwide reading.The curriculum plan is set up through teaching objectives,teaching content,teaching methods and evaluation of teaching effect.As a general knowledge course for medical students' humanistic education,the reading and thinking could cultivate the concept that "learning to learn" is more important than "learning knowledge" among medical students,so that to enhance the medical students' humanities quality comprehensive level.Medical students' humanistic quality education is of great practical significance,in which the rich teaching contents and diverse teaching methods could stimulate medical students' interest in reading and improve their thinking ability.What's more,the flexible forms of examination is helpful to realize the curriculumgoal.