Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective:To investigate the carrier rate and clinical characteristics of epigenetic modification gene mutations (EMMs) among patients with acute myeloid leukemia (AML).Methods:One hundred seventy two patients who were initially diagnosed with AML at the First People′s Hospital of Lianyungang from May 2011 to February 2021 were selected as the study subjects. Next-generation sequencing was carried out to detect variants of 42 myeloid genes among these patients. Clinical and molecular characteristics of patients with EMMs and the effect of demethylation drugs (HMAs) on their survival were analyzed.Results:Among the 172 AML patients, 71 (41.28%) were found to harbor the EMMs, and carrier rates were TET2 (14.53%, 25/172), DNMT3A (11.63%, 20/172), ASXL1 (9.30%, 16/172), IDH2 (9.30%, 16/172), IDH1 (8.14%, 14/172), EZH2 (0.58%, 1/172). Patients with EMMs (+ ) had lower peripheral hemoglobin compared with those with EMMs (-) (72 g/L vs. 88 g/L, Z=-1.985, P<0.05). The proportion of EMMs(+ ) among elderly AML patients was significantly higher than that of young AML patients [71.11% (32/45) vs. 30.70% (39/127), χ2 = 22.38, P < 0.001]. EMMs (+ ) were significantly correlated with NPM1 gene variants ( r=0.413, P < 0.001), while negatively correlated with CEPBA double variants ( r=-0.219, P<0.05). Compared with conventional chemotherapy regimens, HMAs-containing chemotherapy regimens have improved the median progression-free survival (PFS) and median overall survival (OS) among intermediate-risk AML patients with EMMs (+ ) (PFS: 11.5 months vs. 25.5 months, P<0.05; 12.5 months vs. 27 months, P<0.05). Similarly, Compared with conventional chemotherapy regimens, chemotherapy with HMAs had increased median PFS and median OS in elderly AML patients with EMMs(+ ) (4 months vs. 18.5 months, P<0.05; 7 months vs. 23.5 months, P<0.05). Conclusion:Patients with AML have a high rate of EMMs carriage, and HMAs-containing chemotherapy regimens can prolong the survival of elderly patients with AML with poor prognosis, which may provide a reference for individualized treatment.

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Objective:To evaluate the clinical efficacy of the modified biplane Chevron osteotomy and autogenous osteochondral transplantation for the treatment of talar cartilage injury with bone cyst.Methods:From February 2016 to February 2019, 26 patients with talar cartilage injury and bone cyst were treated at Department of Orthopaedics, The First Affiliated Hospital to Guangxi Medical University. They were 16 males and 10 females, aged from 22 to 50 years (average, 36.2 years). According to the Hepple classification, there were 5 cases of type Ⅳ and 21 cases of type Ⅴ. The extent and range of talar cartilage injury were evaluated by arthroscopy, the modified biplane Chevron osteotomy of medial malleolus was performed to expose cartilage defects medial to the talus, unstable cartilage was removed thoroughly, sclerotic wall of the bone cyst was freshly treated, and an osteochondral column taken from the non-weight-bearing area of the ipsilateral femoral medial condyle was implanted into the injured area of talar cartilage. The clinical efficacy was evaluated by comparing the ankle-hindfoot scores of American Orthopedic Foot and Ankle Society (AOFAS), Karlsson ankle scores, visual analogue scale (VAS) and Lysholm ankle scores between preoperation and one year post-operation.Results:All the 26 patients were followed up for an average of 20.6 months (from 12 to 30 months). Follow-up did not observe any postoperative complications like incision infection, cyst recurrence or malunion, or any obvious pain or movement limitation at the donor knee joint. The AOFAS ankle-hindfoot scores were significantly increased from preoperative 64.3±3.9 to 89.5±5.1 one year postoperation, the Karlsson scores were significantly increased from preoperative 60.5±5.5 to 85.2±6.9 one year postoperation, and the VAS scores were significantly decreased from preoperative 6.2±1.1 to 1.8±0.9 one year post-operation (all P<0.05). The Lysholm ankle scores before and after operation were 94.7±1.9 and 94.1±1.8, respectively, showing no significant difference ( P>0.05). Conclusion:In the treatment of talar osteochondral injury and bone cyst, the modified biplane Chevron osteotomy of medial malleolus and autogenous transplantation of osteochondral column can effectively relieve ankle pain and improve ankle function, leading to satisfactory clinical efficacy.

Percutaneous coronary intervention is an extremely effective method for the treatment of acute myocardial infarction.In some patients, allergic reactions to metals such as in-stent restenosis and coronary aneurysm dilatation will occur.Currently, treatment options for such patients remain controversial.Studies have shown that nickel is a common cause of recurrent in-stent restenosis.

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Non-neonatal tetanus remains a serious public health problem, although neonatal tetanus has been eliminated in China since 2012. Non-neonatal tetanus is a potential fatal disease. In the absence of medical intervention, the mortality rate of severe cases is almost 100%. Even with vigorous treatment, the mortality rate remains 30%-50% globally. These specifications aim to regulate non-neonatal tetanus diagnosis and treatment in China, in order to improve medical quality and safety. These specifications introduce the etiology, epidemiology, pathogenesis, clinical manifestations and laboratory tests, diagnosis, differential diagnosis, grading and treatment of non-neonatal tetanus.

Tetanus consists of neonatal tetanus and non-neonatal tetanus.Non-neonatal tetanus remains a serious public health problem,although neonatal tetanus has been eliminated in China since 2012.Non-neonatal tetanus is a potential fatal disease.In the absence of medical intervention,the mortality rate of severe cases is almost 100％.Even with vigorous treatment,the mortality rate is still 30％-50％ globally.These specifications aim to regulate non-neonatal tetanus diagnosis and treatment in China,in order to improve medical quality and safety.These specifications introduce the etiology,epidemiology,pathogenesis,clinical manifestations and laboratory tests,diagnosis,differential diagnosis,grading and treatment of non-neonatal tetanus.

Extensive-stage small cell lung cancer (ES-SCLC) accounts for approximately two-thirds of all SCLCs. Chemotherapy is still the main treatment, supplemented with radiotherapy and other comprehensive treatments. Although sensitive to chemotherapy and radiotherapy, almost all ES-SCLCs are vulnerable to treatment resistance and have high recurrence rates. Therefore, novel therapies are needed to improve treatment efficacy. The recent advances in radiotherapy for ES-SCLC include prophylactic cranial irradiation (PCI) and thoracic radiotherapy (TRT). Moreover, immunotherapy has shown good antitumor activity, and immune-checkpoint inhibi-tors may become an important breakthrough in SCLC treatment. This article briefly reviewed the clinical research on radiotherapy and immunotherapy for advanced-stage SCLC.

Objective To study the effect of astragalus polysaccharides combined with hUSCs transplantation on type 2 diabetic rats. Methods Twenty-five SD rats were randomly selected into the normal control group, and the remaining 105 SD rats were used to establish type 2 diabetes model. The 100 rats successfully modeled were randomly divided into the diabetes group, astragalus polysaccharide treatment group, hUSCs treatment group, and astragalus polysaccharide+hUSCs treatment group, with 25 rats in each group. After 2 weeks of treatment, the FBG concentration, insulin and C-peptide concentrations, and body weight changes were measured in each group. The distribution and survival of PKH-26-labeled hUSCs in rat pancreatic tissue were observed by fluorescence microscopy. TUNEL method was used to detect the apoptosis of rat islet cells. Real-time quantitative PCR and Western Blot were used to detect the expression of TGF-β/Smad signaling pathway-related genes in rat pancreatic tissue. Results The FBG concentration of rats in the astragalus polysaccharide treatment group, hUSCs treatment group and astragalus polysaccharide +hUSCs treatment group were significantly decreased, and that in the combination treatment group was significantly lower those in the astragalus polysaccharide group and hUSCs group, and the differences were statistically significant ( all P<0 . 05 ) . Compared with the diabetic group , the insulin concentration, C-peptide concentration and body weight in the astragalus polysaccharide treatment group, hUSCs treatment group and combination treatment group rats were significantly increased, and those in the combination treatment group was significantly higher than those in the astragalus polysaccharide treatment group and in the hUSCs treatment group, the differences were statistically significant( all P<0.05). The results of fluorescence microscopy showed that the number of PKH-26 positive hUSCs in the combined treatment group was 74.64 ±9.75 in each high power field, which was significantly higher than that in the hUSCs treatment group (43.64±5.83), the difference was statistically significant (P<0.05). Compared with the diabetic group, the apoptotic rates of islet cells in the astragalus polysaccharide treatment group and the hUSCs treatment group were reduced, and the relative expressions levels of mRNA and protein of TGF-β1, Smad3, and Smad7 in the pancreatic tissue were also significantly reduced(all P<0.05). The reduction was more significant in the combination treatment group, and the differences were statistically significant (all P<0.05). Conclusions Astragalus polysaccharide combined with hUSCs transplantation can effectively reduce the FBG concentration, increase the concentration of insulin, C-peptide and body weight, reduce the apoptosis of pancreatic islet tissue, which may be related to the reduction of TGF-β/Smad in pancreatic tissue. Signaling pathways are involved in suppressing the inflammatory response.

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Although neonatal tetanus in China has been eliminated since 2012, non-neonatal tetanus remains a serious public health problem. Non-neonatal tetanus is a potential fatal disease, and the mortality rate of severe cases is almost 100% in the absence of medical intervention. Even with vigorous treatment, the mortality rate is still 30~50% globally. In order to standardize the diagnosis and treatment of non-neonatal tetanus in China, this specification is hereby formulated. This standard includes etiology, epidemiology, pathogenesis, clinical manifestations, laboratory tests, diagnosis, differential diagnosis, classification, grading and treatment of non-neonatal tetanus.