Objective:To report the clinical characteristics of a case of childhood amyotrophic lateral sclerosis (ALS) caused by SPTLC2 c.778G>A (p.Glu260Lys) mutation. Methods:Whole exon sequencing or whole genome sequencing data from 1 936 patients in the ALS cohort of Peking Union Medical College Hospital were screened for SPTLC2 gene mutations. Clinical data, laboratory examination, neurophysiological examination and genetic test results of the proband were collected. Results:Only one 9-year-old male child with SPLTC2 gene mutation was found. He was admitted to the Department of Neurology, Peking Union Medical College Hospital in December 2022 due to"progressive limb weakness for more than 4 years". Physical examination revealed atrophy and fasciculations of the tongue. Weakness of 4 limbs, muscle atrophy, as well as bilateral hyperreflexia, clonus, and Babinski sign were present. Whole genome sequencing indicated that SPTLC2 gene had c.778G>A (p.Glu260Lys) missense mutation, and no other pathogenic mutations of ALS related genes were detected. Sanger sequencing and family verification showed that neither father nor mother carried the mutation, suggesting that it was a de novo mutation. Nerve conduction velocity test showed no abnormalities, and electromyography suggested neurogenic lesions. Neurofilament light chain in cerebrospinal fluid and serum were increased significantly. The patient′s symptoms continued worsening even after oral administration of L-serine. Conclusion:SPTLC2 gene mutation can cause childhood ALS, and further study of its potential pathogenesis is helpful to uncover another potential pathway of ALS and a novel therapeutic target.

Objective:To construct standard strains representing the main epidemic clades of HIV-1 in China, amplify the virus strains, and establish a seed lot.Methods:Six isolates of HIV-1 virus were identified and analyzed in genotype and phenotype, according to " interpretation for the social organization of the Standard strains of pathogenic microorganism- technical specifications for establishment of HIV strains". The isolates were amplified and cultivated to generate the secondary generation primary seed lot and the third generation working seed lot as frozen storage in liquid nitrogen. Results:Six HIV-1 standard strains were obtained, of which 3 strains are CRF_ 07BC (NRPC2.4.9003, NRPC2.4.9005, NRPC2.4.9006), 1 strain is CRF_ 01AE (NRPC2.4.9001), 1 strain is CRF_ 08BC (NRPC2.4.9002), and 1 strain is URF (NRPC2.4.9004). Phenotypic detection showed that all six strains are CCR5 tropics and Non syncytia inducing virus. TCID 50 were all greater than 1 × 10 5/ml, and concentrations of p24 antigen were all higher than 2 ng/ml. A primary seed lot with no less than 20 vials per strain and a working seed lot with no less than 50 vials per strain were constructed. The standard virus strains were used in evaluating antiviral drugs PEG2kC34, PEG5kC34, LP-19, and neutralizing antibody LSEVh LS-F. Conclusions:Six standard strains of HIV-1 virus covering the three main epidemic subtypes of HIV-1 in China have been obtained, and a storage of HIV-1 standard strain was constructed. It meets the need of the preservation of HIV-1 standard strains in China and provides support for drug and vaccine evaluation.

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Objective:To investigate the etiology of bilateral cerebral infarction (BCI) and influencing factors of short-term clinical outcome.Methods:Patients with BCI admitted to the Department of Neurology, Xiangyang Central Hospital from January to July 2020 were enrolled retrospectively. According to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria, the etiological classification was performed, including large artery atherosclerosis (LAA), cardioembolism (CE), small vessel occlusion (SVO), stroke of other determined etiology (SOE), and stroke of undetermined etiology (SUE). According to the location of acute infarction showed on diffusion-weighted imaging, the patients were divided into anterior circulation group, posterior circulation group, and anterior + posterior circulation group. The demographic and baseline data of the three groups were compared. The short-term outcome was assessed by the modified Rankin Scale score at discharge. 0-2 was defined as good outcome, and >2 were defined as poor outcome. The clinical data of the good outcome group and the poor outcome group were compared. Multivariate logistic regression was used to analyze the independent influencing factor of short-term clinical outcome. Results:A total of 72 patients with BCI were enrolled, accounting for 9.4% of all acute cerebral infarction. Their age was 67.89±12.50 years. There were 41 males (56.9%). Twenty-three patient were in the anterior circulation group (32.0%), 25 were in the posterior circulation group (34.7%), and 24 were in the anterior + posterior circulation group (33.3%). The etiological types were SUE in 25 cases (34.7%), CE in 22 cases (30.6%), LAA in 14 cases (19.4%), SOE in 9 cases (12.5%), and SVO in 2 cases (2.8%). CE, SUE and SOE were the main etiologies in the anterior circulation group, and CE was the most common (43.5%). The proportion of CE was significantly higher than that in the posterior circulation group ( P=0.036), and there was no significant difference compared with the anterior + posterior circulation group. LAA, SUE and CE were the main etiologies in the posterior circulation group, and LAA was the most common (48.0%). The proportion of LAA was significantly higher than that in the anterior circulation group ( P<0.001) and the anterior + posterior circulation group ( P=0.002). SUE, CE and SOE were the main etiologies in the anterior + posterior circulation group, and SUE was most common (37.5%). However, there was no significant difference in the proportion of SUE between the anterior + posterior circulation group, the anterior circulation group and the posterior circulation group. Forty patients (55.6%) had poor short-term outcomes. The history of ischemic heart disease, fasting blood glucose, baseline National Institutes of Health Stroke Scale (NIHSS) score, large infarction (the largest infarct diameter >5 cm), the number of infarct distribution layers (6.6 mm/layer) and the proportion of LAA in the poor outcome group were significantly higher than those in the good outcome group (all P<0.05). Multivariate logistic analysis showed that higher baseline NIHSS score was an independent risk factor for poor outcome in patients with BCI (odds ratio 1.373, 95% confidence interval 1.014-1.859; P=0.041). Conclusions:BCI is not uncommon. Its main etiologies are SUE, CE and LAA. CE is the most common in the anterior circulation BCI, LAA is the most common in the posterior circulation BCI, and SUE is the most common in the anterior + posterior circulation BCI. The short-term poor outcome rate of BCI is higher, and the higher baseline NIHSS score is an independent risk factor for poor outcome of patients with BCI.

It has been a hundred years since the first case of spinal muscular atrophy(SMA) was reported in the medical literature. In its 100 years of history, medical development for the cure of SMA has gone through many stages, from clinical manifestation description, accumulation of cases, disease classification exploration to pathogenic gene mapping and cloning, clinical application of gene diagnosis, animal model establishment then to R&D of disease modifying drugs and clinical use of novel therapies. The future of the development lies in breakthrough in pathophysiological mechanism, carrier screening and precise prevention, as well as new therapies. As a representative of monogenic rare diseases, review the history of the progress in diagnosis and treatment and R&D in medications and discuss the prospect of further development in the future is instrumental in leading the continued advancement of the whole cause of rare disease.

Objective:To analyze the characteristics of viral isolation and unique recombinant from untreated HIV-1 patients infected through sexual transmission and injection drug use, so as to provide evidence for understanding the biological characteristics and precise prevention and control of HIV-1 infection in different transmission routes.Methods:In view of the different HIV-1 transmission risks, newly diagnosed untreated HIV-1 patients from Beijing, Guangxi and Sichuan were carefully selected. Venous blood was collected to detect the viral load and CD4 + T cell count, and peripheral blood lymphocytes were isolated for virus isolation. Viral RNAs were extracted from the virus supernatant, and the near full-length genome sequences were obtained using in-house method, then the recombination patterns were determined. Results:Among the 65 HIV-1 infection, 32(49.2%), 20(30.8%) and 13(20.0%) were infected via men who have sex with men (MSM), heterosexual and injection drug use (IDU), respectively; genotypes mainly included 26(40.0%) CRF07_ BC, 23(35.4%) CRF01_ AE, and 9(13.8%) unique recombinant types (URFs). A total of 46 HIV-1 clinical strains were isolated. The positive rate of HIV-1 isolation was significantly negatively correlated with CD4 + T cells ( X2=4.22, P=0.04), but positively correlated with viral load ( X2=22.4, P<0.001); the multi-variate generalized estimating equations(GEE) model analysis of HIV-1 P24 antigen content showed similar result. In addition, GEE model showed a positive correlation between viral P24 antigen content and virus-producing culture time (52.14, 95% CI: 9.42~94.87, P=0.017). Viral growth curve analysis showed that the level of viral P24 antigen in MSM Group was significantly higher than that in heterosexual group and IDU group (adjusted P values were p<0.01 and P<0.05, respectively), on the 14th day after culture. The proportion of URFs in MSM Group was higher than that in heterosexual group, and the recombinant breakpoints in MSM Group were more than that in heterosexual group. Conclusions:MSM population was more sensitive to HIV-1 virus isolation; there was unique diversity of recombinant forms of HIV-1 among those with sexually transmitted infections, especially in the MSM population.

Objective:To analyze the epidemiological characteristics of untreated 16-25 years old people living with HIV-1 (PLWH) in Dehong on the China-Myanmar border during 2009 to 2017, by using molecular network method and to provide references for precise prevention and reduction of the spread of HIV-1 in Dehong.Methods:Screening people living with HIV-1, collecting blood sample and separating plasma, extracting RNA were performed to amplify HIV-1 pol sequence, construct molecular network by HIV-TRACE program and conduct statistical analysis. Results:Among the 573 infected persons in the group, 319 were Chinese (55.67%), 254 were Burmese (44.33%); 351 were males (61%), and 222 were females (39%); 404 had heterosexual transmission (HET, 70.51%), 110 people injected drugs (PWID, 19.20%), 51 men had sex with men (MSM, 8.9%); genotypes included 252 unique recombinant forms (43.98%), and 222 had circular recombinant forms (39.02%), 76 had HIV-1 C (13.26%) and 23 HIV-1 B (4.01%) infection. The 83 molecular networks constructed through HIV-TRACE involved 250 PLWH, 49% were the China-Myanmar mixed network (41/83). Myanmar citizens were at high risk of accessing the China-Myanmar mixed network ( AOR=2.676, p=0.002). Chinese male PWID network assortativity is 0.34, Myanmar male PWID was 0.14, MSM was 0.12. Conclusions:There is a continuous risk of cross-border transmission of HIV-1 in Dehong on the China-Myanmar border; attention should be paid to the mixed transmission of MSM and Myanmar male PWID populations with other transmission routes.

It is reported that a patient who committed suicide by oral hydrochloric acid was misdiagnosed as "dichlorvos poisoning". The original pesticide bottle was tested to be strong acid, and the nursing process was finally successful. The focus of care includes: Do a good job of emergency care for tracheal intubation and digestive tract, oral care for infection prevention and nutritional support in the advanced stage of the disease, prevention of venous thrombosis in the lower limbs, psychological care during the rehabilitation period, and continued care after discharge.

It is reported that a patient who committed suicide by oral hydrochloric acid was misdiagnosed as "dichlorvos poisoning". The original pesticide bottle was tested to be strong acid, and the nursing process was finally successful. The focus of care includes: Do a good job of emergency care for tracheal intubation and digestive tract, oral care for infection prevention and nutritional support in the advanced stage of the disease, prevention of venous thrombosis in the lower limbs, psychological care during the rehabilitation period, and continued care after discharge.