Background Varicella-zoster virus (VZV) can cause acute brain infection manifesting as meningitis or encephalitis, which more likely occurs in winter and population with immunocompromised conditions[1]. During the enterovirus epidemic season, VZV meningitis is easy to be ignored and misdiagnosed, especially when the typical dermatomal rash is absent. Case presentation Here, we present an atypical case of a young immunocompetent male with VZV meningitis and encephalitis during summer. The patient presented with fever, headache and vomiting, but without dermatomal rash. Metagenomic Next-generation Sequencing (mNGS) of cerebrospinal fluid (CSF) revealed VZV infection. He was treated successfully with acyclovir and recovered without any neurological sign. Conclusions This case report describes a patient with mild diabetes but no immunocompromised condition who developed meningitis and encephalitis resulting from VZV infection in summer. Additionally, there is no dermatomal rash in the patient. It can broaden the understanding of the disease, and keep VZV infection in differential diagnoses of viral meningitis.

Zinc is essential for normal growth and reproduction in all animals and plays a crucial role in many biological processes. The present study aimed to compare the intervention effects of zinc on intestinal health in a high lipid diet or high starch diet. Seven iso-nitrogenous (similar to 520 g kg(-1)) diets were formulated containing a positive control diet (115 g kg(-1) lipid + 115 g kg(-1) starch + 20 mg kg(-1) Zn), three high starch diets (HS, 166 g kg(-1) starch) and three high lipid diets (HL, 182 g kg(-1) lipid), with 0 (HS-LZn, HL-LZn), 20 (HS-MZn, HL-MZn) and 150 (HS-HZn, HL-HZn) mg kg(-1) Zn being supplemented. High starch diet and high lipid diet promoted feed efficiency, as evidenced by the lower feed conversion ratio. Three-way factorial ANOVA analysis showed high starch diet (166 g kg(-1)) significantly decreased final body weight and weight gain compared to the normal starch level (115 g kg(-1)). Diamine oxidase in serum significantly increased in diets HS-LZn and HL-LZn. In addition, distal intestinal mucosal fold damage and inflammatory infiltration were observed in the HS-LZn, HS-HZn, HL-LZn and HL-HZn groups. Fish fed HL diets (HL-LZn, HL-MZn, HL-HZn) showed lower expressions of claudin 5 and claudin 34, and higher IgD and IgM. Diets HL-LZn and HL-MZn significantly up-regulated C4 and C7. Proinflammatory cytokines including il8, il1 beta and tnf alpha significantly up-regulated in diet HL-LZn, even higher than the HS-LZn. Intestinal microbial composition indicated the abundance of Cetobacterium in HL-LZn was significantly higher than the control and HL-MZn diets. Similarly, LEfSe showed that Cetobacterium (P = 0.039) significantly enriched in the HL-LZn group. This study clarified high energy diet induced intestinal damage, which can be alleviated by zinc.

The outcome of weight loss surgery is related to several factors, and for super-obese patients, the rate of weight loss failure and weight recovery after Roux-en-Y gastric bypass (RYGB) is high. Relevant studies have shown that the weight loss effect also correlates with total small bowel length (TSBL) and biliopancreatic (BP) and Roux limbs. However, there are few studies on the relationship between TSBL and anthropometric parameters, the BP limb, the Roux limb, and weight loss effect, and no relevant reports have been reported in China. The objective was to study the relationship between the total length of the small intestine and anthropometric parameters in the Chinese population. The effect of the Roux limb/biliopancreatic limb (RL/BPL) ratio on weight loss and diabetes remission in RYGB patients 1 year after surgery was evaluated to find the appropriate ratio relationship. In this prospective study, 148 patients between the ages of 19 and 68 years who underwent laparoscopic Roux-en-Y gastric bypass were enrolled. Height, weight, BMI, the BP limb, the Roux limb, fasting blood glucose (FBG), etc., were noted. To explore the correlation between the total length of the small intestine and these values. Subsequently, the 148 patients were followed up for 1 year after surgery. The patients diagnosed with T2DM before surgery were screened out, and 56 patients were finally identified according to the postoperative follow-up, in which BPL = 50 cm and RL = 150 cm, 175 cm, and 200 cm, respectively. RL/BPL was divided into 3, 3.5, and 4 groups according to the proportional relationship to explore the relationship between RL/BPL and diabetes remission and weight loss. (1) The study included 148 patients (61 women and 87 men). The mean age was 35.68 ± 10.46 years, weight = 127.46 ± 34.51 kg, height = 167.83 ± 9.16 cm, BMI = 44.94 ± 10.58 kg/m2. The average TSBL value was 714.41 ± 101.08 cm. Linear regression analysis showed that TSBL was positively correlated with height, weight, neck circumference, chest circumference, waist circumference, and Roux limb. (2) Fifty-six patients with T2DM who were followed up 1 year after surgery were divided into three groups. Group 1: BPL = 50 cm, RL = 150 cm (n = 20); group 2: BPL = 50 cm, RL = 175 cm (n = 26); group 3: BPL = 50 cm, RL = 200 cm (n = 10); RL/BPL = 3 was associated with higher weight loss than the other groups. The remission rate of diabetes did not differ between the three groups. TSBL was positively correlated with height, weight, neck circumference, chest circumference, waist circumference, and Roux limb. The TSBL of males was significantly higher than that of females. Among patients with T2DM who participated in the follow-up 1 year after surgery, RL/BPL = 3 (n = 20) had greater weight loss than the other groups.

Objective To investigate the clinical characteristics of patients with cryptococcal meningoencephalitis with unstable gait as the initial symptom. Methods The clinical datas of a cryptococcal meningoencephalitis patient with unstable gait as the initial symptom were analyzed.Results A 45-year-old male presented with unstable gait two years ago, and the symptoms worsened progressively, complicated with decreased memory and delayed response. Brain MR scans showed dilation of the ventricular system, and cerebrospinal fluid examination revealed cryptococcal infection. After treatment with amphotericin B and fluorocytosine, the clinical symptoms improved. Conclusion Cryptococcal meningoencephalitis usually has an insidious onset, and unstable gait may be the initial symptom, which should be paid attention in clinical practice.

Wernicke's encephalopathy (WE) is a severe neuropsychiatric disorder, mainly resulting from a nutritional deficiency of thiamine. WE is hard to detect at an early stage. Less than 20% of WE can be diagnosed during a patient’s lifetime, and WE tends to occur in patients with chronic alcoholism. Therefore, a large proportion of non-alcoholic WE patients are misdiagnosed. Lactate is an important by-product of anaerobic metabolism when the aerobic metabolism is blocked without thiamine, which can potentially serve as an alerting index for WE. Here, we report a case of a patient with WE who suffered gastric outlet obstruction following postoperative fasting, accompanied by lactic acidosis and refractory thrombocytopenia. A 67-year-old non-alcoholic woman who suffered hyperemesis for 2 months was diagnosed with gastric outlet obstruction (GOO). Gastric biopsies with endoscopy revealed gastric cancer, and total gastrectomy, together with D2 nodal dissection, was performed. She developed a coma with refractory thrombocytopenia rapidly after the surgical procedures were performed. The above conditions were treated not by the administration of antibiotics but by that of thiamine. We also found before the start of the procedures that she had a high level of blood lactate for a long period of time. Early diagnosis of WE is important because permanent injury can be caused to the central nervous system. Even today, the diagnosis of WE mainly depends on clinical symptoms, but occasionally, a typical triad occurs among WE patients. Therefore, a sensitive index for early diagnosis is critical for WE. Rising levels of blood lactate as a result of thiamine deficiency can serve as a warning for WE. In addition, we noted that this patient had a non-typical thiamine-sensitive refractory thrombocytopenia.

Background Duchenne muscular dystrophy (DMD) is an X-linked lethal genetic disorder for which there is no effective treatment. Previous studies have shown that stem cell transplantation into mdx mice can promote muscle regeneration and improve muscle function, however, the specific molecular mechanisms remain unclear. DMD suffers varying degrees of hypoxic damage during disease progression. This study aimed to investigate whether induced pluripotent stem cells (iPSCs) have protective effects against hypoxia-induced skeletal muscle injury. Results In this study, we co-cultured iPSCs with C2C12 myoblasts using a Transwell nested system and placed them in a DG250 anaerobic workstation for oxygen deprivation for 24 h. We found that iPSCs reduced the levels of lactate dehydrogenase and reactive oxygen species and downregulated the mRNA and protein levels of BAX/BCL2 and LC3II/LC3I in hypoxia-induced C2C12 myoblasts. Meanwhile, iPSCs decreased the mRNA and protein levels of atrogin-1 and MuRF-1 and increased myotube width. Furthermore, iPSCs downregulated the phosphorylation of AMPKα and ULK1 in C2C12 myotubes exposed to hypoxic damage. Conclusions Our study showed that iPSCs enhanced the resistance of C2C12 myoblasts to hypoxia and inhibited apoptosis and autophagy in the presence of oxidative stress. Further, iPSCs improved hypoxia-induced autophagy and atrophy of C2C12 myotubes through the AMPK/ULK1 pathway. This study may provide a new theoretical basis for the treatment of muscular dystrophy in stem cells.

TBX1 is systematically conserved in the T-box transcription factor family and regulates craniofacial muscle development during various stages of myogenesis, including commitment, proliferation, terminal differentiation, and survival. However, the role and mechanism by which TBX1 regulates the myogenic development of myoblasts remains unclear. In our study, we overexpressed TBX1 in mouse C2C12 myoblasts using a lentivirus method. We found that TBX1 inhibited cell proliferation and muscle differentiation, which had no effect on apoptosis. During myogenic differentiation, we also found that TBX1 overexpressing cells regulate myogenic differentiation by upregulating the expression levels of Smad2 and Smad3 and downregulating the expression level of MEF2C. After treatment with a specific inhibitor of Smad3 (SIS3), the myogenic differentiation of wild-type and TBX1 overexpressing cells increased. Thus, TBX1 may regulate myoblast muscle differentiation by enhancing the expression of Smad2 and Smad3. TBX1 may be a therapeutic target for muscular dystrophy.

目的 系统评价银杏内酯注射液联合阿替普酶治疗急性缺血性卒中(AIS)的疗效与安全性.方法 采用Cochrane系统评价方法,检索中国期刊全文数据库、万方数据库、维普中文科技期刊全文数据库、中国生物医学文献数据库、中国硕士和博士论文全文数据库、Clinical Trials.gov、PubMed、Embase、The Cochrane Library和Web of Science等数据库,截止日期为2020年7月.筛选关于银杏内酯注射液联合阿替普酶治疗AIS的随机对照试验(RCT)文献.由两名评价员对所有纳入临床研究独立进行数据分析提取及质量评价,采用revman5.3软件进行Meta分析.结果 共纳入9项RCT、765例AIS患者,全部为中文文献.Meta分析结果显示,与阿替普酶治疗比较,银杏内酯类注射液联合阿替普酶治疗显著改善AIS患者神经功能缺损(MD=-3.08,95％CI:-3.74～-2.43,P<0.00001),临床有效率显著提高(OR=3.93,95％CI:2.37～6.52,P<0.00001),患者生活质量(MD=7.06,95％CI:3.71～10.40,P<0.0001)及Barthel指数显著改善(MD=8.96,95％CI:6.00～11.92,P<0.00001),而不良反应发生率比较差异无统计学意义(OR=0.76,95％CI:0.42～1.40,P=0.38).结论 银杏内酯注射液联合阿替普酶治疗AIS患者可显著改善神经功能缺损,提高临床疗效和患者生活质量,但仍需要更多大样本、多中心、高质量研究证实.

Duchenne型肌营养不良症(Duchenne muscular dystrophy,DMD)是一种X连锁致死性遗传性肌病,由Dystrophin基因突变导致抗肌萎缩蛋白缺失所致.DMD尚缺乏有效的治疗方法,但随着对该病发病机制和病理变化过程的认识不断深入,其治疗选择越来越多.这些治疗方法旨在恢复Dystrophin蛋白表达或弥补Dystrophin蛋白缺失.

肥厚性硬脑膜炎(HCP)是一种硬脑膜的局部或弥漫性增厚,伴有或不伴有相关炎症的临床疾病.HCP发病率较低,临床表现多样,临床诊断难度较大.本文报道了2例以反复发作性头痛为临床特征,其中1例出现了视神经损害,经激素治疗后头痛明显好转,结合文献复习,对该病进行讨论.

Background: Duchenne muscular dystrophy (DMD) is a fatal, X-linked recessive muscle disorder characterized by heterogeneous progression and severity. We aimed to study the effects of single nucleotide polymorphisms (SNPs) in SPP1 and LTBP4 on DMD progression in Chinese patients.Methods: We genotyped LTBP4 haplotypes and the SPP1 promoter SNPs rs28357094, rs11730582, and rs17524488 in 326 patients registered in the neuromuscular database of The First Affiliated Hospital of Sun Yat-sen University. Kaplan-Meier curves and log-rank tests were used to estimate and compare median age at loss of ambulation, while Cox proportional hazard regression models were used as to analyze the effects of glucocorticoids treatments, DMD genotype, and SPP1/LTBP4 SNPs on loss of ambulation.Results: The CC/CT genotype at rs11730582 was associated with a 1.33-year delay in ambulation loss (p = 0.006), with hazard ratio 0.63 (p = 0.008), in patients with truncated DMD genotype and undergoing steroid treatment. On the other hand, rs17524488 in SPP1 and the IAAM/IAAM haplotype in LTBP4 were not associated with time to ambulation loss.Conclusions:SPP1 rs11730582 is a genetic modifier of the long-term effects of steroid treatment in Chinese DMD patients. Thus, any future clinical study in DMD should adjust for glucocorticoids use, DMD genotype, and SPP1 polymorphisms.

Central nervous system aspergillosis (CNS-A) is a rare and fatal fungal infection. Voriconazole is the recommended treatment for CNS-A. The therapeutic effect of voriconazole is good, but its use is limited due to adverse reactions. This case report describes a 37-year-old male patient that had previously been diagnosed with acute lymphoblastic leukaemia. He had received immunosuppressive agents for 1 year following a haematopoietic bone marrow transplant. He presented with a 1-month history of left limb weakness as well as recurrent fever. Brain magnetic resonance imaging showed that he had multiple cerebral infarctions. Subsequently, he was diagnosed with CNS-A by metagenomic next-generation sequencing. Voriconazole was added to his treatment regimen, but it resulted in severe haemorrhagic cystitis and possibly bladder rupture. The dose of voriconazole was adjusted and reparative bladder surgery was undertaken immediately. Eventually, the patient was successfully treated with voriconazole and there was no recurrence of symptoms after 1 year of follow-up. Haemorrhagic cystitis is a rare adverse drug reaction associated with voriconazole use. Based on the experience with this current case, physicians should be aware of urinary tract complications with voriconazole including haemorrhagic cystitis.

Compelling evidence implicates that overexpression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor 1 (FGFR1) in non-small cell lung cancer (NSCLC) drives tumor progression, can serve as prognostic biomarkers or therapeutic targets for NSCLC patients. But at present, we still lack of effective drugs for bFGF. The preparation of monoclonal antibodies against bFGF or to understand its mechanism of action is urgently need. Previously, we used hybridoma technology to produce a murine anti-bFGF monoclonal antibody (E12). However, E12 carries risks of heterogeneity and immunogenicity. In the present work, we produced three humanized variants (H1L1, H2L2 and H3L3) based on E12 by substituting residues in or near the complementarity-determining region (CDR). In addition, we thoroughly explored VH/VL domain combinations to simulate full-length IgG1 antibodies using computational protein design. H3L3 was selected for further study, as it demonstrated the best humanization and strongest affinity for bFGF. Specially, humanization of H3L3's light chain and heavy chain were 100% and 98.89%, respectively. The FGF2 neutralizing effect of H3L3 were confirmed by ELISA. We also found that H3L3 can effectively suppress the growth and angiogenesis of cancer through reduce the phosphorylation of AKT and MAPK. Moreover, H3L3 dramatically reduced tumor size and micro-vessel density in nude mice. Altogether, our study demonstrates that H3L3 exerts anti-tumor effects by impeding NSCLC development.

Stem cell therapy is a promising approach for treating Duchenne muscular dystrophy (DMD); however, its application is hindered by poor cell engraftment. There have been no reports to date describing the efficient generation of myogenic progenitors from adipose-derived stem cells (ADSCs) that can contribute to muscle regeneration. In this study, we examined the in vivo myogenic potential of progenitors differentiated from ADSCs using forskolin, basic fibroblast growth factor, the glycogen synthase kinase 3β inhibitor 6-bromoindirubin-3'-oxime as well as the supernatant of ADSC cultures. The results indicate that a proliferative population of myogenic progenitors can be derived from ADSCs that have characteristics similar to muscle satellite cells and are capable of terminal differentiation into multinucleated myotubes. When transplanted into DMD model mdx mice either by intramuscular injection or systemic delivery, progenitors were successfully engrafted in skeletal muscle for up to 12 weeks, and generated new muscle fibers, restored dystrophin expression and contributed to the satellite cell compartment. These findings highlight the potential application of myogenic progenitors derived from ADSCs to the treatment of muscular dystrophy.