Objective:To explore any effect of repeated transcranial magnetic stimulation (rTMS) on the upper limb motor function and cerebral cortex activation of stroke survivors.Methods:Sixty stroke survivors were randomly divided into an intervention group and a control group, each of 30. In addition to routine rehabilitation training (including drug therapy, comprehensive hemiplegic limb training and physical factor therapy), the intervention group received 15 minutes of rTMS daily, five days a week for 4 weeks while the control group was given false rTMS. Upper limb motor function was evaluated before and after the treatment using the Fugl Meyer upper limb motor function rating scale (FMA-UE). Functional near-infrared spectroscopy was used to detect and compare the activation (β values) of the prefrontal cortex, the motor cortex and the primary somatosensory cortex in the 2 groups. The correlation between the FMA-UE scores and the β values was quantified.Results:①There was no significant difference in the average FMA-UE scores between the two groups before the treatment. Afterward, though both groups′ average scores had increased significantly, there was significantly greater improvement in the treatment group. ②There was also no significant difference in average β value between the two groups before the experiment, but afterward the average βs of channels 27 and 13 in the intervention group were significantly higher than in the control group. Moreover, in patients with lesion in the left brain, the β-values of CH27 and CH13 were also significantly higher than the control group ( P<0.05). ③The FMA-UE scores of the intervention group were moderately correlated with the CH27 and CH13 β values, but those of the control group were only weakly correlated with the β values of CH27. Conclusion:Transcranial magnetic stimulation activates a lesioned left brain region, improving upper limb motor function. The improvement is correlated with the activation of the left prefrontal cortex and the left primary somatosensory cortex.

Objective Studies on the expression and location of zinc finger protein A20 (A20) and connective tissue growth factor (CTGF) in liver tissues of patients with chronic hepatitis B were conducted, and the relationship between them and liver fibrosis was determined by FibroScan. Methods Studies on A20 and CTGF in liver tissues of 160 patients with chronic hepatitis B were conducted in accordance with the stage of pathological fibrosis and inflammation of the liver, and quantitative immunohistochemistry test was conducted, and statistical analysis was conducted by FibroScan. Results The expressions of A20 and CTGF in liver tissues increased with the aggravation of liver pathological fibrosis and inflammation, and there were significant differences between each stage and the control group (P<0.05), and there were significant differences between adjacent groups (P<0.05). Studies have shown that FibroScan increases along with pathological fibrosis and inflammation in the liver. There are significant differences between the stage and the control group (P<0.05), and no significant differences between the adjacent groups (P>0.05). There was positive correlation between liver A20 and CTGF, r=0.796 (P<0.05). Conclusions In patients with chronic hepatitis B, A20, CTGF and FibroScan are positively correlated with the degree of liver fibrosis, and A20 and CTGF are also positively correlated with the degree of liver inflammation, which can be used as indicators to evaluate the degree of liver inflammation and fibrosis, and further guide the anti-inflammatory and anti-fibrosis treatment of patients.

Vaccines are among the most effec-tive measures for preventing infectious diseases and play a crucial role in controlling the spread of these diseases.Adjuvants,serving as auxiliary com-ponents in vaccines,are indispensable in the vac-cine development process.Ideal adjuvants not only enhance the immune response,enabling the body to achieve optimal protective immunity but also play important roles in reducing the dosage of im-munogens and lowering vaccine production costs.To meet the demands of novel vaccines,many new types of adjuvants have been developed.However,there is still a lack of adjuvants that are safe,effec-tive,easy to prepare,highly pure,and suitable for a variety of vaccines in clinical settings.This article categorizes adjuvants and summarizes their mecha-nisms of action and characteristics,focusing on tra-ditional aluminum salt adjuvants and more modern lipid-based and nucleic acid-based adjuvants.The summary is based on a computer search of data-bases including PubMed,Embase,The Cochrane Li-brary,CNKI(China National Knowledge Infrastruc-ture),VIP Database,and Wanfang Database,using English search keywords such as Adjuvants,Vac-cine,Vaccine Adjuvant,aluminum salts,MF59,AS03,Toll-like receptor agonist,etc.,and corre-sponding Chinese search terms.The aim is to pro-vide references for the development and applica-tion of adjuvants.

Familial primary nocturnal enuresis (FPNE) is common in clinical practice and has shown an obvious familial aggregation that is associated with genetic factors.It has been found that chromosomes 4, 8, 12, 13 and 22 are related to the inheritance of enuresis. PRDM13 and EDNRB genes are related to the pathogenesis of enuresis, but the specific functions remain unclear.FPNE accounts for a high proportion in patients with refractory enuresis.Compared with other types of primary enuresis, FPNE is not difficult to be diagnosed, as long as the related family members have enuresis, it can be diagnosed as FPNE.Due to treatment difficulties, FPNE easily lasts into adulthood, serving as a type of intractable enuresis.Therefore, early diagnosis and active intervention should be made for children with FPNE.In this review, the epidemiology, pathogenesis, diagnosis and treatment of FPNE were summarized, aiming to provide references for improving the clinical diagnosis and treatment of FPNE.

OBJECTIVE: To observe the effects of probiotics supplementation on the natural killer T cell (NKT cell) and inflammatory factors in children with sepsis and its protective effect on long-term lung function. METHODS: A total of 100 children with sepsis admitted to the department of pediatric intensive care unit (PICU) of Henan Provincial People's Hospital from March 2021 to May 2022 were selected as the research objects. The children were randomly divided into placebo group and probiotic group, 50 cases in each group. In addition to the conventional treatment, the probiotic group was given oral or nasal administration of 0.5 g probiotics, three times a day for 30 days, and the placebo group received oral placebo. 40 healthy children were selected as the healthy control group. The levels of interleukins (IL-4, IL-10), interferon-γ (IFN-γ) and immunoglobulin E (IgE), percentages of NKT cell in blood and induced sputum, lung function of the two groups of children with sepsis were measured before treatment, 7 days after treatment, and during follow-up. All these data were compared with those of healthy children. Kaplan-Meier analysis was used to compare the incidence of cough varied cough (CVA) between the two septic groups. Multiple linear regression analysis was used to explore the influence of various factors on the proportion of NKT cells in induced sputum. RESULTS: In the placebo group, 2 cases died and 4 cases were lost to follow-up. In the probiotics group, 3 cases died and 5 cases were lost to follow-up. All the inflammatory factors of two groups decreased slowly after 7 day after treatment. There was no significance in the parameters of the two groups, but the levels of probiotic group declined more evidently. During the follow-up, a further decrease of inflammatory factors in probiotic group could be found, the levels of IL-4 and IL-10 were significantly different from those in the placebo group [IL-4 (ng/L): 20.3±9.3 vs. 27.6±11.9, IL-10 (ng/L): 23.1±6.8 vs. 14.4±4.4, both P < 0.05], with a significant decrease in IgE level (μg/L: 53.0±15.6 vs. 64.2±16.9, P < 0.05]. The results of flow cytometry showed that the percentage of NKT cell in peripheral blood in two septic groups decreased gradually, and the proportion of peripheral blood NKT cells in the probiotics group was significantly lower than that in the placebo group after 7 days of treatment [(4.2±0.9)% vs. (5.3±1.2)%, P < 0.05]. In the follow-up, the level of NKT cell in peripheral blood and induced sputum in probiotic group were lower than the placebo group [peripheral blood: (0.024±0.009)% vs. (0.029±0.008)%, induced sputum: (0.025±0.008)% vs. (0.035±0.01)%, both P < 0.05], which were similar to those in the healthy control group. Meanwhile, the percentage of predicted peak expiratory (PEF%) and ratio of forced expiratory volume in one second/forced vital capacity (FEV1/FVC) of probiotic group were higher than those in the placebo group [PEF%: (91.3±4.8)% vs. (85.8±8.6)%, FEV1/FVC ratio: (91.8±4.7)% vs. (87.2±7.4)%, both P < 0.05]. Although there was no significance in the incidence of CVA between two septic groups according to the Kaplan-Meier curve analysis, multiple linear regression analysis showed mechanical ventilation and allergic history were the risk factors for the increase of NKT cells [β values were 0.584, 0.601, 95% confidence interval (95%CI) were 0.069 to 1.099, 0.011 to 1.192, P = 0.027, 0.046], and probiotics was an independent protective factor for the relieve of increase in NKT cells (β value was -0.984,95%CI was -1.378 to -0.591, P = 0.001). CONCLUSIONS Application of probiotics to septic children early could promote the recovery of NKT cell and inflammatory factors, and alleviate the lung function injury induced by them during follow-up, which is helpful to improve the long-term prognosis of the patients.
Child ; Humans ; Interleukin-10 ; Interleukin-4 ; Sepsis ; Probiotics/therapeutic use* ; Lung ; Cough ; Immunoglobulin E

Anorectal malformation (ARM) accounts for the first place of digestive tract malformations in children, with the incidence of 1/5 000-1/1 500 in newborns.ARM is typically manifested as anal stenosis or anal atresia with or without fistulas and persistent cloaca.Genitourinary malformation is the most common malformation associated with ARM, with the incidence ranging 26%-55%.There were 35%-50% of ARM children develop spinal cord peripheral abnormalities or neurogenic lower urinary tract dysfunction, which usually causes voiding dysfunction associated with ARM.Urodynamic study is the best method to analyze the changes of lower urinary tract function, which can provide an objective classification for bladder and urethral function and guide the formulation of precision treatment plan and therapeutic efficacy during the follow-up period.This study aims to review the cause of voiding dysfunction asso-ciated with ARM and its urodynamic changes.

The important function of the endplate is to transmit stress and supply nutrition. Endplate degeneration might induce or promote degeneration of the intervertebral disc, causing a series of spine diseases that seriously impair people’s health and life quality. Endplate chondrocytes can respond to mechanical stimulation, which is an important factor affecting endplate degeneration. Inappropriate mechanical stimulation will accelerate endplate degeneration. This review summarized the effects of mechanical stimulation on vertebral endplate chondrocyte apoptosis, synthesis inhibition, calcification, and extracellular matrix degradation. The endplate degeneration induced by mechanical stimulation is regulated by a complex network of signal pathways composed of various signal transduction factors. The signal pathways involved in this review included NF-κB, Wnt, Hedgehog, MAPK, RhoA/Rock-1, AKT/mTOR, TGF-β signaling pathway and miRNA related signals. The interconnection of these pathways was highlighted and summarized. Multiple signaling pathways work together to regulate endplate chondrocyte metabolism, which ultimately leads to the endplate degeneration. This review might shed light on early diagnosis and precise treatment of cartilage endplate degeneration.

Objectives:To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention.Methods:Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test.Results:Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ 2=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ 2=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ 2=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ 2=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions:The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.

Objective: The aim of the present study was to investigate the survival rate and its prognostic factors for patients with biliary tract cancer, and then a prognostic risk prediction model was constructed to predict the survival probability of patients. Methods: A total of 14 005 patients with biliary tract cancer (including gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer), who were diagnosed between 2010 and 2015 in the US National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER) were included in the development cohort. The prognostic risk factors of biliary tract cancer were investigated using multivariate Cox regression models. The predictive nomograms were then constructed to predict the overall survival probability of 1, 3, and 5 years, and the predictive discrimination and calibration ability of the nomograms were further evaluated. Meanwhile, 11 953 patients who were diagnosed during 2004 to 2009 from SEER Program were then selected to validate the external predictive accuracy of the prediction models. Results: The 1, 3 and 5-year cumulative survival rates of patients with biliary tract cancer were 41.9%, 20.4% and 15.3%, respectively, in the development cohort. Age greater than 50 years, African Americans and Native Americans and Alaska Natives, higher T, N and M stage and poor histological differentiation grade were risk factors for death, while married status, Asia-Pacific Islanders, insured status and surgery on primary site were protective factors. Gender was not significantly associated with the overall survival. The C statistic of the prediction model was 0.73 (95%CI: 0.72-0.74), and the calibration curve showed that the interaction curves of predictive and actual survival rates of 1, 3 and 5 years were close to the 45 degree diagonal. Results in the validation cohort were similar with those in the construction cohort, with a C statistic of 0.70 (95%CI: 0.69-0.72), indicating high external applicability of the prediction model. Findings from gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer are in consistent with the overall biliary tract cancer. Conclusions The survival rate of patients with biliary tract cancer is relatively poor, and the survival prediction model based on prognostic factors has high prediction accuracy. In the future, this prognostic prediction model could be applied to clinical practice to guide individualized treatment for patients with biliary tract cancer.

Objective To investigate the expressions of miR-21 in clinical lung tissues,serum of lung cancer patients and X-ray irradiated A549 cells in vitro and in vivo.Methods A549 cells were irradiated with 2 and 4 Gy X-rays,and pulmonary metastasis model of lung cancer in nude mice was established to detect the expression of miR-21 in vitro and in vivo,as well as in clinical lung tissues of different pathological types serum sample of lung cancer patients and NSCLC patients whether or not received radiotherapy.The survival rate was further analyzed in the above mention NSCLC patients.Results The miR-21 expressions was up-regulated in 60.0％ of tissue samples of NSCLC patients,and it was up-regulated in 50.5％ serum samples of lung cancer patients (52 out of 103).The miR-21 expressions in lung adenocarcinoma and squamous cell carcinoma had significant difference (x2 =5.766,P ＜ 0.05).In the serum samples of 87 NSCLC patients,miR-21 was detected in 66.7％ samples from the patients of radiotherapy but only 39.6％ of patients without radiotherapy (x2 =6.321,P ＜ 0.05).Kaplan-Meier curves showed that the survival rate of patients with low miR-21 expression was higher than that with high miR-21 expression (P ＜ 0.05).Multivariate Cox regression analysis demonstrated that the miR-21 expression,regional lymph node metastasis and radiotherapy were independent prognostic factors for NSCLC patients.The expression of miR-21 was up-regulated significantly in X-ray irradiated A549 cells at different time-points after irradiation (t =-7.552--1.206,P ＜ 0.05).Furthermore,the expression of miR-21was up-regulated in the serum and lung of nude mice (t =-47.845--2.356,P ＜ 0.05).Conclusions The X-ray irradiation could up-regulate the expression of miR-21 in A549 cells in vitro and in vivo,which might be correlated with the enhanced metastasis of A549 cells.