ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

Objective To evaluate the clinical efficacy of plasma exchange(PE)and double plasma molecular absorption system(DPMAS)in the treatment of primary biliary cholangitis(PBC)and the effect of this therapy on prognosis.Methods The clinical data on 526 PBC patients in our hospital from December 2013 to January 2022 were retrospectively analyzed.The patients were divided into different groups according to different therapies and then matched with propensity.The changes in symptoms,laboratory indexes and MELD scores were compared between two groups before and after treatment,and the clinical efficacy of artificial liver treatment for PBC patients was assessed.The effect of this treatment on the survival outcomes in these patients via comparing the cumulative survival rates at 3,6 and 12 months between the two groups.Results The efficiency was better in the group with artificial liver treatment in addition medical therapy than the group with medical treatment alone,the difference was statistically significant(76.7%vs.55.8%,χ2 = 4.214,and P = 0.040).Cox proportional risk regression showed that TBIL was an independent risk factor affecting the 3-,6-,or 12-month survival in PBC patients.Conclusions Artificial liver support system can effectively relieve symptoms,reduce levels of ALT,AST and TBIL,improve blood coagula-tion function,and lower MELD scores in PBC patients.This therapy revealed a trend of improvement in 3-,6-,or 12-month survival outcomes.

Objective Amyotrophic lateral sclerosis(ALS)is a progressive and fatal neurodegenerative disease.Mutations in the Cu/Zn superoxide dismutase 1 gene(SOD1)have been identified as the cause of familial ALS.Sequencing the SOD1 gene may be helpful for patients with a suspected family history of ALS.This article reports for the first time a case of amyotrophic lateral sclerosis with SOD1-p.A5S mutation in Han Chinese and summarizes its clinical characteristics.Method and Results This is the first report on Chinese Han of ALS with SOD1-p.A5S mutation and review of relevant case literature to summarize its clinical characteristics.The study case is a 34-year-old male who was admitted to the Neurology Department of The First Affiliated Hospital of Xi'an Jiaotong University with a complaint of"weakness in both lower limbs for 2 years,worsening with both hands for 6 months".The main clinical manifestations were progressive limb weakness,no swallowing difficulties or cognitive impairment.Further improvement of routine examinations and electromyography after admission were made to rule out other diagnoses,and genetic testing was conducted.Based on the patient's typical clinical manifestations and evidence of involvement of lower motor neurons in the cervical,thoracic,and lumbar spinal cord areas indicated by electromyography,other diagnoses and characteristic gene testing results were reasonably excluded,and ALS was diagnosed.The genetic testing results indicated that the patient had a heterozygous mutation in SOD1 exon 1,c.13G＞T(p.A5S),and his mother had a suspicious medical history but died without genetic verification.After discharge,the follow-up period lasted until August 21,2022,with a total of 38 months and a course of 62 months.Further review of the clinical characteristics of other patients with the same site mutation reported in the literature reveals that the progress of this patient with the mutation was slower than that of other patients with the same site mutation reported in the literature.Conclusion This study shows that gene sequencing is a powerful tool for diagnosing familial ALS.The mutation of c.13G＞T(p.A5S)in exon 1 of SOD1 is a rare pathogenic variation.The progress of patients with this subtype is slow,which further indicates that gene detection has important value in the diagnosis and prognosis of ALS.

Objective To explore esomeprazole(EMZ)on acetaminophen(APAP)pharmacokinetics and intestinal microbial balance.Methods A total of 14 rats were randomly allocated into two groups,with 7 rats in each group:acetaminophen group(APAP group),and acetaminophen+esomeprazole combination group(APAP+EMZ group),respectively.Rats in the combination group were fed in the metabolic cage.Equivalent 3.6 mg·kg-1·d-1 esomeprazole was administered intragastrically to the combination group for 14 days;Similarly,an equal volume of 0.9％sodium chloride soution(NaCl)was fed to the APAP group for 14 days.During this period,fecal samples were collected from the rats before and after 14 days of EMZ administration for microbial 16S rRNA sequencing.On the 15th day,both the APAP group and APAP+EMZ groups were administratered an equivalent of 44.82 mg·kg-1 APAP by the same method after the regular EMZ administration.The concentrations of APAP in rat plasma were determined by the UPLC-MS/MS method.Main pharmacokinetic parameters were processed and compared using the software DAS 3.0.1 and SPSS 24.0.Results The pharmacokinetic parameter Cmax of APAP was significantly different between APAP group and APAP+EMZ group(P＜0.05).Compared with APAP group,Cmax increased by 120.38％in the APAP+EMZ group.The pharmacokinetic parameters(AUC(0-∞)、CL、t 1/2、tmax)of APAP showed no statistical differences between APAP group and APAP+EMZ group(P＞0.05).The results of 16SrRNA of intestinal flora showed that the abundance of Lactobacillus,Bacteroides,Clostridium,and Escherichia decreased compared with that before drug administration,while the abundance of Bifidobacterium increased.However,the relative abundance of the above flora showed no prominent differences before and after the EMZ intervention(P＞0.05).Conclusions This study showed that when combining EMZ with APAP,the relative abundance of those related flora,which may influence the β-Glucuronidase,all changed to some extent,but made no difference in statistics.The effect of EMZ on the Cmax of APAP was statistically significant.However,the use of EMZ for two weeks did not alter the other pharmacokinetics of APAP by affecting the gut microbiota.

The purpose of this study was to investigate the damage mechanism of pathogenic E.coli on mouse brain microvascular endothelial cells(BMEC cells)and mouse alveolar macrophages(MH-S cells),as well as the lung and brain of healthy mice.In this study,BMEC cells and MH-S cells were infected with pathogenic E.coli strains,and cell morphological changes were observed.Plate counting method was used to detect the adhesion and invasion ability of the strains to cells and the number of bacteria in the lungs and brains of mice.RT-qPCR was used to detect the ex-pression of TNF-α,IL-1β and IL-6 genes in cells and mouse organs at different time periods.West-ern blot was used to detect the expression of p-NF-κB,p-JAK2 and p-STAT3 proteins related to inflammation in cells and mouse organs after infection.The results showed that the cell culture medium of the infection group was turbid,the cell vision became dark and blurred,some cells shrank and died,and more fragments were produced.The adhesion rate and invasion rate of BMEC cells at 3 h were significantly lower than those at 6 h(P＜0.050),and the adhesion rate and inva-sion rate of MH-S cells at 3 h were significantly higher than those at 6 h(P＜0.010).Infected mice had a large area of swelling and bleeding in the brain,and the lungs had different degrees of swell-ing and bleeding.The bacterial load in the brain and lung was the highest at 12 h.Compared with the control group,the mRNA expression levels of IL-1β,IL-6 and TNF-α in the infection group were significantly increased at 3 h and 6 h(P＜0.050),and the mRNA expression levels of inflam-matory factors in BMEC cells and MH-S cells were the highest at 6 and 3 h,respectively.The mR-NA expression of inflammatory factors in the brain and lung of infected mice showed a trend of in-creasing first and then decreasing with time,with the highest expression at 12 h after infection.The expression levels of p-NF-κB protein in BMEC cells,MH-S cells,lung and brain tissues of mice in the infection group were significantly higher than those in the control group(P＜0.001),and the expression levels of p-JAK2 protein and p-STAT3 protein were significantly lower than those in the control group(P＜0.050).The above results showed that pathogenic E.coli could adhere and invade BMEC cells and MH-S cells,colonize in lung and brain tissues of mice,promote the expres-sion of NF-κB protein in cells and tissues,inhibit the expression of JAK2 protein and STAT3 pro-tein,and then stimulate cells and tissues to produce inflammatory response.

Objective:To quantify the diagnostic index of probe-based confocal laser endomicroscopy (pCLE) for diagnosing Helicobacter pylori ( HP)-associated chronic atrophic gastritis (HpCAG), and to evaluate the efficacy of the quantified diagnostic index for HpCAG. Methods:The study was divided into two stages. The first stage prospectively included patients undergoing gastroscopy, endoscopic biopsy and 13C breath test from November 2021 to September 2022 at the Second Affiliated Hospital of Baotou Medical College. The capillary diameter (CD), cells spacing (CS), gland spacing (GS), and gland area (GA) in the pCLE field of offline video was measured with Image J. The diagnostic criteria of HpCAG by quantitative indicators under pCLE was established by analyzing the area under the receiver operating characteristic (ROC) curve (AUC). In the second stage, the cases with pCLE examination and 13C breath test at the Second Affiliated Hospital of Baotou Medical College from October 2021 to October 2022 were included. The cases that overlapped with the first stage were excluded. The trial was single-blind, with endoscopists and pathologists blind to each other's diagnoses. The diagnosis of pCLE was conducted according to the criteria obtained in the first stage, and the consistency between pCLE diagnosis and the results of histopathology and 13C breath test was analyzed. Results:The first stage enrolled 191 specimens from 35 patients. According to the pathological results of endoscopic biopsy and 13C breath test results, patients and gastric mucosa samples were divided into 4 groups, HP-positive CAG group ( n=59), HP-positive non-CAG group ( n=52), HP-negative CAG group ( n=40), and HP-negative non-CAG group ( n=40). ROC curve analysis results showed that in HP-positive patients, the optimal critical value of GS to distinguish between CAG and non-CAG gastric mucosa was 29.68 μm, and the AUC was the largest among the 4 parameters. In HP-negative patients, the optimal critical value of GS for distinguishing gastric mucosa from CAG and non-CAG was 23.57 μm, and the AUC was the largest among the 4 parameters. In patients with non-CAG, the optimal critical value for GS to distinguish HP-positive and HP-negative gastric mucosa was 20.57 μm, and the AUC was the largest among the 4 parameters. In patients with CAG, the optimal critical values of CD, CS, GS and GA to distinguish between HP-positive and HP-negative gastric mucosa were 13.23 μm, 1.38 μm, 34.03 μm and 6 066.5 μm 2, respectively, and the AUC were 0.608, 0.888, 0.849 and 0.900, respectively. Finally, GS was selected to distinguish between HpCAG and non-HpCAG gastric mucosa, and the optimal critical value was 31.71 μm. However, considering that it was difficult to measure the distance of 31.71 μm by the ruler below the image, the critical value was changed to 30 μm, so GS>30 μm was used as the diagnostic criteria for HpCAG in pCLE, and the diagnostic sensitivity and the specificity were 91.5% and 76.0%, respectively. In the second phase 224 specimens from 80 patients were observed. The sensitivity, the specificity, the positive predictive value, the negative predictive value and accuracy of pCLE (GS>30 μm) in the diagnosis of HpCAG were 96.5% (164/170), 88.9% (48/54), 96.5% (164/170), 88.9% (48/54) and 94.6% (212/224), respectively, with excellent diagnostic agreement with histopathology and 13C breath test (Kappa=0.854). Conclusion:The quantitative monitoring of gastric mucosal microstructure can be achieved under pCLE, and the quantifying indicators are helpful to improve the accuracy of HpCAG diagnosis.

The paper introduces professor ZHUANG Li-xing's clinical experience in treatment of dyskinesia of Parkinson's disease with acupuncture at triple-acupoint prescription. In pathogenesis, dyskinesia of Parkinson's disease refers to yang deficiency and disturbing wind. In treatment, acupuncture focuses on warming yang, promoting the circulation of the governor vessel, regulating the spirit and stopping trembling; and Baihui (GV 20), Suliao (GV 25) and Dingchanxue (Extra) are selected to be "trembling relief needling". In combination with Jin's three needling, named "three-trembling needling" "three-governor-vessel needling" and "three-spasm needling", the triple-acupoint prescription is composed. To ensure the favorable therapeutic effect, this prescription is modified according to the symptoms and the specific techniques of acupuncture are combined such as conducting qi, harmonizing yin and yang, and manipulating gently for reinforcing and reducing.
Humans ; Acupuncture Points ; Parkinson Disease/therapy* ; Acupuncture Therapy/methods* ; Acupuncture ; Dyskinesias

Terpenoids are important secondary metabolites of plants that possess both pharmacological activity and economic value. Terpene synthases(TPSs) are key enzymes in the synthesis process of terpenoids. In order to investigate the TPS gene family members and their potential functions in Schizonepeta tenuifolia, this study conducted a systematic analysis of the TPS gene family of S. tenuifolia based on the whole genome data of S. tenuifolia using bioinformatics methods. The results revealed 57 StTPS members identified from the genome database of S. tenuifolia. The StTPS family members encoded 285-819 amino acids, with protein molecular weights ranging from 32.75 to 94.11 kDa, all of which were hydrophilic proteins. The StTPS family members were mainly distributed in the cytoplasm and chloroplasts, exhibiting a random and uneven physical localization pattern. Phylogenetic analysis showed that the StTPS genes family were divided into six subgroups, mainly belonging to the TPS-a and TPS-b subfamilies. Promoter analysis predicted that the TPS gene family members could respond to various stressors such as light, abscisic acid, and methyl jasmonate(MeJA). Transcriptome data analysis revealed that most of the TPS genes were expressed in the roots of S. tenuifolia, and qRT-PCR analysis was conducted on genes with high expression in leaves and low expression in roots. Through the analysis of the TPS gene family of S. tenuifolia, this study identified StTPS5, StTPS18, StTPS32, and StTPS45 as potential genes involved in sesquiterpene synthesis of S. tenuifolia. StTPS45 was cloned for the construction of an prokaryotic expression vector, providing a reference for further investigation of the function and role of the TPS gene family in sesquiterpene synthesis.
Phylogeny ; Terpenes/metabolism* ; Plant Proteins/metabolism* ; Lamiaceae/genetics* ; Sesquiterpenes

Cytochrome P450 family 3 subfamily A(CYP3A),a major member of cytochrome P450(CYP)family,is one of the most important drug metabolizing enzymes in human.CYP3A includes 4 gene subtypes(CYP3A4,CYP3A5,CYP3A7,and CYP3A43),which is involved in 60%of drug metabolism in the human.It is not only widely distributed in normal tissues,but also significantly overexpressed in various tumor tissues.Recently,CYP3A has attracted great attention due to its involvement in the progression from chronic atrophic gastritis to gastric cancer,as well as the differential metabolism and resistance of chemotherapeutic drugs.Targeting CYP3A gene mediated-prodrug provides new ideas for the treatment of gastric cancer and is expected to become a new target for the diagnosis and treatment of gastric cancer.

OBJECTIVE: To analyze the association between outdoor artificial light-at-night (ALAN) exposure and overweight and obesity among children and adolescents aged 9 to 18 years in China. METHODS: Using follow-up data of 5 540 children and adolescents aged 9 to 18 years conducted from November 2019 to November 2020 in eight provinces of China, latitude and longitude were determined based on school addresses, and the mean monthly average nighttime irradiance at the location of 116 schools was extracted by the nearest neighbor method to obtain the mean outdoor ALAN exposure [unit: nW/(cm²·sr)] for each school. Four indicators of overweight and obesity outcomes were included: Baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence. Mixed effects Logistic regression was used to explore the association between ALAN exposure levels (divided into quintiles Q1-Q5) and baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence. In addition, a natural cubic spline function was used to explore the exposure response association between ALAN exposure (a continuous variable) and the outcomes. RESULTS: The prevalence of baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence among the children and adolescents in this study were 21.6%, 16.3%, 2.9% and 12.8%, respectively. The OR value for the association between ALAN exposure and baseline overweight and obesity was statistically significant when ALAN exposure levels reached Q4 or Q5, 1.90 (95%CI: 1.26-2.86) and 1.77 (95%CI: 1.11-2.83), respectively, compared with the children and adolescents in the Q1 group of ALAN exposure. Similar to the results for baseline overweight and obesity, the OR values for the association with persistent overweight and obesity were 1.89 (95%CI: 1.20-2.99) and 1.82 (95%CI: 1.08-3.06) when ALAN exposure levels reached Q4 or Q5, respectively, but none of the OR values for the association between ALAN and overweight and obesity progression and overweight and obesity incidence were statistically significant. Fitting a natural cubic spline function showed a non-linear trend between ALAN exposure and persistent overweight and obesity. CONCLUSION There is a positive association between ALAN exposure and overweight and obesity in children and adolescents, and the promotion of overweight obesity in children and adolescents by ALAN tends to have a cumulative effect rather than an immediate effect. In the future, while focusing on the common risk factors for overweight and obesity in children and adolescents, there is a need to improve the overweight and obesity-causing nighttime light exposure environment.
Humans ; Adolescent ; Child ; Overweight/etiology* ; Pediatric Obesity/etiology* ; Light Pollution ; Risk Factors ; China/epidemiology*