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.

Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals ; Rats, Sprague-Dawley ; Rats ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Oxytocin/genetics* ; Receptors, Oxytocin/genetics* ; Humans ; Osteoporosis, Postmenopausal/genetics* ; Bone and Bones/drug effects* ; Brain/drug effects* ; Bone Marrow/drug effects*

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

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.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

The value of combined detection of neutrophil apolipoprotein (HNL), serum amyloid A (SAA), procalcitonin (PCT) and C-reactive protein (CRP) in the differential diagnosis of bacterial and viral infectious diseases. A retrospective study was conducted to collect the clinical data of infected patients and healthy people in the clinical department of Shaanxi Provincial People's Hospital from September to December in 2022. 100 patients with confirmed infection were divided into bacterial infection group (n=50) and virus infection group (n=50), and 50 healthy people were selected as control group (n=50). Fasting venous blood was collected at the initial stage of admission or on the day of physical examination. HNL was detected by double antibody sandwich method, SAA and CRP were detected by nephelometry, and PCT was detected by chemiluminescence method. The efficacy of infection markers in the differential diagnosis of bacterial infection and viral infection in infected patients was evaluated. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of HNL, SAA, PCT and CRP in bacterial and viral infectious diseases; Logistic regression was used to analyze the influence of each index on the diagnostic efficiency. The results showed that the levels of HNL (126.60±33.32) ng/ml, PCT (28.02±11.37) ng/ml and CRP (36.13±14.37) mg/L in bacterial infection group were significantly higher than those of HNL (47.72±15.94) ng/ml, PCT (1.27±0.40) ng/ml, CRP (18.77±10.66) mg/L in virus group and HNL (38.21±12.53) ng/ml, PCT (0.38±0.12) ng/ml and CRP (4.13±1.07) mg/L in control group. The level of HNL increased most significantly (F=89.228, P<0.05). The area under ROC curve (AUC) from large to small was HNL+SAA+PCT+CRP (0.976), HNL (0.907), PCT (0.885), CRP (0.856), SAA (0.790), SAA/CRP (0.733). The level of SAA/CRP in virus infection group (94.05±3.75) was significantly higher than that in bacteria group (17.70±3.69) and control group (3.89±1.50) (F=84.005, P<0.05). The area under ROC curve (AUC) from large to small was HNL+SAA+PCT+CRP (0.986), SAA/CRP (0.956), SAA (0.878), HNL (0.768), CRP (0.742), PCT (0.730). In conclusion, HNL has the best auxiliary diagnostic efficacy in bacterial infection, followed by PCT; SAA/CRP has the best auxiliary diagnostic efficacy in viral infection, followed by SAA; the combined detection of serum HNL, SAA, PCT and CRP may be helpful for the differential diagnosis of bacterial and viral infections.
Humans ; C-Reactive Protein ; Procalcitonin ; Serum Amyloid A Protein ; Retrospective Studies ; Virus Diseases/diagnosis* ; Bacteria ; Communicable Diseases ; Bacterial Infections/diagnosis*