ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

Background Work-related musculoskeletal disorders (WMSDs) are one of the major occupational health problems faced by bus drivers and should receive special attention. Objective To explore the associations of weekly working hours and sleep quality with neck and lower back WMSDs among bus drivers, as well as assess the potential mediating role of sleep quality. Methods From June to December 2022, we recruited bus drivers from 5 subsidiaries of the Shenzhen Bus Group by convenient sampling method. Demographic characteristics, lifestyles, and work-related features of the bus drivers were collected through a questionnaire survey. The Pittsburgh Sleep Quality Index (PSQI) scale and the Musculoskeletal Disorders Survey Questionnaire were used to assess sleep quality and WMSDs respectively. Logistic regression models were applied to analyze the associations of weekly working hours and sleep quality with WMSDs in neck and lower back. Furthermore, mediation analysis was performed to investigate the role of sleep quality in the associations between weekly work hours and neck and lower back WMSDs. Results A total of 1792 valid questionnaires were collected, with a response rate of 95.07%. Among these, 89.3% of the bus drivers worked more than 40 h per week, and the positive rate of poor sleep quality was 28.2%. The overall positive rate of WMSDs within one year before the survey was 69.12%. Among different body regions, the leading positive rates were identified in neck and lower back regions, at 55.92% and 53.68%, respectively. The logistic regression model showed that compared to the bus drivers with weekly work hours ≤40 h, those weekly worked (40~48] h (OR=1.43, 95%CI: 1.02, 2.01; OR=1.65, 95%CI: 1.17, 2.34), (48~56] h (OR=2.69, 95%CI: 1.89, 3.83; OR=2.30, 95%CI: 1.62, 3.29) and ＞56 h (OR=2.63, 95%CI: 1.86, 3.74; OR=3.23, 95%CI: 2.27, 4.62) had significantly increased risk of WMSDs in neck and lower back. Additionally, when compared to those with good sleep quality, bus drivers with poor sleep quality had higher risks of both neck and lower back WMSDs (OR=4.08, 95%CI: 3.20, 5.23; OR=4.15, 95%CI: 3.26, 5.30, respectively). Further mediation analysis indicated that sleep quality partially mediated the associations between weekly working hours and both neck and lower back WMSDs, with 36.15% and 33.68% as the respective proportion of mediation. Conclusion The positive rate of WMSDs is high among bus drivers, and the most common WMSDs occur in neck and lower back. Long working hours and poor sleep quality are significantly associated with increased risks of neck and lower back WMSDs. Sleep quality may mediate the associations of weekly working hours with neck and lower back WMSDs.

OBJECTIVE To explore the construction of selection system for drug directory of the county-level medical community based on multi-criteria decision analysis， and provide decision-making basis for the selection of drug directory of medical community. METHODS Taking county-level medical community in Chongqing as an example，Delphi method and analytic hierarchy process were employed to construct the selection system for drug directory of the county-level medical community. Selected drugs were quantitatively scored based on the constructed index system， and the drug directory was selected according to the drug’s comprehensive score. The implementation effect of the directory was then evaluated through questionnaire surveys one year after the implementation of the directory. RESULTS The expert authority coefficients of the two rounds of consultation were＞ 0.8， with Kendall’s W values of 0.213 and 0.196， respectively （P＜0.001）. Finally， the selection system for drug directory of the medical community was determined to include five evaluation dimensions： safety， effectiveness， economy， accessibility， and innovation， along with eight evaluation indicators. In the drug directory selected according to the above method， the proportions of centrally procured drugs， medical insurance drugs， and essential drugs had all increased compared to before the selection； the comprehensive scores of chemical drugs ranged from 50.25 to 96.31 scores， and the proportion of drugs scoring between 70 and 100 scores had increased from 78.06% before selection to 85.82%. Among them， antiparasitic drugs had the highest comprehensive scores， while drugs for the digestive tract and metabolism were the most numerous. The evaluation scores of each indicator and the comprehensive scores of drugs in the drug directory after the selection process increased significantly than before selection （P＜ 0.05）. CONCLUSIONS The selection system for drug directory of the county-level medical community constructed in this study is scientific， objective and operable. This process facilitates the promotion of standardized and unified management of drugs in the medical community.

OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia （FD） in rats. METHODS In safety test， 40 rats were divided into blank control group， Shuangshu decoction low-dose， medium- dose and high-dose groups [108， 216， 324 g/（kg·d）， calculated by raw medicine， the same applies below]； they were given relevant medicine intragastrically， for continuous 14 days. The mortality and toxic reactions of rats were recorded， and the organ indexes of the liver， kidney， spleen， lung and heart of rats were calculated； the pathological morphological changes in the liver， kidney， spleen， lung， heart， stomach， duodenum， and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded， and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed， and blood routine and serum biochemical indicators were measured， in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group， model group， and Shuangshu decoction low-， medium-， and high-dose groups （9.45， 18.9， 37.8 g/kg）， with 10 rats in each group. Except for blank control group， rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide （3.5 mg/kg）. Rats in each group were administered the corresponding drug solution/normal saline intragastrically， once a day， for 14 consecutive days. After the last medication， fecal moisture content， intestinal propulsion rate， gastric emptying rate and serum level of motilin were all detected， and interstitial cell of Cajal （ICC） ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group， and no significant difference was found in organ coefficient， routine blood and serum biological index， compared to blank control group （P＞0.05）； no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that， compared with the blank control group， the fecal moisture content， gastric emptying rate， intestinal propulsion rate， and serum motilin levels in the model group were significantly decreased （P＜0.05）； in the colonic tissue， the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae， and the endoplasmic reticulum was dilated. Compared with model group， the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators （P＜ 0.05）； additionally， there was a large number of mitochondria in the ICC of the colonic tissue， with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats； its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion， as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.

OBJECTIVE To establish a method for determining the contents of clopidogrel （CLP）， clopidogrel carboxylate （CLP-C）， clopidogrel acyl-β-D-glucuronide （CLP-G） and contents of clopidogrel active metabolite （CAM） in rat plasma， and to investigate their in vivo pharmacokinetic characteristics. METHODS The Shisedo CAPCELL ADME column was used with a mobile phase consisting of water and acetonitrile （both containing 0.1% formic acid） in a gradient elution. The flow rate was 0.4 mL/min， and the column temperature was maintained at 20 ℃. The injection volume was 2 μL. The analysis was performed in positive ion mode using electrospray ionization with multiple reaction monitoring. The ion pairs for quantitative analysis were m/z 322.1→211.9 （for CLP）， m/z 308.1→197.9 （for CLP-C）， m/z 322.1→154.8 （for CLP-G）， m/z 504.1→154.9 [for racemic CAM derivative （CAMD）]. Six rats were administered a single intragastric dose of CLP （10 mg/kg）. Blood samples were collected before medication and at 0.08， 0.33， 0.66， 1， 2， 4， 6， 10， 23 and 35 hours after medication. The established method was used to detect the serum contents of various components in rats. Pharmacokinetic parameters were then calculated using WinNonlin 6.1 software. RESULTS The linear ranges for CLP， CLP-C and CAMD were 0.08-20.00， 205.00-8 000.00， and 0.04-25.00 ng/mL， respectively （r≥0.990）. The relative standard deviations for both intra-day and inter-day precision tests were all less than 15%， and the relative errors for accuracy ranged from －11.68% to 14.40%. The coefficients of variation for the matrix factors were all less than 15%， meeting the requirements for bioanalytical method validation. The results of the pharmacokinetic study revealed that， following a single intagastric administration of CLP in rats， the exposure to the parent CLP in plasma was extremely low. Both the area under the drug concentration-time curve （AUC0-35 h） and the peak concentration of the parent CLP were lower than those of its metabolites. The AUC0-35 h of the active metabolite CAM was approximately 43 times that of CLP， though it had a shorter half-life （2.53 h）. The inactive metabolite CLP-C exhibited the highest exposure level， but it reached its peak concentration the latest and was eliminated slowly. The AUC0-35 h of CLP-G was about four times that of CAM， and its half-life was similar to that of CLP-C. CONCLUSIONS This study successfully established an liquid chromatography-tandem mass spectrometry method for the determination of CLP and its three metabolites， and revealed their pharmacokinetic characteristics in rats. Specifically， the parent drug CLP was rapidly eliminated， while the inactive metabolites CLP-C and CLP-G exhibited long half-lives， and active metabolite CAM displayed a transient exposure pattern.

ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis （AIH）-related decompensated cirrhosis， to identify independent predictive factors， and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 （n=211）. The primary endpoint was achievement of recompensation， and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up， the patients were divided into the recompensation group （n=16） and the persistent decompensation group（n=150）.The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the Kaplan-Meier method was used for survival analysis； the Cox proportional-hazards regression model was used to identify independent predictive factors， and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled， with a median age of 55.0 years and a median follow-up time of 44.0 months， and female patients accounted for 87.2%. Among the 211 patients， 61 （with a cumulative proportion of 35.5%） achieved recompensation. Compared with the persistent decompensation group， the recompensation group had significantly higher white blood cell count， platelet count （PLT）， total bilirubin （TBil）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bile acid， prothrombin time， international normalized ratio （INR）， SMA positive rate， Model for End-Stage Liver Disease （MELD） score， Child-Pugh score， and rate of use of glucocorticoids （all P0.05）， as well as significantly lower age at baseline， number of complications， and death/liver transplantation rate （all P0.05）. At 3 and 12 months after treatment， the recompensation group had continuous improvements in AST， TBil， INR， IgG， MELD score， and Child-Pugh score， which were significantly lower than the values in the persistent decompensation group （all P0.05）， alongside with continuous increases in PLT and albumin， which were significantly higher than the values in the persistent decompensation group （P0.05）. The multivariate Cox regression analysis showed that baseline ALT （hazard ratio ［HR］=1.067， 95% confidence interval ［CI］： 1.010 — 1.127， P=0.021）， IgG （HR=0.463，95%CI：0.258 — 0.833， P=0.010）， SMA positivity （HR=3.122，95%CI：1.768 — 5.515， P0.001）， and glucocorticoid therapy （HR=20.651，95%CI：8.744 — 48.770， P0.001） were independent predictive factors for recompensation， and the nomogram model based on these predictive factors showed excellent predictive performance （C-index=0.87，95%CI：0.84 — 0.90）. ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity， a high level of ALT， a low level of IgG， and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.

BACKGROUND: Huaier granule is an important medicinal fungus extract widely used in cancer treatment. Previous retrospective studies have reported its effectiveness in breast cancer patients, but the imbalanced baseline characteristics of participants could have biased the results. Therefore, this retrospective study aimed to examine the efficacy of Huaier granule on the prognosis of breast cancer patients. METHODS: In this single-center cohort study, breast cancer patients diagnosed and treated at the Guangdong Provincial Hospital of Chinese Medicine between 2009 and 2017 were selected. The data were retrospectively analyzed and divided into two groups according to whether the patients received Huaier granules. The propensity score matching (PSM) method was used to eliminate selection bias. The disease-free survival (DFS) and overall survival (OS) for these groups were compared using the Kaplan-Meier method and the Cox regression. RESULTS: This study included 214 early invasive breast cancer patients, 107 in the Huaier group and 107 in the control group. In the Kaplan-Meier analysis, the 2-year and 5-year DFS rates were significantly different in the Huaier group and control group (hazard ratio [HR], 0.495; 95% confidence interval [CI], 0.257-0.953; P = 0.023). The 2-year and 5-year OS rates were also significantly different (HR, 0.308; 95% CI, 0.148-0.644; P = 0.001). On multivariable Cox regression, Huaier granule was associated with improved DFS (HR, 0.440; 95% CI, 0.223-0.868; P = 0.018) and OS (HR, 0.236; 95% CI, 0.103-0.540; P = 0.001). CONCLUSION In this retrospective study, Huaier granules improved the DFS and OS of early invasive breast cancer patients, providing real-world evidence for further prospective studies on treating breast cancer with Huaier granules.
Humans ; Breast Neoplasms/mortality* ; Retrospective Studies ; Female ; Propensity Score ; Middle Aged ; Adult ; Prognosis ; Disease-Free Survival ; Kaplan-Meier Estimate ; Aged ; Proportional Hazards Models ; Complex Mixtures/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Trametes

This study investigates the material basis and mechanism of Arisaematis Rhizoma Preparatum in the treatment of chronic obstructive pulmonary disease(COPD) using animal experiments, component analysis, network pharmacology, and molecular docking. A mouse model of COPD was constructed by cigarette smoke and lipopolysaccharide(LPS). Blood gas analysis was performed to measure the pH and partial pressure of carbon dioxide(PCO_2) in the blood of the mice. Lung tissue sections were analyzed using HE staining, and the effects of Arisaematis Rhizoma Preparatum water extract on inflammatory factors(TNF-α, IL-6, and IL-1β) and the PI3K/AKT signaling pathway in the lung tissue of COPD model mice were studied by qPCR and Western blot. The composition of the Arisaematis Rhizoma Preparatum water extract was analyzed using UPLC Q-Exactive Orbitrap MS. The SwissTargetPrediction database was used to predict the targets of the chemical components in Arisaematis Rhizoma Preparatum. GeneCards, OMIM, TTD, PharmGKB and DrugBank disease databases were used to screen for COPD targets, and the potential targets of Arisaematis Rhizoma Preparatum in treating COPD were identified. A protein-protein interaction(PPI) network of intersection targets was constructed and analyzed using the STRING database and Cytoscape 3.9.0, and core genes were screened. GO functional analysis and KEGG pathway enrichment analysis were performed using R language, and molecular docking verification was conducted using AutoDock Vina software. The results of the animal experiments showed that Arisaematis Rhizoma Preparatum water extract improved pulmonary ventilation function in COPD model mice, reduced lung inflammatory cells, decreased alveolar cavities, and improved lung tissue condition. The levels of inflammatory factors TNF-α, IL-6 and IL-1β were decreased, and the phosphorylation levels of PI3K and AKT were inhibited. Fifty-two chemical components were identified from Arisaematis Rhizoma Preparatum, and 440 intersection targets related to COPD were found. Nine key components were screened, including hydroxyphenylethylamine, L-tyrosine, L-tyrosyl-L-alanine, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid, methyl azelate, zingerone, 6-gingerol, linoleamide, and linoleoyl ethanolamine. Five core targets were identified, including AKT1, TNF, STAT3, ESR1, and IL1B. The PI3K/AKT pathway was identified as the key pathway for the treatment of COPD with Arisaematis Rhizoma Preparatum. Molecular docking results showed that 75% of the binding energies of key components and core targets were less than-5 kcal·mol~(-1), indicating good binding affinity. In conclusion, Arisaematis Rhizoma Preparatum may improve pulmonary ventilation function, enhance lung pathological morphology, and reduce pulmonary inflammation in COPD model mice by inhibiting the PI3K/AKT signaling pathway and downregulating TNF-α, IL-6, and IL-1β inflammatory factors. The material basis may be associated with L-tyrosyl-L-alanine, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid, zingerone and 6-gingerol, and AKT1 and TNF may be the primary targets.
Animals ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rhizome/chemistry* ; Humans ; Molecular Docking Simulation ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Signal Transduction/drug effects* ; Lung/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Interleukin-6/immunology*

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size