ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

Objective To understand the application effect of early screening scale and behavioral intervention effect in children with autism spectrum disorder (ASD). Methods A total of 348 children with suspected ASD were selected and evaluated using the Modified Checklist for Autism in Toddlers (M-CHAT) and Autism Behavior Checklist (ABC). The evaluation results were compared with those from the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Children enrolled were given Early start Denver model (ESDM) intervention. The evaluation results of Gesell Developmental Scale and Autism Treatment Evaluation Checklist (ATEC) scores were compared before and after intervention. Results The sensitivity, specificity, accuracy and Kappa value of M-CHAT for evaluating ASD in children aged 1-3 years were 89.53%, 90.70%, 89.92% and 0.78. The corresponding values of ABC were 78.49%, 81.40%, 79.46% and 0.56. The sensitivity, specificity, accuracy and Kappa value of M-CHAT for evaluating children aged >3-6 years were 87.30%, 77.78%, 84.44% and 0.64. The corresponding values of ABC were 85.71%, 77.78%, 83.33% and 0.62. The sensitivity and accuracy of M-CHAT were higher than ABC for evaluating ASD in children aged 1-3 years (P<0.05). There were no significant differences in sensitivity, specificity and accuracy between M-CHAT and ABC for evaluating ASD in children aged 3-6 years (P>0.05). After intervention, development quotients (DQ) of personal-social aspects, adaptability, language, gross motor, and fine motor of children with ASD were higher than those before intervention (P<0.05). ATEC scores for language, behavior, sensation, and social contact of children with ASD were lower than those before intervention (P<0.05). Conclusion M-CHAT and ABC both can be used for early screening of ASD in children, especially M-CHAT. Early behavioral intervention can effectively improve the condition and developmental level of children with ASD.

ObjectiveTo analyze the epidemiological characteristics of long COVID and to investigate its main influencing factors by examining individuals infected with SARS-CoV-2 between March and June 2022 in two communities in Shanghai, to lay the foundation for further research on the mechanism and clinical treatment of long COVID, and to provide the basis for the development of inexpensive, convenient, and feasible prevention and intervention strategies. MethodsA cross-sectional study was conducted, enrolling 6 410 individuals infected with SARS-CoV-2. Data were collected through a questionnaire survey. The incidence and common symptoms of long COVID were analyzed, along with their associations with demographic characteristics, medical history, and behavioral factors. A logistic regression model was used to identify the major factors associated with the development of long COVID symptoms. ResultsThe overall incidence rate of long COVID among the study population was 13.9%. The most commonly reported symptoms included fatigue (65.1%), attention disorders (23.1%), and cough (16.9%). The analysis showed that having underlying chronic diseases (OR=2.580, 95%CI: 2.165‒3.074), a history of allergies (OR=1.418, 95%CI: 1.003‒1.971), current smoking (OR=1.461, 95%CI: 1.013‒2.079), ever smoking (OR=2.462, 95%CI: 1.687‒3.551), a greater number of symptoms during the acute phase [1 symptom (OR=1.778, 95%CI: 1.459‒2.162), 2 symptoms (OR=2.749, 95%CI: 2.209‒3.409), ≥3 symptoms (OR=7.792, 95%CI: 6.333‒9.593)] and aggravated symptoms during the acute phase (OR=1.082, 95%CI: 1.070‒1.094) were factors associated with a higher risk of developing long COVID symptoms. Additionally, individuals who had consumed alcohol in the past year (OR=1.914, 95%CI: 1.344‒2.684) were more prone to objective long COVID symptoms. Among individuals under 50 years of age, females (OR=1.427, 95%CI: 1.052‒1.943) were more likely to develop objective long COVID symptoms. ConclusionThis study has identified the diversity of long COVID symptoms, which involve multiple organs and systems, including fatigue, attention disorders, cough, and joint pain. It has also revealed associations between long COVID and various demographic factors (e.g., age, gender), personal medical history (e.g., underlying chronic diseases, history of allergies), acute-phase characteristics (e.g., number and severity of symptoms), and behavioral factors (e.g., smoking, alcohol consumption). These findings highlight the need for further research and ongoing surveillance of long COVID and may inform the development of more targeted health management strategies for specific populations.

The quality of traditional Chinese medicine (TCM) prescriptions (TCMPs) is critical to clinical efficacy; however, evaluating their consistency and identifying sources of variability remain challenging. This study proposes an integrated strategy to assess the quality of 100 widely sold TCMPs. A "one-for-all" chromatographic method was employed to analyze 645 sample batches. This large-scale data collection enabled statistical evaluations, such as hierarchical cluster analysis (HCA) and similarity heatmap, to identify quality inconsistencies. The introduction of a TCM-specific mass spectrometry (MS) database allowed for rapid, automated annotation of chemicals across 100 prescriptions and facilitated the tracing of raw material sources. Results indicate that 19% of prescriptions exhibited chemical inconsistencies, which are associated with high market value, low pricing, and substantial price disparities. The MS database allowed rapid annotation of 761 and 673 compounds in positive and negative modes, respectively, in 100 TCMPs, with 73 prescriptions reported for the first time. The tracing efforts succeeded in identifying >40% of the raw material sources for 51 prescriptions. P93 (Yinianjin (YNJ)) is a case in which the chromatographic profiles from three manufacturers displayed inconsistencies. Analysis using the database traced divergent peaks to Rhei Radix et R hizoma (RRER). Verification with self-prepared samples confirmed that manufacturers utilized three distinct botanical sources. This integrated strategy provides a scalable framework for quality control in TCMPs.

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Objective To explore the general surgery patients with postoperative incision infection(SSI)of pathogenic microorganism distribution characteristics and serum lactate dehydrogenase(LDH),interleukin(IL)-6 to the predictive value of infection.Methods A total of 100 patients who underwent surgery in the General Surgery Department of the hospital from January 2021 to June 2023 were selected as the research ob-jects.According to the occurrence of postoperative infection,the patients were divided into infection group(28 cases)and non-infection group(72 cases).The basic data of the patients were collected,including age,gender,operation type,operation time,incision type,and incision healing.Bacterial culture and pathogen identification were performed on the incision secretion of patients under sterile conditions.At the same time,the serum LDH and IL-6 levels of the patients on the first and third day after operation were detected,and the differences of LDH and IL-6 levels between the infection group and the non-infection group were compared.Pearson cor-relation analysis was used to analyze the correlation between serum LDH level and IL-6.Multivariate Logistic regression analysis was used to analyze the influencing factors of SSI.The receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic efficacy of serum LDH and IL-6 levels for SSI.Results A-mong the 100 patients,28 patients developed SSI,and the infection rate was 28％.There were significant differences in age,operation time,and incision type between the infection group and the non-infection group(P＜0.05).The results of bacterial culture showed that a total of 35 strains of bacteria were isolated from the patients in the infection group,of which Gram-positive bacteria accounted for 54.29％and Gram-negative bac-teria accounted for 45.71％,mainly Staphylococcus aureus(14 strains),Pseudomonas aeruginosa(7 strains),and Escherichia coli(5 strains).The serum levels of LDH and IL-6 in the infection group were higher than those in the non-infection group on postoperative days 1 and 3(P＜0.05).The serum level of LDH in the in-fection group was positively correlated with IL-6(r=0.512,P＜0.001).Multivariate Logistic regression a-nalysis showed that age,operation time,type of incision,and serum LDH and IL-6 levels on postoperative day 3 were independent risk factors for SSI(P＜0.05).ROC curve analysis showed that serum LDH and IL-6 lev-els had a high diagnostic efficacy for SSI,with an area under the curve of 0.89 and 0.88,the best cut-off values of 210 U/L and 15 pg/mL,the sensitivity of 82.14％and 85.71％,and the specificity of 78.57％and 80.36％,respectively.Conclusion Staphylococcus aureus and Pseudomonas aeruginosa are the main pathogenic micro-organisms of SSI in general surgical patients.Serum LDH and IL-6 levels can be used as predictors of SSI,which is of great significance for early diagnosis and treatment of infection.

Objective:To analyze the survival of pneumoconiosis patients in Guangzhou from 1958 to 2018, explore the factors affecting the survival of pneumoconiosis, and provide scientific basis for formulating the guidelines and policies for treatment and assistance of pneumoconiosis.Methods:From July 2019 to January 2020, 1194 cases of occupational pneumoconiosis patients diagnosed by institutions qualified for pneumoconiosis diagnosis in Guangzhou from June 1, 1958 to December 31, 2018 were studied. Excluding 258 patients who lacked survival data, 936 patients were included in the pneumoconiosis survival analysis. Life table method was used to estimate the survival rate, Kaplan-Meier method was used to draw the survival curve, log-rank test was used to compare the groups, and Cox proportional risk regression model was used to analyze the influencing factors of survival.Results:The 10, 20 and 30 years cumulative survival rates of pneumoconiosis patients in Guangzhou were 62.8%, 35.2% and 15.4%, respectively. The median survival time was 19.4 years. log-rank test showed that there were statistically significant differences in the survival curves of pneumoconiosis patients between group without tuberculosis and group with tuberculosis ( P<0.001), and there were statistically significant differences among different stages and categories of pneumoconiosis ( P<0.001). Age of exposure to dust ( HR=1.03, 95% CI: 1.01-1.05), age of diagnosis ( HR=1.02, 95% CI: 1.00-1.04), combined pulmonary tuberculosis ( HR=1.46, 95% CI: 1.18-1.81), stage of pneumoconiosis (stage Ⅲ vs. stage Ⅰ, HR=2.26, 95% CI: 1.47-3.48) and categories of pneumoconiosis (fibrogenic mineral dust pneumoconiosis and metallogenic pneumoconiosis, HR=2.45, 95% CI: 1.61-3.74; non-fibrogenic mineral pneumoconiosis and metallogenic pneumoconiosis, HR=2.67, 95% CI: 1.47-4.87; mixed pneumoconiosis and metallogenic pneumoconiosis, HR=2.25, 95% CI: 1.11-4.56) were the factors affecting the survival time of pneumoconiosis patients ( P<0.05) . Conclusion:Pulmonary tuberculosis may increase the risk of death in patients with pneumoconiosis. Mineral dust pneumoconiosis, mixed pneumoconiosis and stage Ⅲ pneumoconiosis may also have higher risk of death.

Objective:To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency.Methods:This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively.Results:The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 μmol/L) was found in all patients, and decreased to 20-70 μmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders.Conclusions:Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.

Objective:To analyze the survival of pneumoconiosis patients in Guangzhou from 1958 to 2018, explore the factors affecting the survival of pneumoconiosis, and provide scientific basis for formulating the guidelines and policies for treatment and assistance of pneumoconiosis.Methods:From July 2019 to January 2020, 1194 cases of occupational pneumoconiosis patients diagnosed by institutions qualified for pneumoconiosis diagnosis in Guangzhou from June 1, 1958 to December 31, 2018 were studied. Excluding 258 patients who lacked survival data, 936 patients were included in the pneumoconiosis survival analysis. Life table method was used to estimate the survival rate, Kaplan-Meier method was used to draw the survival curve, log-rank test was used to compare the groups, and Cox proportional risk regression model was used to analyze the influencing factors of survival.Results:The 10, 20 and 30 years cumulative survival rates of pneumoconiosis patients in Guangzhou were 62.8%, 35.2% and 15.4%, respectively. The median survival time was 19.4 years. log-rank test showed that there were statistically significant differences in the survival curves of pneumoconiosis patients between group without tuberculosis and group with tuberculosis ( P<0.001), and there were statistically significant differences among different stages and categories of pneumoconiosis ( P<0.001). Age of exposure to dust ( HR=1.03, 95% CI: 1.01-1.05), age of diagnosis ( HR=1.02, 95% CI: 1.00-1.04), combined pulmonary tuberculosis ( HR=1.46, 95% CI: 1.18-1.81), stage of pneumoconiosis (stage Ⅲ vs. stage Ⅰ, HR=2.26, 95% CI: 1.47-3.48) and categories of pneumoconiosis (fibrogenic mineral dust pneumoconiosis and metallogenic pneumoconiosis, HR=2.45, 95% CI: 1.61-3.74; non-fibrogenic mineral pneumoconiosis and metallogenic pneumoconiosis, HR=2.67, 95% CI: 1.47-4.87; mixed pneumoconiosis and metallogenic pneumoconiosis, HR=2.25, 95% CI: 1.11-4.56) were the factors affecting the survival time of pneumoconiosis patients ( P<0.05) . Conclusion:Pulmonary tuberculosis may increase the risk of death in patients with pneumoconiosis. Mineral dust pneumoconiosis, mixed pneumoconiosis and stage Ⅲ pneumoconiosis may also have higher risk of death.