ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang （QLHQT） on nonalcoholic steatohepatitis （NASH）. MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling， mice were randomly assigned to the model group， low-， medium-， and high-dose QLHQT groups （0.51， 1.02， and 2.04 g·kg^-1）， and a positive control metformin group， with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C）， as well as hepatic TC， TG， and LDL-C contents， were determined by biochemical assays. Hematoxylin-eosin （HE） staining and oil red O staining were used to evaluate liver histopathology and lipid deposition， respectively. Flow cytometry， enzyme-linked immunosorbent assay （ELISA）， and Real-time polymerase chain reaction （Real-time PCR） were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group， body weight and serum and hepatic levels of TC， TG， and LDL-C were significantly increased in the model group （P<0.01）. Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm， accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased， whereas the proportion of CD206-positive cells was markedly decreased （P<0.05）. Hepatic inducible nitric oxide synthase （iNOS） levels and tumor necrosis factor-α （TNF-α） mRNA expression were significantly increased， while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased （P<0.01）. The protein expression levels of Toll-like receptor 4 （TLR4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） in the liver were significantly increased （P<0.01）. Compared with the model group， body weight was reduced in the high-， medium-， and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC， TG， and LDL-C levels were significantly decreased （P<0.01）. Liver histopathology showed alleviated hepatic lipid deposition， with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased， whereas the proportions of CD206-positive cells were significantly increased in the high-， medium-， and low-dose QLHQT groups （P<0.05）. Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased （P<0.01）， whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased （P<0.01）. The hepatic protein expression levels of TLR4， TRAF6， and MyD88 were significantly decreased， while signal transducer and activator of transcription 6 （STAT6） phosphorylation was significantly increased （P<0.05， P<0.01）. There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice， and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.

ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang （QLHQT） on nonalcoholic steatohepatitis （NASH）. MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling， mice were randomly assigned to the model group， low-， medium-， and high-dose QLHQT groups （0.51， 1.02， and 2.04 g·kg^-1）， and a positive control metformin group， with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol （TC）， triglycerides （TG）， and low-density lipoprotein cholesterol （LDL-C）， as well as hepatic TC， TG， and LDL-C contents， were determined by biochemical assays. Hematoxylin-eosin （HE） staining and oil red O staining were used to evaluate liver histopathology and lipid deposition， respectively. Flow cytometry， enzyme-linked immunosorbent assay （ELISA）， and Real-time polymerase chain reaction （Real-time PCR） were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group， body weight and serum and hepatic levels of TC， TG， and LDL-C were significantly increased in the model group （P<0.01）. Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm， accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased， whereas the proportion of CD206-positive cells was markedly decreased （P<0.05）. Hepatic inducible nitric oxide synthase （iNOS） levels and tumor necrosis factor-α （TNF-α） mRNA expression were significantly increased， while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased （P<0.01）. The protein expression levels of Toll-like receptor 4 （TLR4）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） in the liver were significantly increased （P<0.01）. Compared with the model group， body weight was reduced in the high-， medium-， and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC， TG， and LDL-C levels were significantly decreased （P<0.01）. Liver histopathology showed alleviated hepatic lipid deposition， with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased， whereas the proportions of CD206-positive cells were significantly increased in the high-， medium-， and low-dose QLHQT groups （P<0.05）. Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased （P<0.01）， whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased （P<0.01）. The hepatic protein expression levels of TLR4， TRAF6， and MyD88 were significantly decreased， while signal transducer and activator of transcription 6 （STAT6） phosphorylation was significantly increased （P<0.05， P<0.01）. There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice， and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.

Cerebral venous sinus thrombosis （CVST） is a rare cerebrovascular disease characterized by the formation of blood clots in the intracranial venous system due to various causes， resulting in obstruction of intracranial blood flow or cerebrospinal fluid circulation disorder. This disease often has diverse clinical symptoms， including increased intracranial pressure and focal neurological deficits. Antithrombin Ⅲ （AT Ⅲ）， encoded by the SERPINC1 gene， acts as a serine protease inhibitor for thrombin and coagulation factors Ⅻα， Ⅺα， Ⅸα， and Ⅹα， and antithrombin deficiency caused by SERPINC1 gene mutations is a risk factor for thrombosis. This article reports a case of CVST due to ATⅢ deficiency caused by common mutations in both the intron and exon regions of the SERPINC1 gene in our hospital.

OBJECTIVE: To observe the effect of acupuncture at "four pharyngeal points" on simple vocal tics with liver hyperactivity disturbed wind in children. METHODS: Sixty children with simple vocal tics of liver hyperactivity disturbed wind were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases). The control group was given Changma Xifeng tablets orally, 3 times a day, while the observation group was treated with acupuncture at "four pharyngeal points" on the basis of the treatment in the control group, 15-20 min a time, once daily for 7 days, with a 3-day break. Both groups were treated for 3 months. The TCM syndrome score and Yale global tic severity scale (YGTSS) score of the two groups were observed before treatment and after 1, 2, 3 months of treatment, the disappearance time of simple vocal tics was recorded, and the therapeutic efficacy was evaluated after treatment. RESULTS: After 1, 2, 3 months of treatment, the TCM syndrome scores and YGTSS scores of the two groups were decreased compared with those before treatment (P<0.01, P<0.05), and the scores of the observation group were lower than those in the control group (P<0.05, P<0.01). The disappearance time of simple vocal tics in the observation group was earlier than that in the control group (P<0.05). The effective rate of the observation group was 93.1% (27/29), which was higher than 73.3% (22/30) in the control group (P<0.05). CONCLUSION Acupuncture at "four pharyngeal points" could improve symptoms in children with simple vocal tics of liver hyperactivity disturbed wind, and shorten the disappearance time of simple vocal tics.
Humans ; Male ; Acupuncture Points ; Female ; Child ; Acupuncture Therapy ; Drugs, Chinese Herbal/administration & dosage* ; Child, Preschool ; Liver/drug effects* ; Tics/drug therapy* ; Treatment Outcome

Objective To assess the clinical value of conventional contrast enhanced CT(CECT),multi parameter energy spectrum CT,and contrast enhanced MR(CEMR)imaging methods in evaluating hepatocellular carcinoma(HCC)after TACE treatment.Methods The clinical data of 66 HCC patients,who underwent TACE treatment at authors' hospital and received CECT,multi parameter energy spectrum CT and CEMR in 1-3 months after treatment,were retrospectively analyzed.Taking DSA results as the gold standard,the recurrent or residual lesions detected by DSA were classified as positive lesions,while the lesions having no obvious recurrence or residues were classified as negative lesions.The positive lesions that were detected by both DSA and other imaging methods were regarded as true positive lesions.The accuracy,sensitivity,specificity,Kappa value were used to compare the values of CECT,multi parameter energy spectrum CT and CEMR in evaluating the positive/negative lesions of HCC after TACE treatment,and the number of detected lesions and accuracy rate were used to evaluate the values of the above imaging methods in demonstrating the iodine oil deposition status and in diagnosing true positive lesions.Results A total of 133 positive lesions and 35 negative lesions were detected by DSA.The accuracy of CEMR in diagnosing lesions was highest,the accuracy rate was 88.70％(both P＜0.05);CEMR and energy spectrum CT had the highest diagnostic efficiency,the sensitivity for positive lesions was 92.31％and 81.95％respectively,and the difference between the two methods was not statistically significant(P＞0.05).No statistically significant difference in the ability of diagnosing negative lesions existed between each other among the three groups(all P＞0.05).The Kappa value suggested that the ability for diagnosing lesions after TACE treatment of CEMR was stronger than that of energy spectrum CT(Kappa value was 0.68 and 0.56 respectively,both P＜0.05).CECT and multi parameter energy spectrum CT had the same accuracy in evaluating the iodine oil deposition status(both were 91.7％).No statistically significant difference in diagnosing even iodine oil deposition of the true positive lesions existed between each other among the three groups(all P＞0.05).For diagnosing uneven iodine oil deposition of the true positive lesions,CEMR had the highest accuracy(92.50％,all P＜0.05).Conclusion CEMR and multi parameter energy spectrum CT have more reliable diagnostic performance than conventional CECT,besides,CEMR has the highest diagnostic performance.However,multi parameter energy spectrum CT and CECT are the better choice for evaluating the deposition status of iodine oil.

Objective To study the chemical composition of and identify its active components.Methods The chemical constituents of Dendrobium Primulinum were extracted using solvents,followed by separation through silica gel and gel column chromatography,with structural identification performed via spectral analysis.The in vitro activity screening of some compounds was conducted using the MTT assay.Results Seven compounds were isolated and identified from Dendrobium primulinum,namely 7-dihydroxy-2,4-methoxyphenanthrene(1),densiflorol B(2),3,4,7-trihydroxy-2-methoxy-9,10-dihydrophenanthrene(3),thunalbene(4),phillygenin(5),3 β-hydroxy-5 α,8 α-epidioxyergosta-6,22-diene(6)、4-hydroxy-3,5-dimethoxy--cinnamaldehyde(7).Antitumor activity tests were performed on compounds 1 to 5,revealing that compound 1 exhibited strong inhibitory activity against the MCF-7/S cell line,with an IC50 of 5.13 μM.Conclusion Compounds 1 to 6 are reported for the first time from Dendrobium primulinum,while compound 7 is reported for the first time from this genus.

Fungal keratitis is a serious blinding eye disease. The development of fungal infections depends primarily on the interaction of fungal virulence with host immune defense factors. The cornea is considered an immune-privileged organ, and resident macrophages are the main immune cells that respond to the heterogeneity exhibited by the microenvironment with their polarization. In the early stage of infection, macrophages polarize towards M1, which promotes inflammation and facilitates fungal clearance but produces a cellular storm that exacerbates immune damage; in the late stage of infection, macrophages polarize towards M2, which suppresses the inflammatory response and facilitates tissue repair, but may be immunosuppressed or even immune escape to the detriment of pathogen clearance. The balance between pro-inflammatory and anti-inflammatory responses is key to maintaining the functional integrity of the cornea. Current antifungal drug therapy is limited, so it is particularly important to find a therapeutic target for the inflammatory response triggered by the immune response in addition to antifungal therapy. In this review, the functional and phenotypic characterization of macrophage subsets associated with fungal keratitis was reviewed, more in-depth research is needed to explore the specific mechanisms by which macrophage polarization and their impact on fungal keratitis. Targeted regulation of macrophage differentiation based on their phenotype and function could be an effective approach to treat and manage fungal keratitis in the future.

Background::Clinical opportunistic screening is a cost-effective cancer screening modality. This study aimed to establish an easy-to-use diagnostic model serving as a risk stratification tool for identification of individuals with malignant gastric lesions for opportunistic screening.Methods::We developed a questionnaire-based diagnostic model using a joint dataset including two clinical cohorts from northern and southern China. The cohorts consisted of 17,360 outpatients who had undergone upper gastrointestinal endoscopic examination in endoscopic clinics. The final model was derived based on unconditional logistic regression, and predictors were selected according to the Akaike information criterion. External validation was carried out with 32,614 participants from a community-based randomized controlled trial.Results::This questionnaire-based diagnostic model for malignant gastric lesions had eight predictors, including advanced age, male gender, family history of gastric cancer, low body mass index, unexplained weight loss, consumption of leftover food, consumption of preserved food, and epigastric pain. This model showed high discriminative power in the development set with an area under the receiver operating characteristic curve (AUC) of 0.791 (95% confidence interval [CI]: 0.750–0.831). External validation of the model in the general population generated an AUC of 0.696 (95% CI: 0.570–0.822). This model showed an ideal ability for enriching prevalent malignant gastric lesions when applied to various scenarios.Conclusion::This easy-to-use questionnaire-based model for diagnosis of prevalent malignant gastric lesions may serve as an effective prescreening tool in clinical opportunistic screening for gastric cancer.

Objective:To preliminarily investigate the effect of blue light on the biological activity of human skin keratinocytes, fibroblasts and melanocytes.Methods:Discarded foreskin tissues were collected from 10 healthy children aged from 3 to 12 years after circumcision surgery in the First Affiliated Hospital of Kunming Medical University from June 2021 to December 2021. After epidermis-dermis separation, selective culture was performed to isolate keratinocytes, fibroblasts, and melanocytes. According to the pre-experiment results, the above three types of cells were irradiated with 440 - 450 nm blue light at doses of 0, 5, 10, 20, 30, and 40 J/cm 2, and then continued to be cultured for 0, 6, 24, and 48 hours. Cell counting kit 8 (CCK8) assay was performed to evaluate cellular proliferative activity at each time point, enzyme-linked immunosorbent assay (ELISA) to detect levels of interleukin (IL) -18, IL-33, nerve growth factor (NGF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by keratinocytes, as well as levels of IL-33 and keratinocyte growth factor (KGF) secreted by fibroblasts, NaOH lysis method to determine melanin synthesis rates in melanocytes, and Western blot analysis to determine the relative expression of tyrosinase (TYR), tyrosine-related protease 1 (TRP-1) and dopachrome isomerase (DCT) in melanocytes. Two-way analysis of variance was used to analyze group effects, time effects and interaction effects. Results:After irradiation with blue light, the cellular proliferative activity significantly differed among different doses of blue light irradiation groups and different time points in keratinocytes ( Ftime = 516.20, Fdose = 421.20, Finteraction = 25.05, all P < 0.003), fibroblasts ( Ftime = 129.30, Fdose = 477.80, Finteraction = 10.91, all P < 0.003), and melanocytes ( Ftime = 77.61, Fdose = 138.70, Finteraction = 3.50, all P < 0.003) ; immediately after irradiation, the proliferative activity of keratinocytes and fibroblasts was significantly lower in the 20 - 40 J/cm 2 blue light group than in the 0 J/cm 2 blue light group (all P < 0.003), and the proliferative activity of melanocytes was significantly higher in the 5 J/cm 2 blue light group than in the 0 J/cm 2 blue light group ( P < 0.003) ; the proliferative activity of the 3 types of cells showed decreasing trends with the increase of blue light irradiation doses and culture time. ELISA showed that the concentrations of IL-18, IL-33, NGF, and GM-CSF secreted by keratinocytes, as well as the concentrations of IL-33 and KGF secreted by fibroblasts, tended to increase with the increase of blue light irradiation doses and culture time. The melanin synthesis rates in melanocytes significantly differed among different doses of blue light irradiation groups and different time points ( Ftime = 833.50, Fdose = 249.40, Finteraction = 81.38, all P < 0.003) ; during 0 - 24 hours after blue light irradiation, the melanin synthesis rates tended to increase with the increase of blue light irradiation doses and time; during 24 - 48 hours, the melanin synthesis rates showed decreasing trends with the increase of blue light irradiation doses and culture time compared with that at 24 hours after irradiation; 24 hours after irradiation, the melanin synthesis rates were significantly higher in the 5, 10, 20, 30 and 40 J/cm 2 blue light groups (159.50% ± 10.88%, 218.76% ± 8.49%, 333.72% ± 7.72%, 393.29% ± 6.00%, 427.21% ± 8.39%, respectively) than in the 0 J/cm 2 blue light group (102.29% ± 6.57%, all P < 0.003). The relative expression of TYR ( Ftime = 67.94, Fdose = 28.99, Finteraction = 3.71, all P < 0.003), TRP-1 ( Ftime = 21.73, Fdose = 8.38, both P < 0.003) and DCT ( Ftime = 34.51, Fdose = 11.79, both P < 0.003) in melanocytes significantly differed among different doses of blue light irradiation groups and different time points, and tended to increase with the increase of blue light irradiation doses and culture time. Conclusion:Blue light irradiation at doses of 5 - 40 J/cm 2 could inhibit the proliferative activity of human skin keratinocytes, fibroblasts, and melanocytes, and the inhibitory effect tended to increase with the increase of blue light irradiation doses, except an enhancing effect on the proliferative activity of melanocytes observed immediately after irradiation with blue light at 5 J/cm 2; additionally, blue light irradiation at 5 - 40 J/cm 2 could enhance the expression of melanin synthesis-related enzymes in melanocytes, and increase the melanin synthesis rate in melanocytes over a short period of time.

Objective:To explore changes in high-risk sexual behaviors and associated factors in HIV-infected men who have sex with men (MSM) in industrial workers, and provide evidence for designing behavioral interventions for this population.Methods:In this observational study, HIV-infected MSM were recruited in industrial workers using convenient sampling during August to September 2021. The sample size was estimated to be 530. A questionnaire was used and combined with routine follow-up to collect socio-demographic characteristics, high-risk sexual behaviors, partner notification, viral load testing and history of sexually transmitted diseases before and after diagnosis of HIV infection. The χ2 test was used to analyze the changes in high-risk sexual behaviors before and after diagnosis and logistic regression was conducted to identify factors associated with high-risk sexual behaviors. Results:A total of 560 HIV-infected MSM in industrial workers were recruited in this study. Of whom, 32.1% (180/560) had unprotected anal intercourse (UAI) within 12 months after diagnosis . The proportions of those having UAI with casual, commercial and regular same-sex partners significantly decreased from 73.4% (381/519), 75.1% (187/249) and 69.5% (207/298) within 12 months before diagnosis to 36.2% (146/403), 40.2% (86/214) and 34.2% (67/196) within 12 months after diagnosis , respectively. Educational level of college or above (a OR=0.41, 95% CI:0.23-0.71), passive anal sex (a OR=0.40, 95% CI:0.19-0.85), both active and passive anal sex after diagnosis (a OR=0.40, 95% CI:0.20-0.83) and no unprotected oral sex (a OR=0.02, 95% CI:0.01-0.05) were negatively associated with UAI within 12 months after diagnosis. Whereas, not considering necessary to use condom consistently after having repeated undetectable viral load (a OR=3.02, 95% CI:1.37-6.69) was positively associated with UAI within 12 months after diagnosis. Conclusions:Compared with that before diagnosis of HIV infection, although the prevalence of UAI seemed to decrease in HIV-infected MSM in industrial workers after diagnosis, nearly one third of them had high-risk sexual behaviors. Therefore, relevant interventions should be strengthened to reduce high-risk sexual behaviors.