A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.

Objective:To study the the mechanism of action of Huanglong Mixture in the treatment of cough variant asthma (CVA) in children based on the IL-4/signal transduction and activator of transcription 6 (STAT6) signaling pathway using network pharmacology methods, molecular docking techniques, and in vitro cell experiments.Methods:The components and targets of various TCM components in Huanglong Mixture were searched in TCMSP database, HERB database and literature, and the disease targets of CVA were found in Gene Cards database, OMIM database, DrugBank database and PharmGkb database. The STRING database was used to construct the protein-protein interaction network, and Cytoscape 3.9.1 was used for topology analysis to screen out the core targets. The disease-drug-component-target network was constructed to screen out the core components. The KEGG enrichment analysis and GO enrichment analysis of the intersection targets were performed using Metascape software. PDB protein database, PubChem, Autodock and R language were used for molecular docking verification of core targets and core drug components. Finally, rat primary airway smooth muscle cells were cultured, modeled with interleukin-4 (IL-4), and p-STAT6 expression in the cytoplasm and nucleus was detected by Western blot.Results:A total of 122 effective components were obtained, including quercetin, kaempferol, luteolin and so on. The core targets included JUN, ESR1, TP53, MYC, HIF1, etc. GO enrichment analysis involved biological processes such as response to external stimuli, response to oxygen levels, positive regulation of protein phosphorylation, and regulation of cellular stress response. KEGG enrichment analysis showed that the main pathways of Huanglong Mixture in treating CVA included advanced glycation end product-glycation end product receptor (AGE-RAGE) signaling pathway, phosphatidylinositol-3-kinase-protein kinase B (PI3K-Akt) signaling pathway, tumor necrosis factor (TNF) signaling pathway, Janus kinase/signal transduction activation factor (JAK-STAT) signaling pathway. Molecular docking found that the core targets and core drug components had good combination. Cell experiments also confirmed that Huanglong Mixture could inhibit p-STAT6 entering the nucleus.Conclusions:The effective components and targets of Huanglong Mixture in the treatment of CVA are successfully predicted. The mechanism of Huanglong Mixture in the treatment of children with CVA may be related to the inhibition of IL-4/STAT6 signaling pathway.

Based on the literature study,the thoughts and possible therapeutic mechanism in treating male infertility from the perspective of spleen and kidney by regulating intestinal flora were explored.Disturbance of intestinal flora is one of the important factors leading to the development of male infertility,and the spleen and kidney have certain similarities to intestinal flora in the physiological function and pathological changes.Moreover,tonifying the kidney and strengthening the spleen can regulate the intestinal flora by fostering the growth of beneficial bacteria,inhibiting the reproduction of pathogenic bacteria,and protecting the barrier of the intestinal mucosa.Therefore,the possible therapeutic mechanisms in treating male infertility with the prescriptions for tonifying the kidney and strengthening the spleen to regulate intestinal flora are as follows:inhibiting the expression of inflammatory factors to reduce the inflammatory reaction of testicular tissues;improving the antioxidant capacity to alleviate the damage of spermatozoa caused by oxidative stress,and improving the bad mood to alleviate the impact of psychological stress on the reproductive system.The exploration of the thoughts for treating male infertility from the perspective of spleen and kidney by regulating intestinal flora may provide a new entry point for modern Chinese medicine clinical treatment of male infertility.

BACKGROUND:Obesity and its relevant chronic inflammation are important risk factors for inducing type 2 diabetes.This inflammatory response will further involve skeletal muscle,leading to an increase in catabolic and autophagic fluxes in skeletal muscle.Aerobic exercise is the mainstream mode of exercise in the prevention and treatment of type 2 diabetes,and may also has a certain protective effect on skeletal muscle. OBJECTIVE:To explore the effects and regulatory mechanisms of aerobic exercise on glucolipid metabolism,skeletal muscle inflammation and autophagy in type 2 diabetic rats. METHODS:Animal models of type 2 diabetes were established in rats by 8-week high-fat feeding combined with streptozotocin injection,and the experimental rats were then divided into normal control group,normal exercise group,diabetic control group and diabetic exercise group.The exercise group performed 4 weeks of aerobic exercise(16 m/min,60 min/d,5 d/wk).The levels of blood glucose,high-density lipoprotein,low-density lipoprotein and triglyceride in serum were measured by an automated biochemical analyzer.Serum insulin level was determined using enzyme-linked immunosorbent assay and the insulin resistance index and area under the glucose metabolism curve were calculated.The levels of interleukin 6 and tumor necrosis factor α in skeletal muscle were measured by enzyme-linked immunosorbent assay after 4 weeks of aerobic exercise,and the expression levels of forkhead box protein O3(FoxO3),LC3 and p62 in skeletal muscle were measured by western blot assay. RESULTS AND CONCLUSION:The area under the glucose tolerance curve and insulin resistance index both increased significantly in type 2 diabetic rats(P<0.001,P=0.025),and aerobic exercise significantly reduced the area under the glucose tolerance curve and insulin resistance index in the normal exercise group(P<0.001,P=0.038)and diabetic exercise group(P<0.001,P=0.004).Serum high-density lipoprotein significantly decreased(P=0.030),and low-density lipoprotein and triglyceride(P=0.027,P=0.014)levels significantly increased in the diabetic control group compared with the normal control group.Aerobic exercise significantly reduced triglyceride and low-density lipoprotein levels in the normal exercise group(P=0.019,P=0.008)as well as triglyceride levels in the diabetic exercise group(P=0.022).Both interleukin-6 and tumor necrosis factor α levels were significantly increased in the skeletal muscle of type 2 diabetic rats compared with the normal control group(P<0.001,P=0.007),and aerobic exercise significantly reduced tumor necrosis factor α levels in the diabetic exercise group(P=0.017).The LC3-Ⅱ/LC3-I was significantly increased in the skeletal muscle of type 2 diabetic rats compared with the normal control group.Aerobic exercise significantly increased the LC3-Ⅱ/LC3-I in the normal exercise group(P<0.001)and decreased the LC3-Ⅱ/LC3-I,FoxO3 and p62 protein expression levels in the diabetic exercise group(P=0.026,P=0.050,P=0.048).To conclusion,type 2 diabetes model established by high-fat feeding combined with streptozotocin injection has obvious glycolipid metabolism disorder,and leads to inflammatory response and excessive activation of autophagy in skeletal muscle.Aerobic exercise can improve glycolipid metabolism,reduce local inflammation in skeletal muscle and inhibit autophagy,and finally play a protective role in skeletal muscle.

Objective : To investigate the effect of miR-141-3p on LPS induced A549 cell injury by targeting high mobility group protein 1 (HMGB1) ． Methods : A549 cells derived from type Ⅱ alveolar epithelial cells were taken as the study object，miR-141-3p mimics，mimics NC，HMGB1 gene overexpression plasmid (pcDNA3. 1-HMGB1) and empty Vector were transfected into A549 cells respectively or co-transfected，then 10 μg / ml LPS was used for 24 h．Cell proliferation activity was detected by cell counting kit-8 ( CCK-8) ．The activity of lactate dehydrogenase ( LDH) in the supernatant of cell culture was detected by colorimetry．The apoptosis level of each group was detec- ted by flow cytometry．The levels of interleukin (IL) -1 β , IL-6 and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay (Elisa) ．Dual luciferase reporter gene assay verified the targeted regulatory relationship between miR-141-3p and HMGB1 . Results : After treatment with LPS ，the proliferative activity of A549 cells and the expression level of miR-141-3p decreased ( P ＜0. 05 ) ，the apoptosis rate increased ( P < 0. 05) ，the levels of IL-1 β , IL-6，TNF-α and the activity of LDH in supernatant increased (P＜0. 05) ．Overex- pression of miR-141-3p increased the proliferation activity of A549 cells treated with LPS (P ＜0. 05 ) ，and de- creased the apoptosis rate and the levels of IL-1 β , IL-6，TNF-α in cells and LDH activity in supernatant (P < 0. 05) ．However，overexpression of HMGB1 gene could reverse the ameliorative effect of miR-141-3p on LPS-in- duced A549 cell injury．Dual luciferase reporter gene experiment confirmed that HMGB1 was the downstream target gene of miR-141-3p． Conclusion miR-141-3p can inhibit LPS-induced apoptosis，reduce the expression level of inflammatory factors，and improve the damage of A549 cells，which may be related to the targeted regulation of HMGB1 expression.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Tranexamic acid is widely used in joint orthopedic surgery.At the same time,it has high safety and few adverse drug reactions.It can effectively improve intraoperative bleeding and promote early functional recovery of patients.This article reviews the mode of administration,safe dose,administration time and adverse drug reactions of tranexamic acid in the perioperative period of joint replacement and arthroscopic surgery,in order to provide reference for the clinical application of tranexamic acid.

AIM To establish the HPLC characteristic chromatogram of Baqi Rougan Decoction reference sample,and to investigate its quantitative transmission laws.METHODS The contents of calycosin 7-O-glucoside,hesperidin,rosmarinic acid,curcumenol and nystose were determined.The transfer rates of decoction piece-aqueous decoction-reference sample were calculated,after which the paste-forming rate and pH value were recorded.RESULTS There were sixteen characteristic peaks in fifteen batches of reference samples with the similarities of 0.90,nine of which were identified.The average transfer rates of nystose and calycosin 7-O-glucoside in the reference sample were(83.14±6.25)%and(77.81±8.31)%,while those of rosmarinic acid and curcumenol in the aqueous decoction-reference sample were(81.71±6.27)%and(72.16±5.91)%,along with the average paste-forming rate and pH value of(38.91%±1.46%)and 5.13±0.08,respectively.CONCLUSION This stable and feasible method can provide a reference for the selection of preparation process and evaluation of key chemical properties for Baqi Rougan Decoction.

【Objective】 To explore the expression of PCDH9 loss in regulating cell cycle and promoting tumor progression. 【Methods】 The clinical records of 127 cases of prostate cancer treated during 2018 and 2023 were collected, including 87 paraffin tissue samples from the G4-5 group and 40 from the G1-3 group. The expressions of PCDH9, p53, Rb and STAT3 were detected with immunohistochemical staining, and the relationship between their expressions and clinicopathological characteristics was analyzed. 【Results】 The expression deletion rate of PCDH9 in prostate cancer tissues in G4-5 group (44.8% vs.7.5%) was significantly higher than that in G1-3 group (P<0.001). The positive expression rates of p53 and STAT3 were 34.5% and 89.7%, respectively, and the expression loss rate of Rb was 27.6% in G4-5 group. The expression loss rates of PCDH9 and Rb were associated with neuroendocrine-like histological morphology, nerve invasion and vascular invasion (P<0.05). In G4-5 group of prostate cancer, PCDH9 expression was positively correlated with the expressions of p53 (r=0.345, P<0.05), Rb (r=0.503, P<0.05) and STAT3 (r=0.224, P<0.05). 【Conclusion】 PCDH9 is prone to loss of expression in high-group prostate cancer tissues, especially in cases with neuroendocrine-like histological morphology, which may regulate the cell cycle through the STAT3 signaling pathway, thereby promoting tumor progression.