This study aims to explore the mechanism of Huanglian Jiedu Decoction(HJD) in treating acute liver injury(ALI) in the mouse model of sepsis induced by lipopolysaccharide(LPS). Fifty-four male C57BL/6 mice were randomized into six groups: blank group, model group, low-, medium-, and high-dose group HJD, and dexamethasone group. The mouse model of sepsis was established by intraperitoneal injection of LPS after 7 days of gavage with HJD, and dexamethasone(0.2 mL) was injected intraperitoneally 1.5 h after modeling. The murine sepsis score(MSS) was recorded 12 h after modeling. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver tissue and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the serum were measured by ELISA. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of the mouse liver. The content of light chain 3 of microtubule-associated protein 1(LC3) was detected by immunofluorescence, and that of sirtuin 1(SIRT1) was detected by immunohistochemistry. The mRNA levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), LC3, and P62 were detected by RT-PCR. Western blot was employed to determine the protein levels of AMPK, p-AMPK, and SIRT1 in the liver tissue. The results showed that compared with model group, drug interventions decreased the MSS and liver injury indicators, lowered the levels of inflammatory cytokines, improved the liver tissue structure, upregulated the protein levels of of p-AMPK/AMPK and SIRT1 and the mRNA levels of AMPK and LC3, and downregulated the mRNA level of P62. To sum up, HJD can regulate the autophagy level and reduce inflammation to ameliorate acute liver injury in septic mice by activating the AMPK/SIRT1 autophagy pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Sirtuin 1/genetics* ; Male ; Mice ; Sepsis/metabolism* ; Mice, Inbred C57BL ; Autophagy/drug effects* ; AMP-Activated Protein Kinases/genetics* ; Liver/metabolism* ; Humans ; Signal Transduction/drug effects* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/genetics*

Objective To investigate the therapeutic effect of Huatan Jieyu Anshen Decoction(mainly with the actions of resolving phlegm,relieving depression and calming mind)combined with abdominal vibration tuina manipulations on chronic insomnia in the elderly.Methods Ninety-four cases of elderly patients with chronic insomnia of phlegm-heat harassing the interior type were randomly divided into the observation group and the control group,with 47 cases in each group.The control group was given Huatan Jieyu Anshen Decoction orally,while the observation group was given oral use of Huatan Jieyu Anshen Decoction combined with abdominal vibration tuina manipulations.The course of treatment for the two groups lasted for 4 weeks.Before and after the treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,Pittsburgh Sleep Quality Index(PSQI)score,Athens Insomnia Scale(AIS)score,Fatigue Scale-14(FS-14)score,World Health Organization Quality-of-Life Brief Scale(WHOQOL-BREF)score,and the serum levels of melatonin(MT),dopamine(DA),and cortisol(CORT).After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 97.88%(46/47),while that of the control group was 87.23%(41/47),and the intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the observation group was superior to that of the control group(P＜0.01).(2)After treatment,the scores of primary and secondary TCM symptoms in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of the scores of primary and secondary TCM symptoms in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the PSQI scores,AIS scores,and FS-14 scores in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the WHOQOL-BREF scores were significantly increased compared with those before treatment(P＜0.05).The decrease of the PSQI scores,AIS scores and FS-14 scores as well as the increase of the WHOQOL-BREF scores in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the serum MT level of both groups was significantly higher than that before treatment(P＜0.05),and the serum DA and CORT levels were significantly lower than those before treatment(P＜0.05).The increase in serum MT level and the decrease in serum DA and CORT levels of the observation group were significantly superior to those of the control group(P＜0.01).Conclusion The combined therapy of Huatan Jieyu Anshen Decoction combined with vibration tuina manipulations can achieve satisfactory efficacy in the elderly patients with chronic insomnia of phlegm-heat harassing the interior syndrome.The therapy is effective on regulating the central nervous system of the patients,improving the quality of the sleep,and promoting the relief of fatigue and the enhancement of the quality of life,which has great significance to the enhancement of the overall therapeutic efficacy of insomnia.

ObjectiveThe differential expression of microRNAs （miRNAs） between the active stage and the remission stage of ulcerative colitis （UC） was analyzed by bioinformatics method， and the regulatory relationship was constructed by screening the differentially expressed genes （DEGs）. The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database （GEO）， and the most differentially expressed miRNAs were screened by GEO2R， Excel， and other tools as research objects. TargetScan， miRTarbase， miRDB， STRING， TRRUST， and Matescape databases were used to screen key DEGs， predict downstream transcription factors （TFs）， gene ontology （GO）， and conduct Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor （SOCS1）， phosphorylated transcriptional signal transductor and activator 3 （p-STAT3）， phosphorylated Janus kinase 2 （p-JAK2）， and retinoic acid-associated orphan receptor-γt （ROR-γt）. The expression levels of transforming growth factor-β （TGF-β）， interleukin-17 （IL-17）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in serum were detected by enzyme linked immunosorbent assay （ELISA）. ResultThe GSE48957 dataset was screened from the GEO database， and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation， as well as signaling pathways such as stem cell signaling pathway， IL-17 signaling pathway， and helper T cell 17 （Th17） cell differentiation. The Matescape database was used to screen out 10 key DEGs， among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3， p-JAK2， and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice， up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10， increase the level of anti-inflammatory factors， and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice， inhibit the phosphorylation of STAT3， inhibit the differentiation of CD4⁺ T cells into Th17 cells， reduce the levels of pro-inflammatory factors （IL-17 and IL-6）， and increase the levels of anti-inflammatory factors （TGF-β and IL-10）. As a result， the inflammation of colon mucosa in UC mice was alleviated.

Aim To investigate the promotional effects of neutrophil extracellular traps(NETs)on renal tissue damage and intestinal flora disruption induced by dia-betic kidney disease(DKD)and the potential mecha-nisms.Methods C57BL/6 mice were divided into:control group(NC),DNase Ⅰ control group(DNase Ⅰ)diabetic nephropathy group(DKD),and DNase Ⅰ treated group(DKD+DNase Ⅰ).The pathological changes of mouse kidney were observed by PAS,MAS-SON,and HE staining.The expression and distribu-tion of the relevant proteins of NETs in renal tissue of the mice in each group were observed by immunohisto-chemistry.The expression and distribution of coke-death-related proteins in the kidney tissues of mice in each group were observed by immunohistochemistry.The protein expression of NETs-related indexes,focal death-related indexes and NF-κB signaling pathway-re-lated indexes in kidney tissue of mice in each group were detected by immunoblotting.Results The ex-pression of indicators related to NETs was elevated in the DKD group,and their expression decreased after degradation of NETs by DNase Ⅰ(P＜0.01).Patho-logical staining results showed that the kidneys of DKD mice were structurally abnormal,and the structure was improved after degradation of NETs by DNase Ⅰ.The results of immunohistochemical staining and immunob-lotting showed that the expression of pyroptosis-related proteins in kidney tissues of mice in the DKD group was elevated compared with that in the control group(P＜0.01).NF-κB-related signaling pathway protein expression profile expression rose,and its expression decreased after degradation of NETs by DNase Ⅰ(P＜0.01)Conclusions NETs are generated in diabetic nephropathy and promote the onset of renal focal death and activation of the NF-κB signaling pathway,thereby exacerbating diabetes-induced kidney injury.

The overall health condition of patients significantly affects the diagnosis,treatment,and prognosis of endodontic diseases.A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy,as well as selecting appropriate therapeutic approaches.This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures,improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Objective:To systematically evaluate the methodological quality and reporting quality of randomized controlled tri-als(RCT)on the treatment of BPH with traditional Chinese medicine(TCM),in order to provide some methodological reference for clinical practice and research.Methods:We searched CNKI,VIP,Wanfang Data and PubMed for RCTs on the treatment of BPH with TCM published in China from January 2013 to November 2023.Two researchers screened the literature separately,and evaluated the methodological and reporting quality of the RCTs based on the Cochrane bias risk assessment tool and CONSORT TCM compound.Results:Totally,88 RCTs were included in this study.In terms of methodological quality,according to the Cochrane bias risk assess-ment tool,27 biases in the process of randomization were identified as of low-risk and the other 61 of a certain risk.Among the alloca-tion-related biases deviating from the established interventions,76 were of low risk,10 of a certain risk and 2 of high risk;among the compliance-related biases deviating from the established interventions,76 were of low risk and 12 of a certain risk;among the biases due to missing outcome data,86 were of low risk and 2 of a certain risk,while all the biases due to outcome measurement were of low risk;and among the biases from selective reporting,65 were of low-risk,2 of a certain risk and 21 of high-risk.In terms of reporting quality,according to the evaluation criteria of consort TCM compound,appropriate key words were used in 1 RCT(0.01％),the ran-dom assignment sequence method described in 27(30.68％),the details of assignment limitation given in 5(5.68％),assignment concealment mentioned in 3(3.41％),the blind method and assignment concealment employed in 3(3.41％),fall-offs recorded in 10(11.36％),adverse events reported in 38(43.18％),and limitations of the trials analyzed in 18(20.45％).All the RCTs lacked complete intervention measures,subject flow chart,clinical trial registration and research schemes.Conclusion:At present,the methodological quality and reporting quality of RCTs on the treatment of BPH with TCM are generally low,with the main problems of incomplete experimental designs,lack of detailed description of randomized and blind methods,and insufficient TCM symptom eval-uation of outcome indicators.Researchers should be cautious in adopting and applying the results reported,follow the CONSORT state-ment in design,registration,implement and reporting of the scheme,fully consider the clinical characteristics of TCM in the treatment of BPH,and reasonably design and report the evaluation indicators.

OBJECTIVE: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25-160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 β, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. RESULTS: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 β, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01). CONCLUSIONS The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Chalcone/analogs & derivatives* ; Quinones/pharmacology* ; Pyroptosis/drug effects* ; Caspase 1/metabolism* ; Glucose ; Phosphate-Binding Proteins/metabolism* ; Signal Transduction/drug effects* ; Intracellular Signaling Peptides and Proteins/metabolism* ; Oxygen/metabolism* ; Cytokines/metabolism* ; Gasdermins

Objective To analyze the epidemiological characteristics of pulmonary tuberculosis in the elderly people in Wuhan during 2016-2020, and to provide a basis for formulating effective prevention and control strategies and measures. Methods Using the National Tuberculosis Information Management System, a descriptive statistical analysis was performed on the medical records of elderly (≥60 years old) pulmonary tuberculosis patients registered in Wuhan from 2016 to 2020. Results A total of 9 427 elderly pulmonary tuberculosis patients were registered in Wuhan during 2016-2020, accounting for 32.07% of the total number of registrations in the whole population. The reported incidence rate of tuberculosis in the elderly was significantly higher than that in the total population, and the reported incidence rates in both the elderly and the general population showed declining trends (whole population χ²_trend=216.97, P<0.05, elderly population χ²_trend=153.57, P<0.05). The time distribution showed that more cases occurred from April to November (70.90%). The top three districts with the largest number of registered cases were far urban areas, namely Huangpi District (13.81%), Xinzhou District (11.55%), and Jiangxia District (9.82%). The ratio of male to female with pulmonary tuberculosis in elderly patients was 2.85:1. Among the elderly pulmonary tuberculosis, the most registered cases were in the age group of 60 ~ years old, followed by 65 ~ years old. The proportion of smear-positive in elderly patients with pulmonary tuberculosis retreatment was 16.83%. Conclusion From 2016 to 2020, the epidemic situation of elderly pulmonary tuberculosis showed a downward trend in Wuhan. However, the elderly population with tuberculosis registrations still accounted for a relatively high proportion of the total population. According to the epidemiological characteristics of pulmonary tuberculosis among the elderly, the city should carry out tuberculosis prevention and control work in a timely, appropriate and focused manner.

This study aimed to investigate the effect and molecular mechanism of sinomenine on proliferation, apoptosis, metastasis, and combination with inhibitors in human hepatocellular carcinoma HepG2 cells and SK-HEP-1 cells. The effect of sinomenine on the growth ability of HepG2 and SK-HEP-1 cells were investigated by CCK-8 assay, colony formation assay, and BeyoClick~(TM) EdU-488 staining. The effect of sinomenine on DNA damage was detected by immunofluorescence assay, and the effect of sinomenine on apoptosis of human hepatocellular carcinoma cells was clarified by Hoechst 33258 staining and CellEvent~(TM) Cystein-3/7Green ReadyProbes~(TM) reagent assay. Cell invasion assay and 3D tumor cell spheroid invasion assay were performed to investigate the effect of sinomenine on the invasion ability of human hepatocellular carcinoma cells in vitro. The effect of sinomenine on the regulation of protein expression related to the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/signal transducer and activator of transcription 3(STAT3) signaling pathway in HepG2 and SK-HEP-1 cells was examined by Western blot. Molecular docking was used to evaluate the strength of affinity of sinomenine to the target cysteinyl aspartate specific proteinase-3(caspase-3) and STAT3, and combined with CCK-8 assay to detect the changes in cell viability after combination with STAT3 inhibitor JSI-124 in combination with CCK-8 assay. The results showed that sinomenine could significantly reduce the cell viability of human hepatocellular carcinoma cells in a concentration-and time-dependent manner, significantly inhibit the clonogenic ability of human hepatocellular carcinoma cells, and weaken the invasive ability of human hepatocellular carcinoma cells in vitro. In addition, sinomenine could up-regulate the cleaved level of poly ADP-ribose polymerase(PARP), a marker of apoptosis, and down-regulate the protein levels of p-Akt, p-mTOR, and p-STAT3 in human hepatocellular carcinoma cells. Molecular docking results showed that sinomenine had good affinity with the targets caspase-3 and STAT3, and the sensitivity of sinomenine to hepatocellular carcinoma cells was diminished after STAT3 was inhibited. Therefore, sinomenine can inhibit the proliferation and invasion of human hepatocellular carcinoma cells and induce apoptosis, and the mechanism may be attributed to the activation of caspase-3 signaling and inhibition of the Akt/mTOR/STAT3 pathway. This study can provide a new reference for the in-depth research and clinical application of sinomenine and is of great significance to further promote the scientific development and utilization of sinomenine.
Humans ; Carcinoma, Hepatocellular/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; Caspase 3/metabolism* ; Liver Neoplasms/genetics* ; Molecular Docking Simulation ; Sincalide/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Hep G2 Cells ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

Objective: To analyze the difference of application methods and effects of local flap in small and medium-sized defects of different aesthetic subunits of nose, in order to provide reference for clinical work. Methods: A retrospective analysis was made on 59 patients with external nasal masses and scars who underwent surgical treatment in the Department of Aesthetic Plastic Surgery of the Affiliated Hospital of Qingdao University from July 1, 2021 to January 30, 2022, including 27 females and 32 males, aged 15 to 69 years. Using Likert scale, the repair methods and effects of local flap for nasal soft tissue defects were evaluated and summarized from three aspects of texture, flatness and scar concealment. GraphPad Prism 5.0 software was used for data statistics and analysis. Results: The use of skin flaps to repair small and medium-sized areas of the nose could achieve satisfactory results. For patients with different subunits, in terms of skin flatness and scar concealment degree in the operation area, patients' satisfaction with the dorsal and lateral nasal areas was higher than that of the alar and tip areas, respectively (F=6.40, P=0.001; F=10.57, P<0.001). For patients with different skin flap repair methods, the satisfaction of patients with Z-plasty and Dufourmentel skin flap was higher than that of other skin flap repair methods (F=4.38, P=0.002), and the satisfaction of patients with Dufourmentel skin flap was the highest in the degree of scar concealment (F=2.57, P=0.038). Conclusions: In the small and medium-sized defects of the nose, the use of multiple local flaps can achieve good cosmetic effects and functional recovery. The operator should select the appropriate flap repair method according to the characteristics of different aesthetic subunits of the nose.