Non-alcoholic fatty liver disease （NAFLD） is a chronic liver disease closely related to metabolism， which is mainly characterized by abnormal lipid deposition in hepatocytes. In recent years， with the increasing prevalence of obesity and metabolic syndrome， NAFLD has become one of the most common chronic diseases in the world. The pathogenesis of NAFLD is complex and varied， involving the cross-regulation of multiple signaling pathways such as glucose-lipid metabolism， oxidative stress， and inflammation. The TLR4 signaling pathway plays a key role in the development and progression of NAFLD， and abnormal activation of this pathway accelerates the deterioration of NAFLD by promoting the release of pro-inflammatory cytokines， inducing oxidative stress， and exacerbating insulin resistance. Studies have shown that traditional Chinese medicine （TCM） can regulate the TLR4 signaling pathway to alleviate the symptoms and pathological features of NAFLD. The present review summarizes the experimental research progress in the TCM regulation of the TLR4 signaling pathway in treating NAFLD in the past 5 years， covering a wide range of TCM active ingredients （such as polysaccharides， terpenoids， alkaloids， flavonoids） and compound prescriptions. The active ingredients and compound prescriptions of TCM can effectively ameliorate lipid metabolism disorders， reduce insulin resistance， regulate intestinal flora， and inhibit inflammation and oxidative stress by regulating the TLR4 signaling pathway via multiple targets and pathways， thus slowing down the progression of NAFLD. Through in-depth analysis of the pathological mechanisms of NAFLD and exploration of the potential of TLR4 signaling pathway as a therapeutic target， we can provide theoretical support for the application of TCM in the treatment of NAFLD， as well as new perspectives and directions for future clinical research and new drug development， thereby promoting the innovation and development of therapeutic strategies for NAFLD.

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*

To explore the chemical constituents of Ecballium elaterium and their cytotoxicity, this study employed multiple chromatographic techniques including normal-phase silica gel, MCI, octadecylsilyl(ODS), Sephadex LH-20 gel, and semi-preparative liquid chromatography for compound isolation from its active fraction. A total of 12 compounds were obtained, and they were identified according to the analysis of a variety of spectral data and literature comparison as 24Z-20,27-dihydroxy-16α,23α-epoxy-cucurbita-2-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside(1), cucurbitacin R(2), cucurbitacin B(3), cucurbitacin D(4), cucurbitacin I(5), cucurbitacin L(6), dehydrodiconiferyl alcohol(7), 3-hydroxy-4-methoxycinnamic acid(8), ferulaic acid(9), p-coumaric acid(10), rutin(11), and lariciresinol-4'-O-β-D-glucoside(12), among which compound 1 was a new compound. Compounds 2-6 had strong cytotoxicity against human lung carcinoma A549 cells with the IC_(50) values of(0.48±0.09),(0.03±0.002),(0.13±0.03),(0.87±0.14),(0.15±0.03) μmol·L~(-1), respectively, which were stronger than the positive control doxorubicin \[IC_(50)=(3.92±1.60) μmol·L~(-1)\].
Humans ; Drugs, Chinese Herbal/toxicity* ; Cell Line, Tumor ; Cucurbitaceae/chemistry* ; Cell Survival/drug effects*

OBJECTIVE To investigate the effects and mechanism of Yiqi huoxue decoction （YQHX） on lumbar disc herniation in rats. METHODS Rats were randomly divided into sham operation group， model group， NF-κB inhibitor group （QNZ group， 1 mg/kg）， YQHX group （9.1 g/kg） and combination group （YQHX+QNZ group， the same dose as each single drug group）， with 10 rats in each group. Except for sham operation group， lumbar disc herniation model of rats was induced in other groups； administration groups were given QNZ intraperitoneally or/and YQHX intragastrically， once a day， for 8 consecutive weeks. The severity of intervertebral disc herniation was evaluated in each group； the pathological changes of intervertebral discs and the changes of autophagy of nucleus pulposus cells were all observed； the level of tumor necrosis factor-α （TNF-α） in serum， and the ratios of Bcl-2/adenovirus E1B interacting protein 3 （BNIP3） and Beclin-1 positive cells in intervertebral disctissues were detected； the phosphorylation of nuclear factor-κB （NF-κB） p65， the expressions of tumor necrosis factor receptor- associated factor-2 （TRAF-2）， TRAF-3， BNIP3 and LC3B protein， and mRNA expressions of NF-κB p65， LC3B， p62，BNIP3 and Beclin-1 were determined. RESULTS Compared with model group， Pfirrmann grading score decreased significantly，the pathological injury of intervertebral disc tissue was relieved in YQHX group； the number of autophagosomes in nucleus pulposus cells increased； serum level of TNF-α and mRNA expression of p62 in intervertebral disc tissue decreased significantly； the ratios of BNIP3 and Beclin-1 positive cells， the phosphorylation of NF-κB p65， the expressions of TRAF-2， TRAF-3， BNIP3 and LC3B protein as well as the mRNA expressions of NF- κB p65， LC3B， BNIP3 and Beclin-1 decreased significantly in intervertebral disc tissues （P＜0.05）. The changes of above indexes in YQHX group were reversed partly in YQHX+QNZ group. CONCLUSIONS YQHX promotes the elevation of autophagy level of intervertebral discs， slows down the inflammatory response and the progression of lumbar disc herniation by activating the NF-κB signaling pathway.

Objective:To investigate the effects of recombinant human metallothionein-Ⅲ (rh-MT-Ⅲ) combined with wound dressing on wound healing of full-thickness skin defects in mice.Methods:This study was an experimental study. Twenty-four half male and half female 6 weeks old Institute of Cancer Research mice were taken, and two symmetrical round full-thickness skin defect wounds were prepared on the back of each mouse. The mice were stratified and randomly divided into normal saline group, dressing group, rh-MT-Ⅲgroup (applying the corresponding solution on the wounds), and combined treatment group (applying a mixture of rh-MT-Ⅲ and wound dressing on the wounds) according to sex and body weight, with 6 mice in each group. From 1 to 7 d after injury, all mice were observed daily for changes in activity, diet, and fur growth, their body weights and wound areas were recorded, and the relative wound area percentages were calculated. On 7 d after injury, the wound tissue of mice was taken for hematoxylin-eosin staining to observe the newborn granulation tissue, for Masson staining to observe collagen fiber formation, and for immunofluorescence staining to detect cell proliferation (denoted as Ki67 relative fluorescence intensity) and cell apoptosis (denoted as TdT-mediated dUTP nick end labeling (TUNEL) relative fluorescence intensity). The sample size in the above experiments was 6.Results:There were no abnormalities in activity, diet, or fur growth in the 4 groups of mice within 7 d after injury. There were no statistically significant differences in the overall comparison of the body weights of mice in the 4 groups from 1 to 7 d after injury ( P>0.05). The relative wound area percentages of mice in combined treatment group were significantly lower than those in normal saline group and rh-MT-Ⅲ group on 2, 3, 4, 5, 6, and 7 d after injury ( P<0.05), and the relative wound area percentages of mice in combined treatment group were significantly lower than those in dressing group on 3, 4, 5, 6, and 7 d after injury ( P<0.05). The relative wound area percentages of mice in dressing group on 6 and 7 d after injury and in rh-MT-Ⅲ group on 7 d after injury were significantly lower than those in normal saline group ( P<0.05). On 7 d after injury, a large number of capillaries and fibroblasts could be seen in wound tissue of mice in combined treatment group, and the growth of new epithelial tissue at the upper edge of the wound was better than that of the other three groups; the collagen fibers in the wound tissue of mice in combined treatment group had higher degree of density and arrangement in a more orderly manner than those of the other three groups. On 7 d after injury, the Ki67 relative fluorescence intensity in the wound tissue of mice in dressing group, rh-MT-Ⅲ group, and combined treatment group was (289±35)%, (197±17)%, and (389±56)%, which was significantly higher than (100±15)% in normal saline group, respectively ( P<0.05), and the Ki67 relative fluorescence intensity in the wound tissue of mice in combined treatment group was significantly higher than that in dressing group and rh-MT-Ⅲ group, respectively (with both P values <0.05). On 7 d after injury, the TUNEL relative fluorescence intensity in the wound tissue of mice in dressing group, rh-MT-Ⅲ group, and combined treatment group was (55.5±5.7)%, (66.7±8.0)%, and (20.0±2.2)%, which was significantly lower than (100.0±12.9)% in normal saline group, respectively ( P<0.05), and the TUNEL relative fluorescence intensity in the wound tissue of mice in combined treatment group was significantly lower than that in dressing group and rh-MT-Ⅲ group, respectively (with both P values <0.05). Conclusions:rh-MT-Ⅲ combined with wound dressing can promote the growth of granulation tissue around the wound as well as collagen deposition, increase the cell proliferation vitality, reduce cell apoptosis, and promote the re-epithelialization of skin at the edge of the wounds, thus accelerating the healing of full-thickness skin defect wounds in mice.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective:To investigate the effect of flow cytometric minimal residual disease(MRD)detection at different time points during AML chemotherapy on prognosis.Methods:130 adult primary AML patients diagnosed and standardized with chemotherapy from March 2018 to March 2022 were retrospectively analyzed,MRD was detected by flow cytometry,Kaplan-Meier curves was used for survival analysis and log-rank test was used for variance analysis,and univariate and multifactor influencing patient survival with COX proportional risk regression model analysis.Cumulative incidence rate(CIR)analysis with competing risk model and variance analysis using Fine-Gray.Results:There were 81 CR1,26 CR2,14 PR,and 9 NR patients in 130 patients.OS of the CR1 group was higher than that in the CR2,PR,and NR groups.OS of the CR2 group was higher than that in the PR group,but there was no statistically difference compared to the NR group.There was no statistically difference in OS between the PR and NR groups.107 patients in CR1 and CR2 were grouped according to MRD detected by flow cytometry,and after the first induction chemotherapy,for patients in the MRD-and MRD+groups,the 4-year expected RFS rates were 65.3％and 27.9％respectively,the 4-year expected OS rates were 58.7％and41.4％respectively,and the 4-year expected CIR were 34.7％and 69.7％respectively,with statistically significant differences between 2 groups(x2=6.639,P=0.010;x2=6.131,P=0.013 and x2=6.637,P=0.010).After the second chemotherapy,for patients in the MRD-and MRD+groups,the 4-year expected RFS rates were 50.8％and 37.9％respectively,the 4-year expected OS rates were 49.2％and 44.5％respectively,and the 4-year expected CIR were 49.2％and 59.5％respectively,with no statistically significant differences between 2 groups(x2=1.475,P=0.225;x2=2.432,P=0.119 and x2=1.416,P=0.234).During consolidation therapy,for patients in the MRD-and MRD+groups,the 4-year expected RFS rates were 51.9％and 29.6％respectively,the 4-year expected OS rates were 67.5％and 24.6％respectively,and the 4-year expected CIR were 48.1％and 70.4％respectively,with statistically significant differences between 2 groups(x2=20.982,P＜0.001;x2=17.794,P＜0.001 and x2=19.879,P＜0.001).For patients with MRD-at all three time points and positive at either time point,the 4-year expected RFS rates were 69.9％and 33.3％respectively,the 4-year expected OS rates were 59.1％and 44.7％respectively,and the 4-year expected CIR were 30.1％and 65.1％respectively,with statistically significant differences between 2 groups(x2=7.367,P=0.007;x2=6.042,P=0.014 and x2=7.662,P=0.006).Univariate analysis showed that karyotype at high risk of chromosome was an unfavorable factor affecting patients'RFS and OS,while 2 cycles of induction chemotherapy achieved CR,MRD-after the first induction chemotherapy and MRD-after the second induction chemotherapy was a protective factor affecting patients'RFS and OS.MRD-during consolidation therapy and MRD-at all three time points were all protective factors affecting patients'RFS,OS and CIR.Multivariate analysis showed that induction chemotherapy for 2 cycles achieved CR was a protective factor affecting patients'RFS and CIR,and MRD-during consolidation therapy was a protective factor affecting patients'RFS,OS and CIR.Conclusion:Early achievement of CR and MRD-in adult AML patients,especially MRD-during consolidation therapy,is a marker of good prognosis,and flow cytometry is the most commonly used method for MRD detection in AML patients.

Aim To clarify the differential proteins of mammary tissues in Xihuang pills(XHP)against hy-perplasia of mammary glands(HMG)based on quanti-tative proteomics technology and validate them,and to explore the mechanism of action.Methods SD rats were randomly divided into blank group,model group and XHP group,with 10 rats in each group.Except for the blank group,estrogen and progesterone were injec-ted intramuscularly to establish a rat model of mamma-ry hyperplasia for 30 d.After XHP was administered for 14 d,the rats in each group were observed to have morphological changes in the apparent morphology of the mammary tissues,and pathological changes in the mammary tissues were stained with hematoxylin-eosin staining(HE),and the differentially expressed pro-teins(DEPs)in the groups were screened by quantita-tive proteomics technology and subjected to bioinforma-tics analysis,and Western blot to verify the key DEPs.Results Compared with the model group,the appar-ent pathological morphology of the XHP group was sig-nificantly improved,the diameter of the nipple height of the rats was significantly reduced(P＜0.01),and the degree of histopathology was significantly allevia-ted.Quantitative proteomics identified 4,299 DEPs in mammary tissue,and bioinformatics analysis of 14 DEPs with consistent changes between the XHP group and the blank group relative to the model group re-vealed that they were related to the regulation of mus-cular systemic processes,regulation of muscle contrac-tion,DNA replication,and pre-initiation of DNA repli-cation.Western blot results showed that,compared with the model group,rat mammary tissue of the XHP group showed significantly lower levels of ACLY and ALDOC protein expression levels were significantly re-duced and BIN1 protein expression levels were signifi-cantly increased(P＜0.01).Conclusions XHP may exert its anti-mammary hyperplasia effect through the regulation of BIN1,ACLY and ALDOC protein lev-els,the regulation of DNA replication,the regulation of pre-initiation of DNA replication and muscular sys-temic processes,and the regulation of muscle contrac-tion.