Stomach exuberance and spleen deficiency are common pathogenesis of many metabolic diseases. Through analyzing the pathogenesis of stomach exuberance and spleen deficiency， it is believed that its essence is stomach heat and spleen deficiency. Stomach heat includes gastrointestinal heat， spleen and stomach damp-heat， and spleen deficiency is divided into deficiency of spleen yin， deficiency of spleen qi ， and deficiency of spleen yang. It is suggested that the metabolic diseases of stomach-exuberance and spleen-deficiency syndrome can be divided into three categories，i.e. stomach-heat and spleen yin-deficiency， stomach-heat and spleen qi-deficiency， and stomach-heat and spleen yang-deficiency， and the main treatment methods are clearing and draining heat， nourishing yin and moistening intestine， clearing dampness and heat， strengthening spleen and qi， clearing dampness and heat， strengthening spleen and warming yang， respectively， with prescriptions as Maziren Pills （麻子仁丸）， Qinlian Pingwei Powder （芩连平胃散）， and Jiawei Lianli Decoction （加味连理汤） accordingly.

OBJECTIVE To study the relationship between frequency specific free-field tone burst cortical auditory evoked potentials(CAEP)and aided behavioral audiometry to provide rapid,reliable insights for predicting hearing intervention efficiency in hard to cooperate cochlear implant patients.METHODS The study comprised of 22 cochlear implant pediatric patients(22 ears)free-field tone burst CAEP P1 response thresholds,free-field behavioral thresholds determined within the group across frequencies 0.5,1,2 and 4 kHz were collected for correlation analysis.RESULTS The free-field tone burst CAEP P1 response thresholds and free-field behavioral audiometric thresholds in cochlear implant pediatric patients for testing frequencies 0.5,1,2,4 kHz were compared and r correlation coefficients found were 0.567,0.670,0.637 and 0.762 across the frequencies respectively(P<0.01).The mean difference between free-field CAEP P1 response threshold and free-field behavioral thresholds for cochlear implant patients differ by 5-8 dB with statistical significance.CONCLUSION Free-field tone burst CAEP can be used for cochlear implant programming validation in patients that fail to cooperate in behavioral testing,thus is applicable in cochlear implant programming clinical practice.

Objective To understand the incidence and characteristics of adverse drug reactions(ADRs)of carbapenems,explore the relevant risk signals,and provide a reference for clinically safe drug use.Methods All spontaneous reports of carbapenem drug-related ADRs from January 2008 to October 2022 in the Adverse Drug Reaction Monitoring Center,PLA General Hospital's ADR database were retrieved,and information such as patients'general conditions,involved systems and organs damage,and the names of ADRs involved were retrospectively analysed.Using the reporting odd ratio method,the proportional reporting ratio method,the Medicines and Healthcare Products Regulatory Agency method,and information component method to obtain risk signals of carbapenem antimicrobial drug-related ADR.Results A total of 2 642 ADR reports of carbapenems were reported,of which 410 serious ADR reports(15.52％)were serious ADR reports,five cabapenem antimirobial drug species were mainly involved.In descending order of composition were imipenem cilastatin(51.28％),meropenem(32.13％),biapenem(8.10％),ertapenem(7.68％),and panipenem(0.79％).The male to female ratio of patients was 1.74:1,with the most age＞60 years(59.69％).A total of 14"drug-ADR name"combinations generated risk signals in all four data mining methods,with meropenem being the most signals,and imipenem cilastatin and ertapenem had a high number of reported ADR in nervous system.Conclusion The results of risk signal mining are basically consistent with the known carbapenem ADR information,during the use of carbapenem antimicrobial drugs in the clinic,it is recommended to monitor patients'liver and kidney functions as well as blood biochemical indexes,so as to strengthen the awareness of vigilance in the clinical use of carbapenem antimicrobial drugs,and timely recognize and deal with ADRs in a timely manner,and to avoid the occurrence of serious ADRs.

Objective To investigate the correlation between muscle mass and gait parameters in patients with cerebral small vessel disease(CSVD),as well as the impact of reduced muscle mass on the occurrence of falls in CSVD patients.Methods This study was employed a cross-sectional design.Ninety-five inpatients with CSVD confirmed by the Department of Neurology of the Seventh Medical Center of Chinese People's Liberation Army General Hospital from January 1,2022 to June 1,2023 were included consecutively.The 95 patients with CSVD were divided into two groups,namely the reduced muscle mass group and the normal muscle mass group,based on the criteria of appendicular skeletal muscle mass(ASM)≤7.0 kg/m2 for males and ASM ≤5.7 kg/m2 for females as reduced muscle mass.Baseline data(sex,age,years of schooling,number of accompanying diseases[hypertension,hyperlipidemia,diabetes,angina pectoris,myocardial infarction,and migraines]),cognitive function assessment results(mini-mental status examination[MMSE],verbal fluency test[VFT],clock drawing test[CDT],and trail-making test part-B[TMT-B]),gait characteristics(basic gait parameters[gait speed,stride time,stride length,stride frequency]and reanalysis gait parameters[variation coefficient of gait speed,stride time,stride length,stride frequency,and time-phase coordination index,gait asymmetry index]),CSVD imaging findings(cerebral microbleeds,lacunar infarcts,and white matter hyperintensities),and history of falls.The differences in baseline data,cognitive function assessment results,and gait characteristics between the reduced muscle mass group and the normal muscle mass group were compared and analyzed.Linear regression was used to analyze the correlation between muscle mass and gait parameters.The 95 CSVD patients were divided into fall group and non-fall group,and the differences in baseline data,cognitive function assessment results,gait characteristics,CSVD imaging findings,and muscle mass between the two groups were compared.Binary Logistic regression analysis was used to evaluate the impact of reduced muscle mass on falls.Results(1)The majority of patients in the reduced muscle mass group were females(67.7％[21/31]).There was a statistically significant difference in the sex distribution between the reduced muscle mass group and the normal muscle mass group(x2=6.143,P=0.013).There were no statistically significant differences in the other baseline characteristics and cognitive function between the two groups(all P＞0.05).(2)Compared to the normal muscle mass group,patients in the reduced muscle mass group had slower gait speed([0.72±0.16]m/s vs.[0.94±0.15]m/s),longer stride time([1.22±0.12]s vs.[1.08±0.08]s),shorter stride length([0.84±0.19]m vs.[1.00±0.14]m),and lower step frequency([100±9]steps/min vs.[112±8]steps/min).The coefficients of variation for gait speed(11.579[8.163,15.870]％vs.7.304[5.873,9.959]％),stride time(3.876[2.778,5.769]％vs.2.480[1.874,3.001]％),stride length(7.800[5.400,10.700]％vs.5.600[4.100,7.950]％),step frequency(5.313[3.568,7.272]％vs.3.674[3.099,5.082]％),and time-phase coordination index(5.894[4.392,9.080]％vs.3.828[3.031,5.972]％)were all increased,and the differences were statistically significant(all P＜0.05).There was no statistically significant difference in gait asymmetry index between the two groups(P＞0.05).Further analysis with sex and lacunar infarction as potential confounding factors showed that there were statistically significant differences in baseline gait parameters between the normal muscle mass group and the reduced muscle mass group(all P＜0.01).In the reanalysis of gait parameters,only the differences in the coefficients of variation for gait speed and stride time were statistically significant(both P＜0.05).(3)When analyzing ASM as a continuous variable,age and CDT as potential confounders,and stratifying by sex,the results showed that in male patients,baseline gait parameters(gait speed,stride time,stride length,and step frequency with 95％CI ranging from 0.057 to 0.152,-0.105 to-0.023,0.013 to 0.097,and 1.686 to 8.854,respectively),as well as coefficients of variation for stride time(95％CI-0.016 to-0.003)and stride length(95％CI-0.026 to-0.006),were correlated with muscle mass reduction(all P＜0.05).In female patients,gait speed(95％CI0.034 to 0.166)and coefficient of variation for gait speed(95％CI-0.059 to-0.010),stride time(95％CI-0.110 to-0.011),coefficient of variation for stride time(95％CI-0.025 to-0.001),and stride length(95％CI 0.018 to 0.163)were correlated with muscle mass reduction(all P＜0.05).(4)Muscle mass reduction was an independent risk factor for falls(OR,5.044,95％CI 1.840 to 13.827,P=0.002).Conclusions The preliminary analysis of this study suggests that there is a certain correlation between muscle mass and gait parameters in patients with CSVD.Additionally,the study indicates that a decrease in muscle mass among CSVD patients may increase the risk of falls.Therefore,it is important to prioritize the management of muscle mass in CSVD patients.

Objective:To compare the gait characteristics of cognitive and motor dual task walking (DTW) in patients with cerebral small vessel disease (CSVD), and determine the best gait parameters to diagnose CSVD and judge the severity of the disease.Methods:A total of 106 patients with CSVD and 21 healthy individuals were included from September 1, 2020 to July 1, 2021 in the Seventh Medical Center of Chinese People′s Liberation Army General Hospital. According to the Fazekas scores, the subjects were divided into mild ( n=34, 1 point), moderate ( n=34, 2 points), severe ( n=38,3 points) groups and control group ( n=21). Participants were recorded parameters under single task walking (STW) and DTW conditions, and calculated dual task effect (DTC) through the difference between single task and dual task. The differences in gait variances and their DTC were shown by generalized estimation equations when performed in STW and DTW and 4 groups of the severity of disease. Post-hoc comparisons were corrected using Bonferroni′s method. Spearman analyses were applied to explore the correlations between gait parameters and their DTC during STW or DTW and severity of disease. Based on the Logistic model, combining predictors or probabilities were gained and applied to establish receiver operating characteristic curve in order to calculate sensitivity, specificity, and the area under the curve. Results:In the control group, there was no statistically significant difference in gait parameters between STW and DTW. In the CSVD group, the gait parameters of STW were significantly better than cognitive or motor DTW (all P<0.05). In the control group, there was no statistically significant difference in basic gait parameters under different tasks (all P>0.05). In cognitive DTW, temporal gait parameters (stride frequency and stride time) deteriorated significantly only in moderate and severe groups [stride frequency:moderate group 100.220±1.795/min,severe group 94.525±2.139/min;stride time:moderate group (1.227±0.024) s, severe group (1.299±0.031) s], but spatial parameters [stride length: control group (1.050±0.021) m, mild group (0.974±0.022) m, moderate group (0.903±0.025) m, severe group (0.793±0.026) m; stride speed: control group (0.944±0.028) m/s, mild group (0.866±0.030) m/s, moderate group (0.751±0.027) m/s, severe group (0.606±0.022) m/s] were significantly different among all groups (except the control group and mild group;all P<0.05). The DTC of all gait parameters during cognitive DTW was higher than that during motor DTW (all P<0.05) for CSVD patients. While no any difference was found between cognitive DTW and motor DTW in the control group (all P>0.05). Similarly, the temporal parameters′ DTC of cognitive DTW was abnormal only in the late stage of disease, while the spatial parameters′ DTC showed statistically significant difference among all the groups (including the control group and the mild group;all P<0.05). Correlation coefficients of the spatial parameters and their DTC in condition of cognitive DTW were significantly higher than temporal parameters and their DTC (0.50< r<0.64 vs 0.15< r<0.39). The area under curve of the combined predictor was significantly higher than that of any single index. Conclusions:Cognitive DTW can better reflect the abnormal gait of CSVD patients. The spatial parameters and DTC of cognitive DTW could effectively diagnose CSVD and distinguish the disease of severity. And DTC might be better indicators. For diagnosis of CSVD, there was no significant discrepancy between the spatial parameters and DTC, but the combined predictor could significantly improve the sensitivity and reduce the false negative rate.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Objective:To explore the effect of colonoscopy combined with X-ray stent implantation in the treatment of colorectal cancer intestinal obstruction, and analyze the risk factors of postoperative delayed bleeding.Methods:From November 2016 to December 2020, 382 patients with colorectal cancer intestinal obstruction in Hainan Provincial People′s Hospital were selected. Among them, 254 patients were treated by colonoscopy combined with X-ray stent implantation (stent implantation group), and 128 patients were treated by emergency radical resection (control group). The operation time, intraoperative bleeding, number of lymph node dissections, tumor diameter, incision length, exhaust time, hospital stay, fluid feeding time, fistulation, perioperative death and delayed bleeding were compared between 2 groups. Based on the random number generated by the computer, 254 patients who underwent colonoscopy combined with X-ray stent implantation were divided into training set (190 cases) and test set (64 cases) according to the ratio of 3∶1. In the training set, the patients were divided into postoperative delayed bleeding and non postoperative delayed bleeding, and the clinical indicators were compared; the multivariate Logistic regression model was performed to analyze the independent risk factors of postoperative delayed bleeding, and the prediction model of postoperative delayed bleeding was established and verified according to the independent risk factors.Results:All patients in the stent implantation group were successfully implanted with stents, and the obstructive symptoms were relieved 24 to 48 h after operation. The operation time, intraoperative bleeding, incision length, fistulation rate, exhaust time, hospital stay and fluid feeding time in stent implantation group were significantly lower than those in control group: (88.89 ± 5.97) min vs. (116.58 ± 20.17) min, (33.18 ± 16.52) ml vs. (92.35 ± 25.64) ml, (4.50 ± 0.96) cm vs. (14.26 ± 2.88) cm, 10.24% (26/254) vs. 98.44% (126/128), (1.18 ± 0.58) d vs. (1.53 ± 0.77) d, (7.69 ± 5.12) d vs. (12.88 ± 6.54) d and (1.46 ± 0.68) d vs. (2.12 ± 1.18) d, the number of lymph node dissections was significantly higher than that in control group: (19.88 ± 4.47) lymph nodes vs. (17.47 ± 3.11) lymph nodes, and there were statistical differences ( P<0.01); there were no statistical differences in tumor diameter and perioperative fatality rate between 2 groups ( P>0.05). Among 190 patients in the training set, 18 patients had postoperative delayed bleeding, with an incidence of 9.47%; 172 cases did not have postoperative delayed bleeding. The age, course of obstruction, complete obstruction rate, intestinal almost occlusion rate under enteroscopy, intraoperative bleeding rate and preoperative intestinal surgery history rate in patients with postoperative delayed bleeding were significantly higher than patients without postoperative delayed bleeding: (69.52 ± 10.54) years old vs. (58.65 ± 15.87) years old, (14.56 ± 10.12) d vs. (8.13 ± 7.68) d, 11/18 vs. 20.35% (35/172), 11/18 vs. 16.28% (28/172), 7/18 vs. 11.63% (20/172) and 12/18 vs. 37.79% (65/172), and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistics regression analysis result showed that old age, long duration of obstruction, complete obstruction, almost intestinal obstruction under enteroscopy and intraoperative bleeding were independent risk factors for postoperative delayed bleeding in patients with colorectal cancer intestinal obstruction undergoing colonoscopy combined with X-ray stent implantation ( OR = 3.925, 4.802, 1.727, 2.710 and 2.581; 95% CI 1.352 to 8.330, 1.064 to 8.869, 1.063 to 2.804, 1.118 to 4.400 and 1.689 to 3.479; P<0.05 or<0.01), while the history of preoperative intestinal surgery was not related to postoperative delayed bleeding ( P>0.05). The consistency indexes of nomogram training set and test set were 0.742 and 0.726 (95% CI 0.684 to 0.845 and 0.640 to 0.812). The receiver operating characteristic (ROC) curve analysis results of 2 models showed that the area under the curve (AUC) of the training set nomogram model and Tree Augmented Na?ve Bayes (TAN) model was 0.758 and 0.752 respectively, and the AUC of the test set nomogram model and TAN model was 0.702 and 0.706 respectively. The prediction accuracy of training set nomogram model and TAN model was 84.74%(161/190) and 85.26%(162/190) respectively, the prediction accuracy of test set nomogram model and TAN model was 82.81%(53/64) and 84.38%(54/64) respectively. Conclusions:Colonoscopy combined with X-ray stent implantation is safe and feasible in patients with colorectal cancer intestinal obstruction. But for the old age, long duration of obstruction, complete obstruction, almost intestinal obstruction under colonoscopy and intraoperative bleeding, careful operation should be carried out to reduce the occurrence of postoperative delayed bleeding.

Hepatoma is one of the most common malignant tumors of digestive system worldwide， and a main factor leading to cancer-related deaths. Its incidence is increasing year by year， posing a serious threat to human health. Currently， hepatoma is mainly treated by surgical resection， liver transplantation， radiation and drugs， but there are certain adverse reactions and problems of high recurrence rate and low survival rate. Chinese medicine has unique advantages in improving the comprehensive curative effect of hepatoma and reducing adverse reactions. With a variety of active ingredients， Chinese medicine can induce hepatoma cell apoptosis， inhibit the proliferation， migration and reverse multidrug resistance through multiple targets， thus exerting anti-hepatoma effect. It has become an important means for the prevention and treatment of hepatoma as well as a rich resource for anti-hepatoma drug research and development. Wnt/β-catenin signaling pathway， one of the most classical pathways in cancer， is involved in tumor cell proliferation， cell cycle， migration， invasion and tumor angiogenesis. Recently， many studies have reported that the active ingredients of Chinese medicine can play an anti-hepatoma role through this pathway. Therefore， this paper summarized the domestic and foreign literature in recent years， analyzed the relationship between wnt/β-catenin signaling pathway and the specific mechanism of hepatoma occurrence and development， and combed the literature on the effect of flavonoids， terpenoids， alkaloids， polysaccharides and other active ingredients of Chinese medicine on inducing hepatoma cell apoptosis， regulating cell cycle and inhibiting the invasion and metastasis through Wnt/β-catenin signaling pathway. In addition， the paper summarized the research progress of relevant active ingredients of Chinese medicine against hepatoma， to explore their specific mechanism against hepatoma through Wnt/β-catenin signaling pathway， so as to provide theoretical reference for further development of anti-hepatoma drugs.

Chemically defined medium is widely used for culturing mouse embryonic stem cells (mESCs), in which N2B27 works as a substitution for serum, and GSK3β and MEK inhibitors (2i) help to promote ground-state pluripotency. However, recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs. Here, we demonstrated the deficient bone morphogenetic protein (BMP) signal in the chemically defined condition is one of the main causes for the impaired pluripotency. Mechanistically, activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream targets Ube2s and Chmp4b. More importantly, BMP4 promotes a distinct in vivo developmental potential and a long-term pluripotency preservation. Besides, the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression. Taken together, our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.
Animals ; Bone Morphogenetic Protein 4/metabolism* ; Cell Differentiation ; Chromosomal Instability ; Endosomal Sorting Complexes Required for Transport ; Mice ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Mouse Embryonic Stem Cells/cytology* ; Pluripotent Stem Cells/cytology* ; Signal Transduction ; Ubiquitin-Conjugating Enzymes

ObjectiveTo explore the effective components， targets， and mechanism of Houttuynia cordata against lung cancer by means of systems pharmacology and further to provide a reference for the further development and clinical application of this medicinal. MethodChemical components of H. cordata were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the active components were screened based on oral bioavailability （OB） and drug-likeness （DL）. Then the potential targets were predicted， followed by enrichment analysis. Finally， sodium houttuyfonate （SH） was selected for verifying the anti-tumor mechanism. Cell counting kit-8 （CCK-8） assay was used to evaluate the effect of SH on the in vitro proliferation of two lung cancer cell lines： A549 and LLC， and the regulation of tumor-related proteins by SH was verified by Western blot. ResultA total of 7 active compounds and 352 targets of the active components were screened out. According to the enrichment analysis of targets， H. cordata had potential therapeutic effects on cancer. SH had inhibitory effect on both A549 and LLC. Western blot results showed that G₁/S-specific Cyclin D₁， E₁ and cyclin-dependent kinase （CDK）2， CDK4 all tended to be down-regulated， and Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） also changed significantly. ConclusionH. cordata has the potential anti-tumor effects by arresting the tumor cells in the G₁ phase through the JAK2/STAT3 pathway.