Erchentang is a classic formula widely used by medical practitioners throughout history. In this paper，ancient and modern literature of Erchentang were collected， and bibliometrics was employed to analyze its historic evolution，prescription meaning，herbs origin， processing method，preparation methods， and clinical application. A total of 84 pieces of data were collected， and 58 pieces of data involving 53 ancient medical Chinese books were screened， sorted， and processed. Combined with research of modern scholars，the research has found that the Erchentang originated from the Taiping Huimin Huiye Shijie Fang compiled by the Imperial Medical Bureau of the Song Dynasty. The basic information about the origin of the drugs is quite clear. Pinelliae rhizoma in the formula is the dried tuber of Pinellia ternata. Citri exocarpium rubrum is the dried mature peel of Citrus reticulata and its cultivated varieties， with the inner white membrane removed. Poria is the whitest dry sclerotia of Poria cocos； Glycyrrhizae radix et rhizoma is the dried root and rhizome of the Glycyrrhiza uralensis. The dosage is 5.70 g Pinelliae rhizome and Citri exocarpium rubrum， 3.43 g Poria， and 1.69 g Glycyrrhizae radix et rhizoma praeparata cum melle. During the decoction process， the above-mentioned herbs should be chopped， with 300 mL water， 7 g ginger in thick slices， and 2 g Mume fructus added， and it was then simmered together to 180 mL. After removing the medicinal residue， it can be taken warmly. Erchentang has the effect of drying dampness and resolving phlegm， regulating Qi and harmonizing the middle. It can be used in treating the syndrome of phlegm and dampness，as well as symptoms such as frequent cough，white phlegm，fullness in chest and diaphragm，nausea and vomiting，limb drowsiness，anorexia，dizziness，palpitations，white and greasy tongue coating， and slippery pulse. The above results provide reference for future research and development of Erchentang.

ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

BACKGROUND:Osteoarthritis is now considered a metabolic disease.Previous studies have shown that glycolysis plays an important role in the occurrence and development of osteoarthritis.Compound 3k,as a novel small molecule inhibitor of glycolysis,has anti-inflammatory and anti-tumor effects.Therefore,it can target glycolysis and is expected to provide new ideas for the treatment of osteoarthritis. OBJECTIVE:To explore the role of Compound 3k in osteoarthritis caused by glycolytic overactivity based on the hypoxia-inducible factor 1 alpha(HIF-1α)/reactive oxygen species(ROS)pathway. METHODS:ATDC5 chondroblasts at logarithmic growth phase were taken to induce osteoarthritis in an in vitro cellular model by the action of 10 ng/mL interleukin-1β for 24 hours.The cytotoxicity of Compound 3k at different concentrations(0.25,0.5,1,2.5,5,10,15 μmol/L)was detected by cell counting kit-8 assay,and the appropriate concentrations were selected for the subsequent experiments.The chondrocytes were randomly divided into control,model and treatment groups.The model group was induced with 10 ng/mL interleukin 1β,and the treatment group was pre-stimulated with Compound 3k for 2 hours and then co-cultured with interleukin 1β.The proliferation of the cells in each group was detected by the cell counting kit-8 assay;the inflammatory level of the cells in each group was detected by the ELISA kit;the ROS,extracellular lactate and glucose contents were detected using the kit;qRT-PCR and western blot were used to detect the levels of related inflammatory factors,interleukin-6 and tumor necrosis factor-α,glycolysis-related genes glucose transporter protein-1,glyceraldehyde 3-phosphate dehydrogenase,monocarboxylate transporter protein-1 and HIF-1α. RESULTS AND CONCLUSION:Compared with the control group,the model group showed a decrease in cell proliferative activity,active glycolysis level,manifested by an increase in extracellular lactate content(P<0.001)and a decrease in glucose content(P<0.001),interleukin-6(P<0.000 1)and tumor necrosis factor-α(P<0.001).The expression levels of glycolysis-related genes glucose transporter protein-1(P<0.001),glyceraldehyde 3-phosphate dehydrogenase(P<0.001),monocarboxylic acid transporter protein-1(P<0.001)and HIF-1α(P<0.001)in the model group were all up-regulated,accompanied by oxidative stress and overproduction of ROS.Compared with the model group,Compound 3k treatment effectively increased cell proliferation activity and inhibited the level of overactive glycolysis(P<0.001),while suppressing the expression of genes related to inflammation(P<0.001)and glycolysis in osteoarthritic chondrocytes,inhibiting oxidative stress,downregulating the expression level of HIF-1α(P<0.000 1)and decreasing the content of ROS.To conclude,Compound 3k inhibits interleukin-1β induced chondrocyte inflammation,and its mechanism may be related to glycolysis and HIF-1α/ROS mediated oxidative stress.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To evaluate the cross-neutralization effect of multivalent recombinant receptor-binding domain(RBD)dimer protein vaccine against SARS-CoV-2 variant strains, so as to provide an experimental basis for the development ofbroad-spectrum SARS-CoV-2 vaccines. Methods Twenty-two female SD rats were randomly divided into ZF2202(B) group(8 rats immunized with quadrivalent recombinant RBD dimer protein vaccine), ZF2202(A) group(6 rats immunized withbivalent recombinant RBD dimer protein vaccine) and normal saline control group(8 rats). The rats were immunized intra-muscularlyat0,21and42days,respectively,withadoseof0.25mL/rat.Fourteendaysafterthelastimmunization,theneutralizingantibodies against Delta, BA.4/5, BQ.1.1, XBB.1, EG.5 and BA.2.86 in serum of rats in ZF2202(B) and ZF2202(A) groupswere detected by pseudovirus neutralization assay, and the secretion of IFNγ and IL-4 in spleen lymphocytes of rats in ZF2202(B)and normal saline control groups were analyzed by ELISpot. Results The levels of neutralizing antibodies againstpseudovi-ruses BA.4/5, BQ.1.1, XBB.1, EG.5 and BA.2.86 in serum of rats in ZF2202(B) group were significantly higher than those inZF2202(A) group(U = 3, 1, 1, 1, 0, P = 0. 004 7, 0. 001 3, 0. 001 3, 0. 001 3, and 0. 000 7, respectively). Compared withnormal saline group, the number of specific spots of IFNγ secreted by spleen lymphocytes in ZF2202(B) group increased signifi-cantly(U = 4, P = 0. 001 4), and the number of IL-4 specific spots also increased significantly(t = 3. 775, P = 0. 002 1).Conclusion Both ZF2202(A) and ZF2202(B) provide cross-protective immunity against SARS-CoV-2 variants, whileZF2202(B)exhibitsbetterprotectiveeffectthanZF2202(A)ontheepidemicstrains,andexhibitsabroaderspectrumofefficacy.

Objective To investigate the impact of sleep modes on the risk for diseases of the body systems.Methods Based on a subset of UK Biobank dataset comprising 87 617 participants,3 sleep dimensions including 6 sleep indicators were obtained through a wrist-worn accelerometer,that is sleep duration and onset,sleep rhythm(relative amplitude and stability),and sleep quality(sleep efficiency and number of awakenings).Latent profile analysis(LPA)was applied to identify and classify distinct sleep modes.Then their longitudinal medical records were the association between different sleep modes and the risk for 467 diseases.Results LPA identified 5 subgroups of unique sleep modes in the participants.Among the 5 subgroups,the subgroup 4 had relatively optimal levels in above sleep indicators.Compared to the subgroup 4,the other 4 subgroups exhibited variations in different sleep dimensions,with at least one indicator demonstrating an unfavorable trend.These subgroups also revealed differences in racial composition,shift work and social deprivation index.Moreover,there were notable differences in the risk of various system diseases among the subgroups(P<0.05).When compared to the subgroup 4,the other 4 subgroups exhibited an elevated risk for certain diseases(comprising a total of 126 diseases),with the diseases of the circulatory system,digestive system and musculoskeletal system most common.Among the 5 subgroups,the subgroup 2(shorter sleep duration and later sleep onset)and the subgroup 5(rhythm disorder)had the highest counts of associated risks,amounting to 85 and 91 types,respectively,but there was certain difference in their systematic composition.Conclusion There are different sleep modes within the participants,and the modes are potentially associated with an increased risk for diseases of body systems.Comprehensive interventions targeting overall sleep modes rather than single sleep indicator may yield obvious health benefits.

Objective To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

Objective To investigate the transgenerational effects of paternal PM2.5 exposure on offspring growth and development,and to preliminarily elucidate the role of sperm DNA methylation modifications in mediating these effects.Methods Eight-week-old male C57BL/6 mice were randomly divided into filtered air(FA),unfiltered air(UA),and concentrated PM2.5(CAP)groups,with 10 animals in each group.The exposure was conducted from November 2019 to April 2020,and then,these male mice were mated with unexposed females to generate F1 offspring,which were bred successively to produce F2 and F3 generations.All the offspring were living in PM2.5-free environment.The birth body weight,birth number,and sex ratio of the offspring were recorded,body weight growth was monitored,and organ coefficients of the heart,liver,lung,and brain were calculated.Whole-genome methylation sequencing was performed on the sperm DNA of the CAP group,FA group,and their F1 generation offspring to screen for differentially methylated regions,and the genes and pathways associated with these regions were analyzed.Results When compared with the F1～F3 offspring of the FA group,the CAP group had significantly reduced birth body weight in the F1 generation(P<0.05),no statistical differences were observed in the birth body weight in the F2 and F3 generations(P>0.05),or either in the sex ratio and birth number among the F1,F2 and F3 generations.Compared with the FA group offspring,the F1～F3 offspring of CAP group exhibited delayed body weight gain,especially in the males(P<0.05),the CAP-F1 male generation had obviously elevated liver organ coefficient(P<0.01),but no statistical changes were observed in the heart,lung,or brain coefficients among the F1～F3 generations.Between the FA group and the CAP group,37 997 differentially methylated regions were detected,with a reduction of approximately 50%in the number of differentially methylated regions in the F1 generation.Differentially methylated genes in F0 and F1 sperm were potentially related to developmental processes,including imprinting genes(Gnas,Igf2)and metabolic genes(Ppard,Rps6kb1).Conclusion Paternal exposure to PM2.5 leads to reduced birth weight and intergenerational growth retardation in offspring.Its impact on phenotypic effects is gradually weakened during intergenerational transmission.Changes in the methylation of development-related genes in sperm may be one of the mechanisms mediating this intergenerational effect.

Adenosine triphosphate(ATP),as the core energy metabolism molecule in living systems,has dynamic changes closely related to fundamental physiological processes.To meet the urgent demand for spatiotemporal ATP detection in vivo and in situ,the development of highly sensitive multifunctional synchronous sensing fluorescent probes has become a recent research focus.These dual-function probes achieve fluorescence detection of dual targets by designing recognition sites for ATP alongside biological factors or microenvironment parameters such as reactive oxygen/nitrogen/sulfur species,metal ions,and enzymes,enabling physiological/pathological state correlation analysis through bioimaging.This paper systematically reviews recent advances in fluorescent probes for the collaborative detection of ATP and key biomolecules.It specifically examines probe construction strategies based on specific molecular recognition mechanisms(e.g.,metal coordination competition,electrostatic interactions,and host-guest recognition),multi-modal optical signal transduction mechanisms(ratiometric fluorescence,fluorescence lifetime,and photodynamic therapy),and their applications in pathological models such as oxidative stress monitoring,metal homeostasis imbalance,and enzyme activity co-detection.Finally,from the perspective of molecular probe engineering,current challenges and future research directions are proposed to provide methodological support for precise analysis of ATP-related life process regulation networks.

Objective To investigate the predictive value of serum interleukin-17(IL-17)combined with eotaxin-3 for poor prognosis in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods A total of 213 patients with AECOPD admitted to Beijing Municipal Armed Police Force Hospital from May 2018 to July 2023 were selected as the disease group.According to the prognosis of patients,they were divided into good prognosis group(133 cases)and poor prognosis group(80 cases).At the same time,205 physical examination healthy people in Beijing Municipal Armed Police Force Hospital were selected as the healthy group.The serum levels of IL-17 and eotaxin-3 were detected by enzyme-linked immu-nosorbent assay.The clinical data of poor prognosis group and good prognosis group were compared.Pearson correlation analysis was used to analyze the correlation between serum IL-17 level and eotaxin-3 in AECOPD patients.Multivariate Logistic regression analysis was used to analyze the related factors affecting the progno-sis of AECOPD patients.The receiver operating characteristic(ROC)curve was used to evaluate the predic-tive value of serum IL-17 and eotaxin-3 levels for the prognosis of AECOPD patients.Results Compared with the healthy group,the serum levels of IL-17 and eotaxin-3 were increased in the disease group(P<0.05).Compared with the good prognosis group,the poor prognosis group had significant increases in serum IL-17 and eotaxin-3 levels(P<0.05).Serum IL-17 level was positively correlated with eotaxin-3 in AECOPD pa-tients(r=0.537,P<0.001).There were significant differences in Global Initiative for Chronic Obstructive Lung Disease(GOLD)grade,blood oxygen partial pressure(PaO2)and carbon dioxide partial pressure(PaCO2)between the poor prognosis group and the good prognosis group(P<0.05).GOLD grade,PaCO2,serum IL-17 and eotaxin-3 levels were risk factors for poor prognosis in patients with AECOPD(P<0.05),and PaO2 was a protective factor for poor prognosis in patients with AECOPD(P<0.05).The area under the curve of serum IL-17 and eotaxin-3 combined to predict the prognosis of AECOPD patients was 0.885,the sensitivity was 80.00%,and the specificity was 83.46%,which was better than that of IL-17 and eotaxin-3 a-lone(Zcombiation-IL-17=4.045,P<0.001,Zcombiation-eotaxin-3=3.254,P=0.001).Conclusion The serum levels of IL-17 and eotaxin-3 are increased in AECOPD patients.The combination of IL-17 and eotaxin-3 has predictive value for the prognosis of AECOPD patients.