ObjectiveTo clarify the graded quantitative diagnostic characteristics of lung qi deficiency syndrome in chronic obstructive pulmonary disease （COPD） based on latent class analysis combined with a hidden structure model. MethodsClinical data， including the four diagnostic methods of traditional Chinese medicine （TCM）， were collected from 745 COPD patients with lung qi deficiency syndrome. Latent class modeling was performed using R 4.1.2 software， and each patient was classified into one of three severity categories （mild， moderate， or severe） based on probabilistic parameterization， parameter estimation， and model fitting. A database was established for different severity levels of lung qi deficiency syndrome. Based on this， Lantern 5.0 software was used to construct hidden structure models for mild， moderate， and severe lung qi deficiency syndrome， and syndrome differentiation rules were developed through comprehensive clustering. ResultsA latent class model was constructed using 28 symptoms and signs with a frequency greater than 10%. Considering TCM theory and model simplicity， the optimal model was determined when the number of latent classes was three， categorizing lung qi deficiency syndrome into mild （298 cases）， moderate （164 cases）， and severe （283 cases）. Hidden structure models were separately developed for each severity level， and syndrome differentiation rules were established. A comparison of common symptoms in the syndrome differentiation rules for mild and moderate lung qi deficiency syndrome showed no statistically significant differences in diagnostic values and weights （P＞0.05）， leading to their combined analysis and the development of a unified syndrome differentiation rule. Value and weight of quantitative diagnosis of mild-to-moderate lung qi deficiency syndrome were as followed： shortness of breath （diagnostic value 9.3， diagnostic weight 86.92%）， dyspnea on exertion （8.2， 76.64%）， low voice and reluctance to speak （6.7， 62.62%）， poor appetite （4.0， 37.38%）， loose stools （4.0， 37.38%）， weak cough sound （2.9， 27.10%）， wheezing （2.3， 21.50%）， fatigue （1.8， 16.82%）， spontaneous sweating （1.7， 15.89%）， susceptibility to colds （1.6， 14.95%）， swollen tongue （1.4， 13.08%）， teeth marks on the tongue edge （1.2， 11.21%）， deep pulse （1.6， 14.95%）， with a diagnostic threshold of 10.3. Value and weight of quantitative diagnosis of severe lung qi deficiency syndrome were as followed： weak cough sound （15.1， 61.13%）， soreness and weakness of the waist and knees （12.6， 51.01%）， shortness of breath （11.1， 44.94%）， low voice and reluctance to speak （8.3， 33.60%）， frequent nocturia （6.1， 24.70%）， spontaneous sweating （3.7， 14.98%）， susceptibility to colds （3.5， 14.17%）， teeth marks on the tongue edge （7.8， 31.58%）， pale tongue body （1.9， 7.69%）， white tongue coating （5.5， 22.27%）， thin pulse （1.5， 6.07%）， with a diagnostic threshold of 23.7. ConclusionThe combination of latent class analysis and a hideen structure model effectively clarified the graded quantitative diagnostic characteristics of lung qi deficiency syndrome， providing a reference for the quantitative diagnosis of other fundamental syndromes in TCM.

OBJECTIVE To investigate the efficacy and safety of tirofiban for early neurological deterioration in patients with acute ischemic stroke. METHODS A total of 126 patients with early neurological deterioration of acute ischemic stroke who were admitted to the Department of Neurology， Heji Hospital Affiliated to Changzhi Medical College from January 2022 to December 2023 were selected and divided into observation group and control group according to random number table method， with 63 cases in each group. All patients received standardized treatment such as lipid-lowering and blood pressure-lowering therapy. Based on the standard treatment， patients in the control group additionally took Aspirin enteric-coated tablets 100 mg+Clopidogrel bisulfate tablets 75 mg orally （once a day， for 14 consecutive days）. The patients in the observation group received Tirofiban hydrochloride and sodium chloride injection based on the standardized treatment [first intravenous infusion of 0.40 μg/（kg·min） for 30 min， and then continuous intravenous infusion of 0.10 μg/（kg·min） for 47.5 h]； subsequently， patients were given Aspirin enteric-coated tablets （100 mg） and Clopidogrel bisulfate tablets （75 mg） once a day for 14 consecutive days. The clinical efficacy， the National Institutes of Health Stroke Scale （NIHSS） score， modified Rankin Scale （mRS） score， and hemorheological indexes before and after treatment were compared between the two groups， and the adverse reactions were recorded. RESULTS The total effective rate （87.30%） of the observation group was significantly higher than that of the control group （71.43%） （P＜0.05）. NIHSS scores of the two groups at 1st， 7th and 14th day after treatment， the mRS score at 90th day after treatment， and the platelet aggregation rate， whole blood viscosity， plasma viscosity and fibrinogen at 14th day after treatment were significantly lower than those before treatment in the same group， and the observation group was significantly lower than the control group at the same period （P＜0.05）. The total incidences of adverse reactions such as nausea， headache， fever， gastrointestinal bleeding， oral and nasal mucosal bleeding and thrombocytopenia in both groups of patients were 28.57% respectively， with no statistically significant difference （P＞0.05）. CONCLUSIONS For patients with early neurological deterioration in acute ischemic stroke， the addition of tirofiban can accelerate the recovery of neurological function， improve blood hyperviscosity and platelet aggregation， and improve the prognosis of patients with good safety.

Gastrointestinal tumors （GTs）， including colorectal cancer， gastric cancer， liver cancer， pancreatic cancer， and esophageal cancer， are increasing in incidence worldwide and have become one of the major diseases threatening human health. Tumor stem cells （TSCs）， an undifferentiated subpopulation within tumor tissues， possess biological characteristics such as self-renewal， multidirectional differentiation， high tumorigenicity， and resistance to radiochemotherapy. They play an important role in the occurrence， progression， recurrence， and metastasis of GTs and have increasingly become a research hotspot in GT treatment. Although modern medicine has made remarkable progress， there remain many problems in therapeutic approaches targeting TSCs. In this context， traditional Chinese medicine （TCM）， with its favorable safety profile and multi-target mechanisms， has shown potential advantages and value in regulating TSCs. It can reduce TSC drug resistance， enhance the sensitivity of tumor cells to chemotherapeutic agents， inhibit tumor growth and metastasis， and has shown unique advantages in improving the quality of life and prolonging the survival of GT patients. Studies have found that active components of Chinese medicine， such as terpenoids， polyphenols， flavonoids， glycosides， and quinones， and Chinese medicine compound formulas， including Zuojin pills， Sijunzi decoction， Biejiajian pills， and Xuanfu Daizhe decoction， can inhibit TSCs-related signaling pathways such as the Notch signaling pathway， the Wnt/β-catenin signaling pathway， the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， and the Hippo signaling pathway. They also reduce the expression of TSC surface markers， including sex-determining region Y-box 2 （SOX2）， sex-determining region Y-box 9 （SOX9）， octamer-binding transcription factor 4 （OCT4）， prominin-1 （CD133）， cluster of differentiation 44 （CD44）， cluster of differentiation 24 （CD24）， and thyroid transmembrane protein 1 （CD90）， thereby hindering TSC differentiation， accelerating their metabolic processes， improving the tumor microenvironment， and consequently inhibiting GT growth. This study collects and analyzes recent research on the regulation of TSCs by TCM in the treatment of GT， aiming to provide a new theoretical basis for tumor therapy with TCM， expand its application in the comprehensive treatment of GT， and offer new therapeutic ideas and methods for clinical practice.

Objective:To discuss the protective effect of polygonatum odoratum polysaccharide(POP)on the mice with cisplatin-induced acute kidney injury(AKI),and to clarify its possible mechanism.Methods:Forty male C57BL/6 mice were randomly divided into control group,model group,POP group,and ferroptosis inducer Erastin combined with POP(Erastin+POP)group,and there were 10 mice in each group.The mice in POP group and Erastin+POP group were given intragastric administration of POP(400 mg·kg-1),and on the 7th day,the mice in model group,POP group,and Erastin+POP group were intraperitoneally injected with cisplatin(20 mg·kg-1)to establish the AKI models,the mice in control group were injected with the same volume of normal saline,and the mice in Erastin+POP group were intraperitoneally injected with Erastin(40 mg·kg-1)one day in advance(on the 6th day of the experiment).After 9 d,the mice were killed and the serum and kidney tissue were collected,and the levels of serum creatinine(Scr)and blood urea nitrogen(BUN)and the levels of malondialdehyde(MDA)and glutathione(GSH)in kidney tissue of the mice in various groups were detected by kit;HE staining was used to observe the pathomorphology of kidney tissue of the mice in various groups;the expression levels of ferroptosis suppressor protein 1(FSP1),ferritin heavy chain 1(FTH1),and glutathione peroxidase 4(GPX4)proteins in kidney tissue of the mice in various groups were detected by immunohistochemistry;Western blotting method was used to detect the expression levels of nuclear factor-E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins in kidney tissue of the mice in various groups.Results:Compared with control group,the levels of Scr and BUN of the mice in model group were significantly increased(P＜0.01),the level of MDA in kidney tissue was significantly increased(P＜0.01),and the level of GSH was significantly decreased(P＜0.01);most kidney tubules were dilated,the epithelial cells were swollen,the vacuolar degeneration and epithelial cells fell off,and the protein-like tubules could be seen in the lumen;the expression levels of FSP1,FTH1,GPX4,Nrf2,and HO-1 proteins in kidney tissue were decreased significantly(P＜0.05 or P＜0.01).Compared with model group,the levels of Scr and BUN of the mice in POP group were significantly decreased(P＜0.01),the level of MDA in kidney tissue was significantly decreased(P＜0.01),and the level of GSH was significantly increased(P＜0.01);the dilatation of kidney tubular lumen,epithelial cell swelling,vacuolar degeneration,and epithelial cell exfoliation were decreased;the expression levels of FSP1,FTH1,GPX4,Nrf2,and HO-1 proteins in kidney tissue of the mice in POP group were significantly increased(P＜0.05 or P＜0.01).Compared with POP group,the levels of Scr and BUN of the mice in Erastin+POP group were significantly increased(P＜0.01),the level of MDA in kidney tissue was increased(P＜0.05),and the level of GSH was significantly decreased(P＜0.01);the pathological injury of kidney tissue was aggravated obviously;the expression levels of FSP1,FTH1,GPX4,Nrf2,and HO-1 proteins in kidney tissue were significantly decreased(P＜0.05 or P＜0.01).Conclusion:POP can reduce the AKI in the mice induced by cisplatin,and its mechanism may be related to the inhibitory effect of POP on the ferroptosis induced by cisplatin.

Objective To investigate the effect and underlying mechanism of roxadustat on apoptosis and senescence of renal tubular epithelial cell line HK-2 induced by heat stress.Methods After HK-2 cells were treated with different concentrations of roxadustat(10,20,30,40 and 50 μmol/L)for 24 h,CCK-8 assay was used to determine the optimal intervention concentration of roxadustat.HK-2 cells were divided into 4 groups(n=3):control group,roxadustat group(30 μmol/L,24 h),heat-stress group(43 ℃,2 h),and heat-stress+roxadustat group(30 μmol/L roxadustat treatmnet for 24 h followed by heat-stress 2 h).Cell viability was detected by CCK-8 assay.Expression of hypoxia-inducible factor-1α(HIF-1α),Cleaved Caspase-3,p16 and p21 at protein level was detected by Western blotting.Immunofluorescence assay was employed to observe the distribution of HIF-1α.β-galactosidase staining kit was utilized to detect SA-β-Gal activity.TUNEL staining was used to measure cell apoptosis.Results The highest cell viability was observed in the cells after 30 μmol/L roxadustat treatment.Heat stress resulted in a significant decrease in cell viability(P＜0.05),elevated protein levels of HIF-1α,Cleaved Caspase-3,p16 and p21(P＜0.05),enhanced SA-β-Gal activity(P＜0.05)and increased percentage of TUNEL-positive cells(P＜0.05)when compared with the cells in the control group.In comparison with the heat-stress group,the heat-stress+roxadustat group showed significant decrease in the protein levels of Cleaved Caspase-3,p16 and p21(P＜0.05),reduced activity of SA-β-Gal[(65.44±5.00)％vs(77.15±2.61)％,P＜0.05]and decreased percentage of TUNEL-positive cells[(16.73±2.20)％vs(46.40±13.87)％,P＜0.05],but increase in cell viability[(86.33±4.51)％vs(66.33±8.50)％,P＜0.05]as well as HIF-1α protein expression(P＜0.05).Furthermore,immunofluorescence assay showed that HIF-1α was mainly distributed in the nucleus and perinucleus.Conclusion Roxadustat attenuates heat stress-induced apoptosis and senescence of renal tubular epithelial cells by upregulating HIF-1α.

Objective To explore the correlation of baseline CCL19+dendritic cell(CCL19+DC)infiltration in lung adenocarcinoma microenvironment with immunotherapy efficacy and CD8+T cell infiltration.Methods We retrospectively analyzed the data of patients with lung adenocarcinoma hospitalized at First Affiliated Hospital of Henan University of Science and Technology from January,2020 to December,2023,and collected tissue samples from 96 patients undergoing immunotherapy for assessing CCL19+DC and CD8+T cell infiltration using immunofluorescence assay.We evaluated the predictive value of baseline CCL19+DCs for patient responses to immunotherapy using receiver-operating characteristics(ROC)curves and analyzed the correlations of baseline CCL19+DC expression with immunotherapy efficacy and CD8+T cell and cytotoxic T lymphocyte(CTL)infiltrations.In co-culture systems of lung adenocarcinoma PC9 cells,CD8+T cells and DCs(overexpressing CCL19 with or without anti PD-1 antibody treatment),the expressions of granzyme B,perforin,IFN-γ,and Ki-67 in T cells were analyzed using flow cytometry.Results The patients with partial or complete remission following immunotherapy had a significantly higher baseline CCL19+DC infiltration level in lung adenocarcinoma tissues than those with poor responses.CCL19+DC infiltration had an area under ROC curve of 0.785,a sensitivity of 75.6%,and a specificity of 62.8%for predicting immunotherapy efficacy.The expression of CD8+T cell surface molecules Granzyme B(P<0.01),Perforin(P<0.01),IFN-γ(P<0.01)and Ki-67(P<0.001)in patients with high expression of CCL19+DC were higher than those in patients with low expression of CCL19+DC.The baseline CCL19+DC infiltration level was positively correlated with immunotherapy efficacy(P=0.003),CTL infiltration of(r=0.6657,P<0.001)and CD8+T cell infiltration(P=0.007).In the co-cultured cells,CCL19 overexpression combined with anti-PD1 treatment of the DCs more strongly enhanced cytotoxicity and proliferation of CD8+T lymphocytes than either of the single treatments(P<0.01 or 0.001).Conclusion The baseline CCL19+DC infiltration level in lung adenocarcinoma microenvironment is positively correlated with immunotherapy efficacy and CTL infiltration and can thus predict the response to immunotherapy.

This paper summarized Professor PENG Peichu's experience in the differentiation and treatment of prostate cancer in three phases and four stages. It is considered that prostatic cancer is categorized into root deficiency and branch excess， with depletion of healthy qi as the root， and the accumulation of cancer toxin as the minifestation. Clinical diagnosis and treatment of prostatic cancer can be divided into three phases and four stages according to the exuberance and decline of pathogenic and healthy qi and the changes of deficiency and excess of yin and yang. In the initial accumulation phase of cancer toxin （yang excess stage）， the key pathogenesis is the accumulation of dampness， heat and static blood， and internal generation of cancer toxin， and the treatment should be resolving toxins， fighting cancer and dispelling yang excess. In the phase of healthy qi deficiency and toxin accumulation （yin deficiency stage）， with the lung and kidney yin deficiency， dampness， heat and static toxin accumulation as the key pathogenesis， the treatment should be centered on mutual generation between metal and water to nourish kidney yin， supplemented with the method of clearing heat and draining dampness， activating blood and resolving toxins， for which self-made Nanbei Formula（南北方）is usually used. In the phase of yang deficiency and cold stagnation （yang deficiency stage and yin excess stage）， with the spleen and kidney yang deficiency， cold dampness stagnation， static heat and toxin accumulation as the key pathogenesis， the treatment should be warming and tonifying spleen and kidney to dissipate cold accumulation； for deficiency of both yin and yang， and excess pathogen obstruction， modified Yanghe Decoction（阳和汤） is recommended， while for yang deficiency， cold congealing and blood stasis， self-made Wenshen Sanjie Formula（温肾散结方） can be used， and for cold dampness binding with cancer toxin， and cold complex with heat， self-made Quanan Formula （泉安方） is advised.

Objective:To investigate the predictive value of fluid-attenuated inversion recovery (FLAIR) signal strength ratio (SIR) in onset time≤4.5 h in patients with acute ischemic stroke.Methods:A retrospective analysis was performed; 180 acute ischemic stroke patients admitted to Department of Neurology, Nanjing Hospital Affiliated to Nanjing Medical University from January 2020 to June 2023 were chosen. Hypoperfusion intensity ratio (HIR) was used to evaluate the collateral circulation (poor collateral circulation: HIR≤0.4; good collateral circulation: HIR>0.4); clinical data and imaging indexes between poor collateral circulation and good collateral circulation groups were compared. Univariate and multivariate Logistic regressions were used to analyze the influencing factors for onset time≤4.5 h in patients with acute ischemic stroke. Correlation between SIR and onset time was analyzed in patients with acute ischemic stroke. Role of HIR as agency between SIR and onset time was explored. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of SIR and diffusion weighted imaging (DWI)-FLAIR mismatch in onset time≤4.5 h in acute ischemic stroke patients.Results:Of the 180 patients, 100 were into the good collateral circulation group and 80 were into the poor collateral circulation group; compared with the good collateral circulation group, the poor collateral circulation group had significantly higher percentage of patients with hyperlipidemia, larger DWI infarction volume before treatment, larger perfusion weighted imaging (PWI)-DWI mismatch volume and higher SIR ( P<0.05). In these 180 patients, 76 had onset time≤4.5 h and 104 had onset time>4.5 h. Univariate Logistic regression analysis showed that hyperlipidemia, DWI infarct volume before treatment, DWI-FLAIR mismatch, HIR and SIR were influencing factors for onset time≤4.5 h in acute ischemic stroke patients ( P<0.05). Multivariate Logistic regression analysis showed that hyperlipidemia ( OR=6.654, 95% CI: 5.751-8.824, P<0.001), HIR ( OR=0.724, 95% CI: 0.521-1.321, P=0.041) and SIR ( OR=739.881, 95% CI: 383.296-14 258.065, P<0.001) were independent influencing factors for onset time≤4.5 h in acute ischemic stroke patients. Pearson correlation analysis showed that SIR was positively correlated to onset time in patients with acute ischemic stroke ( r=0.420, P<0.05), and SIR was positively correlated to onset time in patients from poor collateral circulation group ( r=0.781, P<0.05). ROC curve showed that AUC of SIR in predicting onset time≤4.5 h was 0.917 (95% CI: 0.814-1.000, P<0.001) and that of DWI-FLAIR mismatch in predicting onset time≤4.5 h was 0.530 (95% CI: 0.509-0.757, P=0.075) in poor collateral circulation group, enjoying significant difference in predictive efficacy. Conclusion:Acute ischemic stroke patients with low HIR and SIR have higher odds of onset time≤4.5 h; SIR can more accurately predict the onset time in these patients with poor collateral circulation.

Objective:To observe the effects of acupuncture and moxibustion on ubiquitin-like containing PHD and RING finger domains 1(UHRF1)and DNA methyltransferase 1(DNMT1)in ectopic endometrium of rats with endometriosis(EMS). Methods:Forty Sprague-Dawley rats were randomly divided into a sham operation group with 10 rats and a model-building group with 30 rats according to body mass.EMS rat models were established in the model-building group and then were divided into a model group,an acupuncture and moxibustion group,and a progesterone group,with 10 rats in each group.All rats were fixed by a fixator.The sham operation group and the model group were given normal saline by gavage.The acupuncture and moxibustion group received acupuncture at Xuehai(SP10)and Sanyinjiao(SP6),moxibustion at Guanyuan(CV4),and gavage of normal saline.The progesterone group was given the mixed liquid made of dydrogesterone and normal saline by gavage.After 28 d of treatments,the three diameters(length,width,and height)of EMS rats'ectopic cysts were measured,the cyst volumes were calculated,the volumes before intervention were subtracted,and the difference values were used to evaluate the growth of ectopic cysts.UHRF1 and DNMT1 mRNA and protein levels in normal endometrium,eutopic endometrium,and ectopic endometrium were detected by real-time polymerase chain reaction and immunohistochemistry. Results:There was no significant difference in the ectopic cyst volume difference between the acupuncture and moxibustion group and the progesterone group(P>0.05),but they were smaller than that of the model group(P<0.05).The levels of UHRF1 and DNMT1 mRNA and protein in the ectopic endometrium of the model group were lower than those in the normal endometrium(P<0.05).The levels of DNMT1 mRNA and UHRF1 protein in the eutopic endometrium of the model group were lower than those in the normal endometrium(P<0.05).The levels of UHRF1 mRNA and protein and the level of DNMT1 protein in the ectopic endometrium of the acupuncture and moxibustion group were higher than those in the model group(P<0.05),and the level of UHRF1 mRNA was higher than that in the progesterone group(P<0.05).The level of DNMT1 mRNA in the eutopic endometrium of the acupuncture and moxibustion group was higher than that in the model group(P<0.05).The levels of UHRF1 and DNMT1 mRNA and protein in the acupuncture and moxibustion group were insignificantly different from those in the normal endometrium(P>0.05). Conclusion:Acupuncture and moxibustion may up-regulate the levels of UHRF1 mRNA and UHRF1 and DNMT1 proteins in the ectopic endometrium to the normal level so as to reduce the volume of ectopic cysts and cure EMS in rats.

Objective To investigate the effect and mechanism of Nuanxinkang on plaque formation in obstructive sleep apnea-hypopnea syndrome(OSAHS)comorbid with atherosclerosis(AS)mice by inhibiting endothelial-to-mesenchymal transition(EndMT).Methods Male ApoE-/-mice were randomly divided into six groups:control group,model group,atorvastatin group(2.6 mg·kg-1)and Nuanxinkang low-,medium-and high-dose groups(crude drug 3.5,7.0,14.0 g·kg-1),with eight mice in each group.The mice were exposed to chronic intermittent hypoxia(CIH)environment during sleep for a long time,and fed with high-fat diet to replicate OSAHS comorbid with AS mouse model.Oil red O staining was used to observe the formation of plaque on aortic intima in mice.Masson trichrome staining was used to evaluate the collagen content of atherosclerotic plaques in the aortic root of mice.The expressions of endothelial cell marker CD31 and EndMT marker Vimentin in aortic plaque were detected by immunofluorescence.Blood lipid levels were determined by ELISA;the mRNA expression levels of EndMT markers α-SMA and Cdh2 in aortic tissue were detected by qPCR.Results Compared with the control group,the area of aortic atherosclerotic plaque in the model group was significantly increased(P＜0.01),and the area of collagen deposition in the aortic root plaque was significantly increased(P＜0.01).The number of CD31 positive cells in the plaque were significantly decreased(P＜0.01),and the number of Vimentin positive cells were significantly increased(P＜0.01).Serum TG,T-CHO and LDL-C levels were significantly increased(P＜0.01),and HDL-C level was significantly decreased(P＜0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue were significantly increased(P＜0.01).Compared with the model group,the area of aortic atherosclerotic plaque in Nuanxinkang groups were significantly reduced(P＜0.05,P＜0.01),and the collagen deposition area of aortic root atherosclerotic plaque were significantly reduced(P＜0.05,P＜0.01).The number of CD31 positive expression cells in the plaque of Nuanxinkang high-dose group were significantly increased(P＜0.05),and the number of Vimentin positive expression cells in the plaque of Nuanxinkang medium-and high-dose groups were significantly decreased(P＜0.05,P＜0.01).The serum TG level of mice in the high-dose group of Nuanxinkang was significantly decreased(P＜0.01).The serum T-CHO and LDL-C levels of mice in each Nuanxinkang administration group were significantly decreased(P＜0.05,P＜0.01).The serum HDL-C levels of mice in the medium-and high-dose groups of Nuanxinkang were significantly increased(P＜0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue of mice in each treatment group were significantly decreased(P＜0.01).Conclusion Nuanxinkang can effectively reduce the plaque formation in OSAHS comorbid with atherosclerosis mice,which may be related to its inhibition of EndMT and reduction of collagen fiber formation.