ObjectiveTo observe the clinical efficacy and safety of Zhinao capsules in the treatment of mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. MethodsA randomized， double-blind， placebo， controlled clinical trial design was adopted， and 60 Alzheimer's disease patients aged 50-85 years with mild and moderate sleep disorders due to spleen-kidney deficiency and combined phlegm and stasis were included. According to the randomized numble table method， the patients were assigned into a treatment group and a control group （30 in each group， with 29 patients in the treatment group and 28 patients in the control group finally completing the trial）. The treatment group was treated with donepezil hydrochloride tablets combined with Zhinao capsules， and the control group was treated with donepezil hydrochloride tablets combined with the simulant of Zhinao capsules for 12 weeks. The Pittsburgh sleep quality index （PSQI）， smart bracelet sleep monitoring， epworth sleeping scale （ESS）， Mini-Mental State Examination （MMSE）， Activities of Daily Living （ADL）， and traditional Chinese medicine symptoms were scored. Furthermore， the brain-derived neurotrophic factor （BDNF） and gamma-aminobutyric acid （GABA） levels were measured. ResultsAfter 12 weeks of treatment， the total response rate of clinical efficacy assessment in the treatment group reached 89.7%， which was significantly higher than that （21.4%） in the control group （Z=-5.14， P<0.01）. After treatment， the TCM symptom scores declined in both groups （P<0.01）， and the scores in the treatment group were lower than those in the control group （P<0.01）. After treatment， the treatment group showed decreased total score and seven component scores of the PSQI scale （P<0.05， P<0.01）， and the scores in the treatment group were lower than those in the control group （P<0.05， P<0.01）. After treatment， the treatment group showed increases in the duration of deep sleep， light sleep， rapid eye movement sleep， and total sleep at night and decreases in the time to fall asleep， the number of awakenings from sleep at night， and the time for sporadic daytime naps （P<0.01）. The control group did not show significant changes in the duration of light sleep， time to fall asleep， and number of awakenings from sleep at night. Moreover， the treatment group outperformed the control group in terms of the indicators above （P<0.05， P<0.01）. After treatment， the treatment group showed decreased scores of ESS， ADL and its subscales physical self-maintenance scale （PSMS）， and Instrumental Activities of daily living scale （IADLs） and increased score of MMSE and levels of BDNF and GABA （P<0.05， P<0.01）. There was no significant difference in PSMS between the two groups， and the treatment group was significantly better than the control group in terms of the rest of the above indicators （P<0.05， P<0.01）. Patients in neither groups complained of uncomfortable symptoms. ConclusionZhinao capsules have significant clinical efficacy in treating patients with mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. Zhinao capsules can significantly reduce PSQI， ESS， and ADL scores， increase the MMSE score and the expression of BDNF and GABA， effectively optimize the structure of sleep， improve the intelligence， and enhance the ability of daily life， without causing uncomfortable symptoms. The mechanism may be related to the increase in the expression of sleep/wake-related neurotransmitters.

ObjectiveTo observe the clinical efficacy and safety of Zhinao capsules in the treatment of mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. MethodsA randomized， double-blind， placebo， controlled clinical trial design was adopted， and 60 Alzheimer's disease patients aged 50-85 years with mild and moderate sleep disorders due to spleen-kidney deficiency and combined phlegm and stasis were included. According to the randomized numble table method， the patients were assigned into a treatment group and a control group （30 in each group， with 29 patients in the treatment group and 28 patients in the control group finally completing the trial）. The treatment group was treated with donepezil hydrochloride tablets combined with Zhinao capsules， and the control group was treated with donepezil hydrochloride tablets combined with the simulant of Zhinao capsules for 12 weeks. The Pittsburgh sleep quality index （PSQI）， smart bracelet sleep monitoring， epworth sleeping scale （ESS）， Mini-Mental State Examination （MMSE）， Activities of Daily Living （ADL）， and traditional Chinese medicine symptoms were scored. Furthermore， the brain-derived neurotrophic factor （BDNF） and gamma-aminobutyric acid （GABA） levels were measured. ResultsAfter 12 weeks of treatment， the total response rate of clinical efficacy assessment in the treatment group reached 89.7%， which was significantly higher than that （21.4%） in the control group （Z=-5.14， P<0.01）. After treatment， the TCM symptom scores declined in both groups （P<0.01）， and the scores in the treatment group were lower than those in the control group （P<0.01）. After treatment， the treatment group showed decreased total score and seven component scores of the PSQI scale （P<0.05， P<0.01）， and the scores in the treatment group were lower than those in the control group （P<0.05， P<0.01）. After treatment， the treatment group showed increases in the duration of deep sleep， light sleep， rapid eye movement sleep， and total sleep at night and decreases in the time to fall asleep， the number of awakenings from sleep at night， and the time for sporadic daytime naps （P<0.01）. The control group did not show significant changes in the duration of light sleep， time to fall asleep， and number of awakenings from sleep at night. Moreover， the treatment group outperformed the control group in terms of the indicators above （P<0.05， P<0.01）. After treatment， the treatment group showed decreased scores of ESS， ADL and its subscales physical self-maintenance scale （PSMS）， and Instrumental Activities of daily living scale （IADLs） and increased score of MMSE and levels of BDNF and GABA （P<0.05， P<0.01）. There was no significant difference in PSMS between the two groups， and the treatment group was significantly better than the control group in terms of the rest of the above indicators （P<0.05， P<0.01）. Patients in neither groups complained of uncomfortable symptoms. ConclusionZhinao capsules have significant clinical efficacy in treating patients with mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. Zhinao capsules can significantly reduce PSQI， ESS， and ADL scores， increase the MMSE score and the expression of BDNF and GABA， effectively optimize the structure of sleep， improve the intelligence， and enhance the ability of daily life， without causing uncomfortable symptoms. The mechanism may be related to the increase in the expression of sleep/wake-related neurotransmitters.

ObjectiveTo explore the mechanism through which Gantou Fumu decoction （GDFMT）-containing serum inhibits the activation of hepatic stellate cells. MethodsSerum pharmacology techniques were employed to prepare GDFMT-containing serum samples. Rat hepatic stellate cells （HSCT6） were randomly allocated into three groups： Control， penicillamine （90 mg·kg^-1）， and GDFMT （6.8 g·kg^-1）. Cell viability was assessed by the cell counting kti-8 （CCK-8） assay， intracellular ROS levels were determined by flow cytometry using the DCFH‑DA fluorescent probe and while extracellular collagen Ⅰ （ColⅠ） levels were quantified via enzyme linked immunosorbent assay （ELISA）. Intracellular α-smooth muscle actin （α-SMA） expression was visualized through immunofluorescence staining. Real-time polymerase chain reaction（Real-time PCR） and Western blot were performed to evaluate alterations in the expression of nuclear factor-erythroid 2-related factor 2 （Nrf2）， glutamate cysteine ligase， catalytic （GCLC）， glutamate-cysteine ligase， modifier subunit （GCLM）， Kelch-like ECH-associated protein 1 （Keap1）， NAD（P）H：Quinone oxidoreductase 1 （NQO1）， and heme oxygenase-1 （HO-1）. Genetic knockdown of Nrf2 was achieved through small interfering （siRNA） transfection to validate pathway specificity. ResultsCCK-8 data indicated that under the selected experimental conditions， culturing HSCT6 cells with 10% （volume fraction） GDFMT-containing serum for 48 h demonstrated equivalent effect in inhibiting HSCT6 cell proliferation compared with culturing HSCT6 cells with 10% （volume fraction） penicillamine-containing serum for 36 h， with no statistically significant difference between the two groups. After treatment of HSCT6 cells with siRNA-mediated Nrf2 gene transfection technique， the inhibitory effect of GDFMT on the activation process of HSCT6 cells was significantly weakened. After HSCT6 cells were cultured with GDFMT-containing serum for 48 h， the flow cytometry with a fluorescence probe showed that the content of reactive oxygen species （ROS） in the cells was significantly reduced. After the expression level of the Nrf2 gene in HSCT6 cells was knocked down by siRNA transfection， the content of ROS increased （P<0.01）， indicating that GDFMT significantly reduced the ROS level in activated HSCT6 cells， and this effect strictly depended on the integrity of the Nrf2 pathway. Quantitative analysis by ELISA showed that the synthesis of ColⅠ in the HSCT6 cell culture system treated with GDFMT-containing serum for 48 h was lower than that in the control group （P<0.01）. After the Nrf2 gene level of HSCT6 cells was knocked down by siRNA transfection， the ColⅠ concentration in the culture supernatant increased （P<0.01）. The results of α-SMA detection by IF method showed that compared with the normal group， GDFMT-containing serum reduced the expression of α-SMA （P<0.01） and the protein level of α-SMA in HSCT6 cells was increased （P<0.01） after siRNA-mediated Nrf2 silencing， suggesting that Nrf2 signaling pathway may be involved in regulating the phenotypic transformation process of the cells. Real-time PCR and Western blot results showed that GDFMT-containing serum reduced the protein level of α-SMA （P<0.01） and enhanced the gene and protein levels of Nrf2 in the nucleus and GCLC， HO-1， Keap1， GCLM， and NQO1 in the cytoplasm of HSCT6 cells （P<0.05， P<0.01）. After the Nrf2 gene level of HSCT6 cells was knocked down by siRNA transfection， the protein level of α-SMA was increased （P<0.01）， and the levels of GCLC， GCLM， Keap1， NQO1， and HO-1 were decreased （P<0.05， P<0.01）. These results indicated that GDFMT-containing serum successfully triggered the Nrf2 signaling pathway of HSCT6 cells. ConclusionThe anti-hepatic fibrosis effect of 10%GDFMT was equivalent to that of penicillamine. In addition， GDFMT can inhibit HSC activation and reduce oxidative stress damage by activating the Nrf2/antioxidant response element （ARE） pathway， as manifested by the up-regulated expression of Nrf2 and downstream antioxidant genes （GCLC， GCLM， HO-1， Keap1， and NQO1） and reduced secretion of ROS， α-SMA， and ColⅠ.

Objective To investigate the value of serum thymidine kinase 1(TK1),hypoxia-inducible fac-tor-1α(HIF-1α)and squamous cell carcinoma antigen(SCC)in the diagnosis and prognosis of esophageal cancer.Methods A total of 105 patients with esophageal cancer treated in the Qinhuai Medical Zone of East-ern Theater General Hospital from February 2019 to October 2021 were selected as the study group,and 80 healthy subjects were selected as the control group during the same period.The serum levels of TK1,HIF-1αand SCC were compared between study group,control group and patients with different pathological charac-teristics.Patients with esophageal cancer were followed up for 3 years,and the overall survival(OS)and pro-gression-free survival(PFS)were recorded.Receiver operating characteristic curve was used to analyze the di-agnostic efficiency of serum TK1,HIF-1α and SCC combined detection for esophageal cancer,Pearson correla-tion analysis was used to analyze the correlation between the serum indicators,and Kaplan-Meier survival a-nalysis was used to analyze the OS and PFS of patients with different serum levels of TK1,HIF-1α and SCC.Multivariate COX regression was performed to analyze prognostic factors.Results Compared with the control group,the serum TK1,HIF-1α and SCC levels in the study group increased(P＜0.05).The area under the curve(AUC)of serum TK1,HIF-1α,SCC alone and combined for diagnosis of esophageal cancer were 0.893,0.744,0.841,0.922,respectively,and their combined diagnoses of esophageal cancer had the largest AUC.Se-rum TK1,HIF-1α and SCC in patients with different TNM stages and differentiation stages were significantly different(P＜0.05).Serum TK1,HIF-1α and SCC in patients with lymph node metastasis were higher than those without lymph node metastasis(P＜0.05).Serum TK1 was positively correlated with HIF-1α and SCC levels in patients with esophageal cancer(P＜0.05).The survival functions of OS and PFS in TK1,HIF-1αand SCC low expression group were better than those in high expression group(P＜0.05).Multivariate COX regression analysis showed that low differentiation and lymph node metastasis were independent risk factors for poor prognosis in esophageal cancer patients(P＜0.05).Conclusion Serum levels of TK1,HIF-1α and SCC are increased in patients with esophageal cancer,the combined diagnosis of the three is effective.The high expression of TK1 and HIF-1αand SCC will shorten OS and PFS.

In September 2024,the updated version of Chinese Clinical Practice Guidelines for Hypertension was published.This version of guidelines comprises 44 pivotal clinical inquiries and 99 recommendations pertaining to the diagnosis,assessment,and management of hypertension.The new version of the guidelines emphasizes moving the line of defense of antihypertensive treatment forward,strengthening antihypertensive treatment,reflecting the concept of strengthening initial prevention and primary prevention,and stressing the importance of lifestyle interven-tion and blood pressure monitoring,which is of great guiding value and practical significance to clinical work.This paper interprets the management strategy of hypertension patients from the perspective of nursing practice,in order to provide evidence-based guidance for clinical nursing work.

Objective To investigate the factors influencing the development of extra-pulmonary tuberculosis(EPTB)in patients with viral hepatitis complicated by pulmonary tuberculosis(PTB).Methods A retrospective analysis was conducted on 427 patients with Hepatitis B Virus(HBV)and Hepatitis C Virus(HCV)infections complicated by PTB admitted to the tuberculosis department of Kunming Third People's Hospital from January 2015 to December 2020.Patients were divided into the EPTB complication group(n=72)and the non-EPTB complication group(n=355)based on the presence of EPTB.Clinical treatment data of patients were collected.Univariate and multivariate Logistic regression analyse were used to screen independent risk factors for EPTB as predictive factors.A nomogram prediction model was established for Extrapulmonary Tuberculosis(EPTB)complications in patients with viral hepatitis and Pulmonary Tuberculosis(PTB),evaluated using the Hosmer-Lemeshow test and ROC curve analysis.Results Among the 427 patients,292(68.3%)were male and 135(31.7%)were female,with 72 cases of EPTB,resulting in an incidence rate of 16.86%.In the EPTB group,there were 34 males(47.2%)and 38 females(52.8%).The types of EPTB included tuberculous pleuritis(21 cases,29%),tuberculous peritonitis(16 cases,22%),lymph node tuberculosis(13 cases,18%),tuberculous encephalitis(5 cases,6%),intestinal tuberculosis(6 cases,8%),bone tuberculosis(5 cases,6%),pelvic tuberculosis(3 cases,4%),and genitourinary tuberculosis(3 cases,4%).Multivariate logistic regression analysis showed that gender(OR=0.425,95%CI:0.250-0.722,P=0.02),low triglyceride(TG)levels(OR=0.837,95%CI:0.717-0.978,P=0.025),the tuberculosis-specific antigen A(ESAT-6)(OR=1.007,95%CI:1.003～1.011 were independent influencing factors for EPTB in patients with PTB complicated by HBV and HCV infections.The optimal cutoff value for the nomogram model is 0.192,with a sensitivity of 0.611,specificity of 0.710,Youden index of 0.741,positive likelihood ratio of 2.103,and negative likelihood ratio of 0.548.The Hosmer-Lemeshow test yielded χ2=2.631,P=0.955.ROC curve analysis showed an AUC of 0.693,95%CI:0.629 1～0.7574.Conclusion The prediction model based on gender,low TG levels and ESAT-6 can well predict the occurrence of EPTB to some extent,providing a reference for clinical treatment.

Objective To evaluate the relationship between nutritional parameters and the risk of venous thromboembolicism(VTE)in patients with tuberculosis so as to identify the risk factors and predictors of thrombosis and assist in the early identification of high-risk factors for VTE in patients with the pulmonary tuberculosis.Methods A total of 323 patients diagnosed with the pulmonary tuberculosis and hospitalized in Kunming Third People's Hospital from August 2021 to August 2023 were collected.According to the VTE risk assessment of non-operative patients,they were divided into the high-risk group and the low-risk group respectively with 116 and 207 in each group.The nutritional indicators with statistically significant differences between the two groups were screened by Lasso regression.Multivariate Logistic regression was used to screen the independent risk factors for high VTE risk in pulmonary tuberculosis patients,and a nomogram prediction model was constructed.The prediction model was evaluated by receiver operating characteristic curve(ROC),calibration curve,decision curve,and influence curve.Results Patients in the high-risk group were significantly older than those in the low-risk group(59 vs.41,P<0.001),hypertension,gender,and Type 2 diabetes did not differ significantly(P values were 0.084,0.724 and 0.488,respectively).9 variables were selected from the inter-group comparison and Lasso regression,including ALB,HCT,NRS2002 scores,HBDH,RDW-SD,RDW-CV,TG,CONUT scores,and NEFA.Multivariate Logistic regression analysis showed that ALB,NRS2002 scores,RDW-SD,and CONUT scores were independent influencing factors for the high risk of VTE scores in patients with tuberculosis(P<0.005).Area under the ROC curve showed that the AUC(0.892)for high-risk VTE scores in patients with the pulmonary tuberculosis was greater than that of ALB(0.803),NRS2002 score(0.735),RDW-SD(0.685),and CONUT score(0.774).Fitting prediction model:Logit(P):Y=0.433×NRS-0.136×ALB+0.411×CONUT score+0.072×RDW-SD-1.770,P=1/(1+e-Y)(Y:prediction index,P:prediction probability).Calibration curve showed that the model prediction tended to be consistent with the actual results(U:>0.05),and the decision curve and influence curve showed that the model can bring clinical benefits.Conclusion ALB,NRS2002 scores,RDW-SD,and CONUT scores are independent influencing factors for the high risk of VTE scores in patients with tuberculosis.They can guide the clinical practice,improve these indicators as soon as possible,reduce VTE scores,and reduce the thrombosis risk.At the same time,the prediction model performs well in the verification cohort,with its discrimination ability,calibration accuracy and clinical utility(decision curve analysis)all reaching a satisfactory level.

Objective:To develop a deep learning model based on 3D super-resolution reconstruction technology and to analyze its feasibility and effectiveness in predicting paraglottic space invasion in hypopharyngeal cancer.Methods:A retrospective study was conducted involving 382 patients with hypopharyngeal squamous cell carcinoma treated at Qilu Hospital of Shandong University between January 2014 and December 2020. The cohort included 364 males and 18 females, with a mean age of 62±7 years. Patients were divided into a training set ( n=300) and a test set ( n=82) based on enrollment time. A generative adversarial network was used to perform 3D super-resolution reconstruction on contrast-enhanced CT images, improving spatial resolution by 16 times. A 2.5D deep learning strategy was employed to construct Resnet-NR and Resnet-SR models based on conventional and super-resolution images, respectively, to predict whether the paraglottic space was invaded. Model performance was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). A multi-reader multi-case study was conducted to assess the impact of the artificial intelligence (AI) model on clinicians′ diagnostic capabilities. Results:The super-resolution model Resnet-SR achieved the highest accuracy in both the training set (AUC=0.87, 95% CI: 0.84-0.90) and the test set (AUC=0.88, 95% CI: 0.81-0.96), significantly outperforming traditional clinical indicators (T stage, N stage, tumor diameter, and pathological differentiation degree) (AUC range: 0.55-0.70, all P<0.05). In comparison, the conventional-resolution model Resnet-NR achieved AUCs of 0.81 (95% CI: 0.77-0.84, P=0.005) and 0.80 (95% CI: 0.71-0.89, P=0.184) in the training and test sets, respectively. Using Resnet-SR to assist clinical decision-making improved the diagnostic accuracy of junior physicians (AUC=0.793 without AI assistance vs. AUC=0.871 with AI assistance, P=0.012) and significantly reduced diagnosis time for clinicians of all experience levels (86.5 s without AI assistance vs. 82.5 s with AI assistance, t=2.01, P=0.032). Conclusion:This study successfully develops a deep learning model based on 3D super-resolution reconstruction technology, which can assist in preoperative prediction of paraglottic space invasion in hypopharyngeal cancer. The AI-assisted tool improves diagnostic accuracy for junior physicians and enhances diagnostic efficiency for clinicians across all experience levels.

Objective To predict the potential distribution area of Halenia elliptica under current and future climate conditions;To provide a foundation for the sustainable utilization and cultivation of H.elliptica resources.Methods Based on 116 occurrence records and 36 environmental variables,this study employed correlation analysis and contribution rates to identify 10 key environmental factors of H.elliptica.The MaxEnt model,combined with Geographic Information Systems(GIS),was used to predict the potential suitable areas for H.elliptica under current and different future climate scenarios,and centroid shift analysis was performed using SDM_toolbox.Results The MaxEnt model predicted accurately,with an area under the receiver operating characteristic(ROC)curve of 0.968.Altitude,annual precipitation and mean temperature of the coldest season were identified as the primary influencing factors.The current suitable area for H.elliptica was approximately 176.04×104 km2.In the future climate conditions,the suitable habitat of H.elliptica will be moderately adjusted,especially in Sichuan and Xizang.Conclusion In the future,the suitable potential distribution areas for H.elliptica in China will increase,and there will be slight differences in the increment of different suitable potential distribution areas.This study can provide a basis for resource conservation and sustainable utilization,and highlight the importance of dynamic ecological monitoring in the context of global warming.

Objective To investigate the value of low tube voltage and low dose contrast agents combined with artificial intelligence iterative reconstruction(AIIR)in upper limb CT angiography(CTA)for displaying arteriovenous fistula(AVF).Methods Totally 65 patients with chronic renal failure and suspected AVF stenosis who underwent upper limb CTA were prospectively enrolled and randomly divided into conventional-dose group(CD group,n=30)and low-dose group(LD group,n=35).In CD group,CTA was acquired using conventional tube voltage(100 kVp)and contrast agents dosage(1.0 ml/kg body mass),and conventional hybrid iterative reconstruction(HIR)was used to reconstruct images(group A),while in LD group,CTA was collected using 80 kVp and contrast agent dosage of 0.6 ml/kg body mass,and images were reconstructed with HIR(group B)and AIIR(group C),respectively.Then subjective and objective assessment of imaging quality were performed,respectively,the results were compared among groups,while the radiation dose and dosage of contrast agents were compared between CD and LD groups.Results No significant difference of subjective score of imaging quality nor confidence for diagnosing AVF stenosis was found between group A and group C(both P＞0.017),and all the above scores were higher than those in group B(all P＜0.017).Signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of subclavian artery,brachial artery and radial artery in group C were all higher than those in groups A and B(all P＜0.017),while no significant difference of SNR nor CNR was found between group A and B(all P＞0.017).The volume CT dose index,dose length product and dosage of contrast agent in LD group were all lower than those in CD group(all P＜0.001).Conclusion Low tube voltage and low dose contrast agents combined with AIIR in upper limb CTA for displaying AVF could reduce radiation dose and contrast agents dosage under the condition of ensuring imaging quality.