AIM:To evaluate the immediate effect of vocal training on tear film stability in patients with dry eye disease.METHODS:A prospective crossover controlled study. From April 1 to April 20, 2026, volunteers with mild-to-moderate dry eye [Ocular Surface Disease Index-6(OSDI-6)score: 4-8] were enrolled. Participants were randomly allocated into two groups to receive two interventions in different sequences. Group A underwent a 50-min standardized vocal training session during the first intervention, while Group B served as a blank control; The two groups crossed over to the alternative intervention for the second session, with a 1-week washout period between the two interventions. The immediate post-intervention changes in Dry Eye Symptoms Questionnaire(CDES-Q)score, pre-and post-intervention non-invasive tear film breakup time(NIBUT), including first NIBUT and average NIBUT, as well as tear meniscus height(TMH), were recorded for each session.RESULTS:A total of 32 eligible participants(64 eyes)were enrolled and completed the study per protocol. The participants were randomly assigned to two groups with different intervention sequences. Group A(16 participants, 32 eyes)comprised 3 males and 13 females, with a mean age of 61.69±4.56 y and a mean OSDI-6 score of 5.750±1.183. Group B(16 participants, 32 eyes)comprised 3 males and 13 females, with a mean age of 63.19±1.56 y and a mean OSDI-6 score of 5.250±1.438.There were no significant differences in baseline characteristics between the two groups(P>0.05). After vocal training intervention, the net effect size for first NIBUT was 1.883 s(P=0.042), and for average NIBUT was 2.076 s(P=0.019). No significant change was observed in TMH(P=0.652). The CDES-Q score difference was -47.188(P<0.001). Further individual data analysis revealed that 59% of participants exhibited prolonged first NIBUT and 50% exhibited prolonged average NIBUT after vocal training.CONCLUSION: Vocal training can immediately improve tear film stability. This therapeutic approach shows promise for dry eye management and provides a reference for future large scale and long-term investigations.

Objective: To analyze the infection characteristics of newly reported HIV/AIDS cases in Hangzhou City, so as to provide the reference for effective AIDS intervention. Methods: Newly reported HIV/AIDS cases in Hangzhou City in 2022 were recruited. Demographic information, HIV testing status, infection routes and sexual behaviors were collected using questionnaire surveys. Blood samples were collected before antiviral treatment, and HIV-1 pol gene sequences were detected to construct molecular transmission networks. The characteristics of HIV/AIDS cases, including infection routes, time, and location were analyzed. Factors affecting infection time and location among HIV/AIDS cases were analyzed using a multivariable logistic regression model. Results: A total of 1 007 HIV/AIDS cases were reported in Hangzhou City in 2022, with 907 cases (90.07%) completing questionnaire surveys. Among them, 833 were males (91.84%), and 532 had out-of-province household registrations (58.65%). Ninety-one molecular transmission networks were established, and 276 cases were involved, with homosexual contact as the main infection route (199 cases, 72.10%). There were 311 recently infected cases (35.34%) and 569 previously infected cases (64.66%) among 880 cases whose infection time could be determined. There were 531 locally infected. cases (70.24%) and 225 imported cases (29.76%) among 756 cases whose infection location could be determined. Multivariable logistic regression analysis showed that the HIV/AIDS cases who were identified through voluntary counseling and testing (OR=1.826, 95%CI: 1.055-3.175) and sought sexual partners through homosexual dating apps (OR=2.461, 95%CI: 1.193-5.234) were more likely to be recently infected; the cases who lived in Hangzhou City for more than one year (>1 to 5 years, OR=2.853, 95%CI: 1.552-5.358; >5 years, OR=3.534, 95%CI: 1.382-9.804), sought sexual partners through entertainment venues (OR=3.449, 95%CI: 1.390-8.935), online/social apps (OR=2.416, 95%CI: 1.084-5.488) and homosexual dating apps (OR=3.734, 95%CI: 1.677-8.493) were more likely to be locally infected; student cases were more likely to be infected outside Hangzhou City (OR=0.115, 95%CI: 0.019-0.525). Conclusions The newly reported HIV/AIDS cases in Hangzhou City in 2022 were primarily infected through homosexual contact, previously and locally. Seeking sexual partners through homosexual dating apps is an important influencing factor for recent and local infections, highlighting the need for strengthening traceback investigations of related cases.

This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such patients.

AIM To investigate the effects of Wenfei Jiangzhuo Formula on mitochondrial function of Aβ25-35-induced BV-2 cells.METHODS In the establishment of cell model of Alzheimer's disease(AD)using Aβ25-35 on the BV-2 cells,the optimal concentration and time point of Aβ25-35 intervention were determined;and the groups for the intervention of LFHP-1c group(inhibitor)or the serum containing Wenfei Jiangzhuo Formula were set up.The detection of the optimal intervention concentration and time point by CCK-8 assay;the observation of cell migration and apoptosis by Transwell assay and Hoechst 33342 staining;the detection of the positive expressions of PGAM5 and Drp1 by immunofluorescence;and the detection of cellular PGAM5,Drp1,OPA1,and Mfn1/2 mRNA and protein expressions by RT-qPCR and Western blot were conducted.RESULTS The best AD cell model was established by 48 h exposure to 5 μmol/L of Aβ25-35,and most active cell viability was achieved with the 48 h use of serum containing 20％Wenfei Jiangzhuo Formula.Compared with the control group,the model group displayed decreased number of cell migration,more bright blue positive apoptotic cells,increased number of PGAM5 and Drp1 positive cells and their mRNA and protein expressions(P＜0.05);and decreased mRNA and protein expressions of OPA1 and Mfn1/2(P＜0.05).Compared with the model group,the groups intervened with the medicines shared increased number of cell migration,less bright blue positive apoptotic cells,decreased number of PGAM5 and Drp1 positive cells and their mRNA and protein expressions(P＜0.05);and elevated OPA1 and Mfn1/2 mRNA and protein expressions(P＜0.05).CONCLUSION Wenfei Jiangzhuo Formula exerts cerebroprotective effects to improve cognition by reducing cell damage and improving the balance of mitochondrial homeostasis through PGAM5-Drp1 axis in AD model.

Objective:To investigate the effect and safety of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) in treating the chronic pancreatitis (CP) patients with main pancreatic duct (MPD) stones and to analyze the influencing factors of success of lithotripsy.Methods:Clinical data of 132 patients with CP complicated with MPD stones treated with P-ESWL in the Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2022 to December 2023 were retrospectively analyzed, including 103 males and 29 females, aged (50.3±16.9) years. The times of P-ESWL, the success rate of stone fragmentation, the necessity of combining endoscopic retrograde cholangiopancreatograhy (ERCP), clearance rate of MPD stones, and incidence of post-P-ESWL complications (acute pancreatitis, abdominal hematoma, infection, steinstrasse, perforation, etc.) were evaluated. The factors influencing the success rate of lithotripsy were analyzed using univariate and multivariate logistic regression.Results:All patients underwent P-ESWL treatment, with (2.23±0.82) times of P-ESWL per person. The success rate of stone fragmentation was 87.1%(115/132). Of 107 CP patients (81.1%, 107/132) were treated with their first P-ESWL. Of 12 patients (9.1%, 12/132) underwent single P-ESWL, and 120 (90.9%, 120/132) underwent P-ESWL combined with ERCP. There were 95 cases (72.0%, 95/132) with effective removal of stones, and 62 (47.0%, 62/132) with complete removal of stones. Post-P-ESWL complications included eight cases (6.1%, 8/132) of acute pancreatitis, two (7.6%, 2/132) of steinstrasse complicated with acute pancreatitis and one (0.8%, 1/132) of abdominal hematoma. No infection or perforation occurred. Multivariate logistic regression analysis showed that the higher CT value of stones ( OR=1.239, 95% CI: 1.040-1.477, P=0.017) was associated with the lower success rate of stone fragmentation. Conclusion:P-ESWL is safe and effective in treating patients with CP complicated with MPD stones. The CT value of stones is a risk factor for the success rate of P-ESWL.

Objective To design a performance testing platform to evaluate the working status and performance characteristics of the ventilator proportional solenoid valve.Methods The performance testing platform had its hardware including a high-pressure gas source,a pressure regulating valve,sensors and etc,and its software designed based on PyQt5 and composed of several modules for data acquisition,parameter setting,image display,indicator computation,result output and etc.Two kinds of proportional solenoid valves(Valve 1、Valve2)were selected for static and dynamic tests to verify the performance of the platform.Results The platform developed facilitated the proportional solenoid valve to carry out accurate computation of static and dynamic indicators at real time and time domain and waveform feature extraction of sensor data by precision control and data acquisition for the proportional solenoid valve.Static tests showed that Valve 1 gained advantages over Valve 2 in static flow characteristics involving in lowered repeatability,return error and offset while enhanced stability;dynamic tests indicated Valve 2 had rapid flow variations and significant flow fluctuation impacts,Valve 1 showed smooth dynamic response changes,and Valve 2 behaved better than Valve 1 in dynamic performance.Conclusion The testing platform developed comprehensively demonstrates the performance characteristics and working performance of the ventilator proportional solenoid valve,which is of great significance to enhance the reliability and safety of the ventilator.[Chinese Medical Equipment Journal,2025,46(1):13-19]

OBJECTIVE: To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma. METHODS: In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously. RESULTS: In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01). CONCLUSIONS Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.
Aristolochic Acids/toxicity* ; Animals ; Humans ; NAD(P)H Dehydrogenase (Quinone)/genetics* ; HEK293 Cells ; Kidney/pathology* ; Cytochrome P-450 CYP1A2/genetics* ; Mice, Inbred C57BL ; DNA Adducts/drug effects* ; Male ; Kidney Diseases/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Prunus armeniaca ; Plant Extracts

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*