OBJECTIVE To establish the fingerprints of Tianma jiannao granules （TJG） and the method for content determination to evaluate the quality of TJG comprehensively combined with chemometric analysis. METHODS High-performance liquid chromatography （HPLC） was used to establish the fingerprints of 13 batches （S1-S3） of TJG and determine the contents of inosine， gastrodin， parishin B and parishin E. Cluster analysis， principal component analysis， and orthogonal partial least squares- discriminant analysis were performed using SPSS 20.0 and SIMCA 18 software； using variable importance projection （VIP） value greater than 1 as a criterion， marker components that affected quality were screened. RESULTS A total of 28 common peaks were identified in the 13 batches of TJG with similarities greater than 0.9， and 7 common peaks were identified， which were gastrodin， p-hydroxybenzyl alcohol， parishin B， parishin E， rhynchophylline， inosine and salidroside. The 13 batches of TJG were clustered into 3 categories， S1-S2， S8-S10 and S12 were clustered into one category； S3 and S7 were clustered into one category； S4-S6， S11 and S13 were clustered into one category. VIP of inosine was greater than 1. The contents of inosine， gastrodin， parishin B and parishin E were 62.637-176.677， 17.821-37.642， 5.748-16.077 and 5.660-13.510 μg/g. CONCLUSIONS The established HPLC fingerprints and content determination method are stable， reliable and highly reproducible， which can be used to evaluate the quality of TJG in combination with chemometric analysis. Inosine may be a marker component that affects the quality of TJG. There are differences in the quality of 13 batches of TJG.

Objective: To analyze the current status of latent tuberculosis infection (LTBI) among freshmen in boarding middle schools in Longgang District, Shenzhen, so as to provide reference for formulating tuberculosis prevention and control strategies in the next stage. Methods: Data for tuberculosis health examination conducted among primary and secondary school students in Longgang District of Shenzhen in September 2022 to May 2023 were utilized to analyze the latent tuberculosis infection rate, and to explore the differences in latent tuberculosis infection rate among different grades, school nature, school categories and school levels. Results: The latent tuberculosis infection rate among freshmen in boarding secondary schools in Longgang District, Shenzhen in 2022 was 2.45%. The infection rate among full middle school (6.45%) and high school (3.37%) were higher than that in boarding junior high school (0.28%), nine year education school (0) and twelve year education school (1.00%) ( P <0.01). Moreover, the infection rate of high school freshmen (2.68%) was higher than that of bording junior high school (0.33%), and the rate of public schools (2.87%) and municipal schools (3.24%) were higher than those of private schools (1.78%) and distric-level schools (2.13%) respectively, with statistical significance observed for all differences( χ 2=43.58, 25.15, 22.69, P <0.01). Conclusions The latent tuberculosis infection rate among new boarding secondary students is relatively low in Longgang District of Shenzhen. However, the infection rate is higher in high school, public and municipal school. School should fully guarantee sports participation of students, enhance students awareness of tuberculosis through health knowledge lectures, and reduce the incidence of tuberculosis among students.

Objective:To explore the predictive value of pulmonary effective arterial elastance (Ea) in patients with heart failure (HF).Methods:This is a retrospective cohort study, which retrospectively included 284 patients with HF who underwent right heart catheterization at Heart Failure Center in Fuwai Hospital between September 2013 and February 2022. Data regarding baseline clinical characteristics, hemodynamic profiles, and prognosis were collected. Ea was calculated as mean pulmonary arterial pressure/stroke volume. Patients were divided into Ea<0.555 group and Ea≥0.555 group according to the median value of Ea (0.555 mmHg/ml, 1 mmHg=0.133 kPa). The primary outcome was the primary clinical event, set as the first occurrence of a series of composite events, including all-cause death, heart transplantation, left ventricular assist device implantation, and HF rehospitalization. Event-free survival was defined as the absence of primary clinical events. Spearman correlation analysis was used to calculate the correlation coefficient between Ea and parameters reflective of right heart function. The Kaplan-Meier analysis was used to compare the different groups for the estimation of outcomes with the log-rank test. We used Cox proportional-hazards regression models to estimate hazard ratios ( HR) for primary clinical event. Subgroup analysis was performed based on the age, gender, New York Heart Association (NYHA) functional class, left ventricular ejection fraction, presence of pulmonary hypertension, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) values. We used receiver operating characteristic (ROC) curve to calculate the area under the curve ( AUC) of Ea for predicting event-free survival in patients with HF. Results:The median age was 51 years, and 206 (72.5%) patients were male. Ea and pulmonary vascular resistance (PVR) were significantly correlated ( r=0.698, P<0.001). The correlation between Ea and pulmonary arterial elastance (PAC) were even more significant ( r=-0.888, P<0.001). Compared with Ea<0.555 group, Ea≥0.555 group presented with higher serum NT-proBNP values (4 443 (1 792, 8 554) ng/L vs. 1 721 (480, 4 528)ng/L, P<0.001), higher PVR (3.4 (2.5, 4.7) Wood vs. 1.4 (0.9, 2.2) Wood, P<0.001), lower cardiac output (3.0 (2.3, 3.9) L/min vs. 4.3 (3.8, 4.9) L/min, P<0.001), and lower PAC (1.6 (1.3, 2.0) ml/mmHg vs. 4.0 (3.0, 6.0) ml/mmHg, P<0.001). The median follow-up time was 392 (166, 811) days. The Kaplan-Meier survival curve demonstrated a lower event-free survival rate in the Ea≥0.555 group compared to the Ea<0.555 group ( Plog-rank<0.001). After multivariate adjustment, Ea ( HR=1.734, P<0.001) remained significantly associated with the primary outcome. Subgroup analysis indicated that Ea was associated with the primary outcome across all subgroups. The AUC was 0.724 ( P<0.001) for Ea to predict event-free survival calculated from ROC analysis. Conclusions:Ea is closely related to parameters reflective of right ventricular afterload. Increased Ea is an independent predictor of adverse outcomes in patients with HF.

Objective:To compare the mechanical properties between our self-designed axially controlled compression spinal rod (ACCSR) and conventional spinal rod (CSR) for lumbar spondylolysis (LS).Methods:This study selected 36 ACCSRs (the ACCSR group) and 36 CSRs (the CSR group), both of which were in a diameter of 6.0 mm and manufactured in the same batch. They were subjected respectively to biomechanical tests of spinal rod and pedicle screw-rod internal fixation system. In spinal rod tests: the stiffness and yield load of the spinal rods were calculated using four-point bending tests ( n=7) and comparisons were made between the 2 groups; spinal rod fatigue tests ( n=8) recorded the successful compression loads after 2.5 million cycles of loading and compared them with the maximum force at the isthmus of a normal adult's unilateral lumbar spine (198.72 N). In tests of the pedicle screw-rod internal fixation system, the axial compression tests ( n=7) measured the axial gripping capacity, the axial torsion tests ( n=7) the torsional gripping capacity, and the lateral compression tests ( n=7) the stiffness and yield load of pedicle screws in the 2 groups respectively. Results:The stiffness [(1,543.37±61.41) N/mm] and yield load [1,338.57 (1,282.00, 1,353.80) N] of ACCSR group were significantly smaller than those of CSR group [(3,797.63±156.15) N/mm and 4,059.95 (3,813.80, 4,090.89) N] ( P<0.05). The spinal rod fatigue tests showed that the respective loads of CSR and ACCSR passing the 2.5 million fatigue tests were 640.00 N and 320.00 N, both larger than the maximum force at the unilateral lumbar isthmus of a normal adult (198.72 N). There were no significant differences between the ACCSR group and the CSR group in the axial gripping capacity and torsional gripping capacity, as well as in stiffness and yield load of screws between the 2 groups ( P>0.05). Conclusions:In fixation of LS, although the yield load, stiffness and fatigue resistance of ACCSR are inferior to those of CSR, the biomechanical properties of the two sets of pedicle screw-rod internal fixation system are comparable. The fatigue resistance of ACCSR can meet the stress requirements of the normal human isthmus.

Objective To explore the key active ingredients and action characteristics of Wenxing Jingjintong Gel Patch in the treatment of rheumatoid arthritis(RA)based on the systematic pharmacology and LC-MS/MS technology.Methods The information of active ingredient from Wenxing Jingjintong Gel Patch was established through LC-MS/MS analysis and literature retrieval.The targets of the active ingredients were predicted using Swiss Target Prediction platform and then mapped with the RA-related targets obtained from GeneCards,DrugBank,and OMIM databases to identify the intersecting targets.The"active ingredients-effective targets"network was constructed through the Cytoscape software.The shared targets were imported into STRING database to construct a protein-protein interaction network.GO function and KEGG pathway enrichment analysis were performed using the Metascape database.Molecular docking studies were conducted using AutoDock software to investigate the interactions between key ingredients and target proteins.Results A total of 142 active ingredients were identified in Wenxing Jingjintong Gel Patch by wsing LC-MS/MS,which were further supplemented to 174 through literature retrieval.There were 175 shared targets between the active ingredients and RA.It was anticipated that Wenxing Jingjintong Gel Patch exerted immune regulation and anti-inflammatory and analgesic effects through the interaction between key active ingredients such as berberine,neobavaisoflavone,and palmatine chloride with key targets,including TNF,IL6,and AKT1 to regulate PI3K/Akt1,JAK/STAT,and MAPK signaling pathways.In 1 152 molecular docking validation,94%of them had binding energies less than-5.0 kcal·mol-1,while 51%of them had binding energies less than-7.0 kcal·mol-1.It was indicated that there was a good binding affinity between the potential active ingredients and core targets.Conclusion This study predicted the active ingredients and action characteristics of Wenxing Jingjintong Gel Patch in the treatment of RA,which provided a theoretical basis for further clinical application and quality control.

Objective To prepare a dissolvable microneedle(DMN)with a tip-layer loaded with hyaluronic acid(HA)modified sinomenine hydrochloride liposomes(HA-SMH-Lip),as well as characterize,evaluate its in vitro transdermal permeability,cellular uptake ability,and anti-inflammatory ability.Methods HA-SMH-Lip-DMNs were prepared by a two-step casting method,and the drug loading capacity was determined using HPLC.The morphology,skin permeation properties and in vitro transdermal ability were investigated by scanning electron microscopy,puncture assay and Franz diffusion cell method.Fluorescent microneedles were prepared by replacing HA-SMH-Lip with fluorescein isothiocyanate liposomes(HA-FITC-Lip/FITC-Lip).The uptake behavior of inflammation cells on HA-FITC-Lip-DMNs/FITC-Lip-DMNs was investigated using a flow cytometer and a fluorescence microscope.To evaluate the anti-inflammatory activity of HA-SMH-Lip-DMNs,the levels of inflammatory factors including nitric oxide(NO),tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β),and IL-10 in cell supernatants were measured using an ELISA kit.Results The prepared HA-SMH-Lip-DMNs have uniform shape and size,integral and visually pleasing array,and an average drug loading of(114.01±1.04)μg.Additionally,they have good puncture ability.The results of in vitro transdermal experiments showed that the accumulated amounts of HA-SMH-Lip-DMNs were(101.47±2.91)μg·cm-2 at 36 hours.Its transdermal ability was better than that of the SMH solution group and SMH liposome group.In vitro cellular uptake results indicated that HA-FITC-Lip-DMNs were more effectively taken up by RAW 264.7 cells(P＜0.01).Compared to the model group,HA-SMH-Lip-DMNs group significantly reduced TNF-α,IL-1β,and NO levels while increase IL-10 levels(P＜0.01).Conclusion The prepared HA-SMH-Lip-DMNs have a complete and beautiful morphology with excellent cellular uptake capability,remarkable in vitro transdermal performance,and potent anti-inflammatory properties.HA-SMH-Lip-DMNs are expected to become a new type of transdermal drug delivery system.

OBJECTIVE To investigate the effects of Compound troxerutin and poreine cerebroside injection on the activity of cytochrome P450 （CYP450） enzyme in vivo and in vitro. METHODS Human liver microsomes were incubated with Compound troxerutin and poreine cerebroside injection （volume fraction 0.05%-10%） and the specific probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6 and CYP3A4 for 30 min. The production of corresponding metabolites was detected by ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and the half inhibitory concentration （IC50） was calculated. The relative mRNA expression （i.e. induction multiple） of CYP450 enzyme was determined by real-time fluorescence quantitative PCR after human primary hepatocytes were incubated with Compound troxerutin and poreine cerebroside injection （volume fraction 0.05%-10%） or 3 positive inducers of CYP1A2， CYP2B6， CYP3A4 for 48 hours. Male SD rats were randomly divided into control group （normal saline+probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， CYP3A4 8， 2， 1， 1， 10， 10， 8 mg/kg） and experimental group （Compound troxerutin and poreine cerebroside injection 0.9 mL/kg+probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， CYP3A4 8， 2， 1， 1， 10，10， 8 mg/kg）， with 6 rats in each group. The pharmacokinetic parameters of probe substrates were detected by UPLC-MS/MS and Cocktail probe drug method. RESULTS After the lzqpharm@126.com treatment of 0.05%-10% Compound troxerutin and poreine cerebroside injection， the activities of CYP2B6， CYP2C8 and CYP2C19 in human liver microsomes had no significant change， and IC50 could not be fitted； IC50 of CYP1A2， CYP2C9， CYP2D6 and CYP3A4 were 419.90%， 97.78%， 176.00%， 19.42%， respectively. After the treatment of 0.05%-10% Compound troxerutin and poreine cerebroside injection， the average induction multiple of CYP3A4 mRNA in human primary hepatocytes （No. MHK） was 4.88 （and the average induction multiples of 2 concentration points were higher than 2）. After the treatment of Compound troxerutin and poreine cerebroside injection， AUC0－t and AUC0－∞ of CYP2C8， CYP2C9 and CYP2C19 substrates were increased significantly， CL of CYP2C8 and CYP2C19 substrates were decreased significantly， while t1/2 of CYP2C9 substrate was prolonged significantly （P＜0.05）. CONCLUSIONS Compound troxerutin and poreine cerebroside injection has no obvious inhibitory effect on CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6 and CYP3A4 in human liver microsomes in vitro， but can induce the mRNA expression of CYP3A4 in human primary hepatocytes in vitro， and can inhibit the activities of CYP2C8， CYP2C9 and CYP2C19 in rats in vivo.

Objective:To analyze the influencing factors and perform the prediction of olfactory disorders in patients with chronic rhinosinusitis（CRS） based on artificial intelligence. Methods:The data of 75 patients with CRS who underwent nasal endoscopic surgery from October 2021 to February 2023 in the Department of Otorhinolaryngology Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively. There were 53 males and 22 females enrolled in the study, with a median age of 42.0 years old. The CRS intelligent microscope interpretation system was used to calculate the proportion of area glands and blood vessels occupy in the pathological sections of each patient, and the absolute value and proportion of eosinophils, lymphocytes, plasma cells and neutrophils. The patients were grouped according to the results of the Sniffin' Sticks smell test, and the clinical baseline data, differences in nasal mucosal histopathological characteristics, laboratory test indicators and sinus CT were compared between the groups. Determine the independent influencing factors of olfactory disorders and receiver operating characteristic curves（ROC） were used to evaluate the performance of the prediction model. Statistical analysis was performed using SPSS 25.0 software. Results:Among the 75 CRS patients, 25 cases（33.3%） had normal olfaction and 50 cases（66.7%） had olfactory disorders. Multivariate Logistic regression analysis showed that tissue eosinophils percentage（OR=1.032, 95%CI 1.002-1.064, P=0.036）, Questionnaire of olfactory disorders-Negative statement（QOD-NS）（OR=1.079, 95%CI 1.004-1.160, P=0.040） and Anterior olfactory cleft score（AOCS）（OR=2.672, 95%CI 1.480-4.827, P=0.001） were independent risk factors for olfactory disorders in CRS patients. Further research found that the area under the ROC curve（AUC） of the combined prediction model established by the tissue eosinophil percentage, QOD-NS and AOCS was 0.836（95%CI 0.748-0.924, P<0.001）, which is better than the above single factor prediction model in predicting olfactory disorders in CRS. Conclusion:Based on pathological artificial intelligence, tissue eosinophil percentage, QOD-NS and AOCS are independent risk factors for olfactory disorders in CRS patients, and the combination of the three factors has a good predictive effect on CRS olfactory disorders.
Male ; Female ; Humans ; Adult ; Retrospective Studies ; Artificial Intelligence ; Rhinosinusitis ; Rhinitis/complications* ; Nasal Polyps/complications* ; Sinusitis/complications* ; Olfaction Disorders/etiology* ; Smell ; Chronic Disease

Objective:To summarize the research status and contents of the needs of breast cancer patients undergoing first operation.Methods:The articles related to the needs of patients undergoing first surgery for breast cancer were searched by computer in PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Database, VIP and China Biology Medicine disc. The search period was from January 1, 2013 to December 31, 2022.Results:A total of 17 articles were included, and the research design mainly focused on qualitative and observational studies. Breast cancer patients with first operation had a high degree of demand, and the demand content was diverse, mainly including information needs, health guidance needs, emotional needs and social support needs. The needs of breast cancer patients with different ages and different treatment stages were different.Conclusions:It is suggested that a personalized needs intervention plan should be formulated to meet the diversified needs of breast cancer patients.

Objective:To investigate the prognostic value and related factors of heart-type fatty acid binding protein (H-FABP) in patients with heart failure.Methods:A total of 877 consecutive patients who were admitted to heart failure care unit of Fuwai hospital and diagnosed as heart failure from July 2015 to July 2017 were enrolled in this study. Baseline serum H-FABP concentration was measured by fluorescence lateral flow immunoassay. According to serum H-FABP levels, patients were divided into three groups: low H-FABP group (H-FABP≤4.04 ng/ml, n=292), middle H-FABP group (H-FABP 4.04-7.02 ng/ml, n=292) and high H-FABP group (H-FABP≥7.02 ng/ml, n=293). The general clinical characteristics were collected and compared among the three groups. According to whether heart failure was caused by coronary artery disease or not, patients with heart failure were divided into ischemic heart failure and non-ischemic heart failure. Multivariate linear regression analysis was performed to explore the independent risk factors of H-FABP. The primary endpoint events were the composite of all-cause death or heart transplantation. Multivariate Cox regression analyses, receiver operating characteristic (ROC) curves, risk prediction tests with multivariate Cox regression model and Kaplan-Meier analyses were conducted to investigate the relationship between H-FABP and the prognosis of heart failure. Results:Multivariate linear regression analysis showed that age, coronary artery disease, alanine aminotransferase, uric acid and N-terminal pro-B type natriuretic peptide (NT-proBNP) were positively associated with H-FABP (β=0.012, 0.238, 0.001, 0.345 and 0.063 respectively,all P<0.05), while female, hemoglobin, albumin, sodium, and estimated glomerular filtration rate (eGFR) were negatively associated with H-FABP (β=-0.184, -0.006, -0.016, -0.034 and -0.006 respectively, all P<0.05). One hundred and nineteen patients (13.6%) lost to follow-up, and 246 patients (32.5%) suffered from all-cause death or heart transplantation during the median follow-up duration of 931 (412-1 185) days. Multivariate Cox regression analysis showed that baseline H-FABP (log 2H-FABP) level was the independent predictor of all-cause death or heart transplantation in patients with heart failure ( HR=1.39, P<0.001). ROC curves showed that baseline H-FABP was a predictor of all-cause death or heart transplantation in patients with heart failure within 3 months, 1 year and 2 years (areas under the curves were 0.69, 0.69 and 0.71 respectively), and the best cut-off values were 5.85 ng/ml, 6.54 ng/ml and 6.54 ng/ml respectively. Risk prediction test with multivariate Cox regression model showed that baseline H-FABP could provide additional prognostic value in predicting all-cause death or heart transplantation for patients with heart failure on top of basic model and baseline NT-proBNP ( P<0.001). Taking 6.54 ng/ml and trisected levels of H-FABP as cut-off values respectively, Kaplan-Meier analyses showed that the survival rates were significantly different among the two or three groups ( P<0.001). Subgroup analyses showed that baseline H-FABP (log 2H-FABP) level was an independent predictor of all-cause death or heart transplantation in patients with ischemic heart failure ( HR=1.74, P<0.001), as well as in patients with non-ischemic heart failure ( HR=1.28, P=0.027). Conclusions:Age, sex, coronary artery disease, hemoglobin, albumin, alanine aminotransferase, sodium, eGFR, uric acid and NT-proBNP are associated with H-FABP level. Baseline H-FABP level is an independent predictor of all-cause death or heart transplantation in patients with heart failure. On top of basic model and baseline NT-proBNP, baseline H-FABP could provide additional prognostic value in predicting adverse events for patients with heart failure.