OBJECTIVE To investigate the clinical efficacy of integrating pharmacists into family health teams （FHTs） for long-term medication therapeutical management （MTM） in stroke patients， and empirically evaluate the service model. METHODS A pharmacist team， jointly established by clinical and community pharmacists from the Affiliated Suzhou Hospital of Nanjing Medical University （hereinafter referred to as “our hospital”）， developed a pharmacist-supported MTM model integrated into FHTs. Using a prospective randomized controlled design， 170 stroke patients discharged from our hospital （July 2022-December 2023） and enrolled in FHTs at Suzhou Runda Community Hospital were randomly divided into trial group （88 cases） and control group （82 cases） according to random number table. The control group received routine FHTs care （without pharmacist involvement in the team collaboration）， while the trial group xhz8405@126.com received 12-month MTM services supported by pharmacists via an information platform. These services specifically included innovative interventions such as personalized medication regimen optimization based on the MTM framework， dynamic medication adherence management， medication safety monitoring， a home medication assessment system， and distinctive service offerings. Outcomes of the 2 grousp were compared before and after intervention， involving medication adherence （adherence rate， adherence score）， compliance rates for stroke recurrence risk factors [blood pressure， low-density lipoprotein cholesterol （LDL-C）]， and incidence of adverse drug reactions （ADR）. RESULTS After 12 months， the trial group exhibited significantly higher medication adherence rates， improved adherence scores， higher compliance rates for blood pressure and LDL-C targets compared to the control group （P＜0.05）. The incidence of ADR in the trial group （4.55%） was significantly lower than that in the control group （8.11%）， though the difference was not statistically significant （P＞ 0.05）. CONCLUSIONS Pharmacist involvement in FHTs to deliver MTM services significantly enhances medication adherence and optimizes risk factor for stroke recurrence， offering practical evidence for advancing pharmaceutical care in chronic disease management under the family doctor system.

Objective:To discuss the clinical efficacy of recombinant human growth hormone(rhGH)in the treatment of the pediatric patients with growth hormone deficiency(GHD)and idiopathic short stature(ISS),and to clarify its clinical application value in the pediatric patients with short stature of different etiologies.Methods:The clinical data of 132 children with short stature who treated with rhGH from January 2018 to January 2023 were collected.They were divided into GHD group(n=70)and ISS group(n=62)based on different etiologies.The bone age,target height(TH),body mass index(BMI),height standard deviation score(HtSDS),changes in height standard deviation scores(ΔHtSDS)before treatment and 6 months after treatment,and growth velocity(GV)of the pediatric patients were calculated.Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were used to balance the confounding factors between the pediatric patients in two groups and the efficacy and safety of the pediatric patients in two groups were evaluated.Results:There were significant differences in whether children were full-term,bone age,bone age maturity,and TH of the pediatric patients between two groups(P<0.05).Compared with before treatment,the height and HtSDS of the pediatric patients in both GHD and ISS groups were significantly increased after treated for 6 months(P<0.05).Before matched by PSM,there were significant differences in full-term,bone age,bone age maturity,and TH of the pediatric patients between two groups(P<0.05).After matched by PSM,there were no significant differences in gender,region,term birth status,mode of delivery,feeding method,age,bone age,height,BMI,TH,and pretreatment HtSDS of the pediatric patients between two groups(P>0.05);the standardized mean difference(SMD)differences of covariates except for region were<0.2.After weighted by IPTW,there were no significant differences in gender,region,term birth status,mode of delivery,feeding method,age,bone age,height,BMI,TH,and pretreatment HtSDS of the pediatric patients between two groups(P>0.05);all SMD of covariates except for term birth status were<0.2.Before balancing covariates,after meatched by PSM matching,and after weighted by IPTW weighting compared with GHD group,the GV and ΔHtSDS of the pediatric patients in ISS group were slightly increased,but the difference was not significant(P>0.05).In terms of adverse reactions,2 cases(2.68%)of fasting hyperglycemia and 7 cases(10.00%)of hypothyroidism occurred in GHD group;3 cases(4.84%)of fasting hyperglycemia and 2 cases(3.23%)of hypothyroidism occurred in ISS group.Conclusion:rhGH can promote the height increase in the patients with GHD and ISS,and there is no significant difference in the height-increasing efficacy between GHD and ISS children.The incidence of adverse reactions is relatively low during treatment,indicating good overall safety.

Objective To compare the cost and utility of aflibercept and ranibizumab in the treatment of diabetic macular edema(DME),in order to provide a reference for the selection of treatment regimens from the perspective of pharmacoeconomics.Methods The Markov model was established by extracting the clinical medication patterns,the survival status of the two treatment regimens within 10 years were simulated,the cost and health utilities were calculated respectively,and the incremental cost-utility ratio(ICUR)was obtained.Compared with the 2022 per capita gross domestic product(GDP)of China,which was 1 time,as the willingness to pay(WTP),the cost-utility advantage scheme was selected.Results During the simulation period,the ICUR of aflibercept compared with ranibizumab was 61 024.22 yuan/quality-adjusted life year(QALY),which was lower than that of WTP,which had obvious economic benefits.Univariate sensitivity analysis showed that the metastasis probability of visual acuity improvement with aflibercept and the number of ranibizumab injections per year were important influencing factors for ICUR.Probabilistic sensitivity analysis showed that when WTP was 1 time of the GDP,aflibercept had a significant cost-utility advantage,the economic probability was 63.7%,and the results were relatively stable.Conclusion For the treatment of DME,aflibercept has a cost-utility advantage over ranibizumab.

Interstitial lung disease is a common lung disease of connective tissue disease,which seriously affects the survival rate and quality of life of patients with connective tissue disease.Interstitial lung disease may occur in the whole course of connective tissue disease.Therefore,imaging plays an important role in the whole disease cycle of connective tissue-associated interstitial lung disease.At present,high-resolution computed tomography is the cornerstone of screening,diagnosis and follow-up of connective tissue-associated interstitial lung disease,but ionizing radiation is a potential limiting factor in its clinical application.In recent years,new imaging techniques have developed rapidly,and some promising research results have been achieved in the early screening,diagnosis and efficacy evaluation of connective tissue-associated interstitial lung disease,and they are gradually moving towards non-invasive,low-radiation and accurate imaging analysis techniques.This article reviews the advances in imaging research of connective tissue-associated interstitial lung disease,and analyzes the advantages and disadvantages of various new imaging techniques,as well as the challenges and prospects.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Apoptosis ; Signal Transduction ; Nasopharyngeal Neoplasms/pathology*

Objective:To investigate the current status of prevention and treatment of esophagogastric variceal bleeding (EVB) in cirrhotic portal hypertension patients in Ningxia region.Methods:The retrospective and descriptive study was conducted. The clinical data of 820 cirrhotic portal hypertension patients who were admitted to 21 medical centers in Niangxia region from January 2018 to December 2020 were collected, including 85 cases in Ningxia Hui Autonomous Region People′s Hospital, 73 cases in the Fifth People′s Hospital of Ningxia Hui Autonomous Region, 59 cases in the Wuzhong People′s Hospital, 52 cases in the Qingtongxia People′s Hospital, 50 cases in the Guyuan People′s Hospital, 47 cases in the Yuanzhou District People′s Hospital of Guyuan City, 47 cases in the Yinchuan Second People′s Hospital, 40 cases in the General Hospital of Ningxia Medical University, 40 cases in the Tongxin People′s Hospital, 35 cases in the Yinchuan First People′s Hospital, 34 cases in the Third People′s Hospital of Ningxia Hui Autonomous Region, 32 cases in the Zhongwei People′s Hospital, 30 cases in the Lingwu People′s Hospital, 30 cases in the Wuzhong New District Hospital, 30 cases in the Yanchi People′s Hospital, 29 cases in the Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, 28 cases in the Shizuishan Second People′s Hospital, 25 cases in the Shizuishan First People′s Hospital, 21 cases in the Haiyuan People′s Hospital, 20 cases in the Pengyang People′s Hospital, 13 cases in the Longde People′s Hospital. There were 538 males and 282 females, aged (56±13)years. Observation indicators: (1) clinical charac-teristics of cirrhotic portal hypertension patients; (2) overall prevention and treatment of EVB in cirrhotic portal hypertension patients; (3) prevention and treatment of EVB in cirrhotic portal hypertension patients from different grade hospitals. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Results:(1) Clinical characteristics of cirrhotic portal hypertension patients: of 820 cirrhotic portal hypertension patients, 271 cases were in compensated stage and 549 cases were in decompensated stage. Of the 271 cases in compensated stage, there were 183 maels and 88 females, aged (53±12)years. There were 185 Han people, 85 Hui people and 1 case of other ethic group. The etiological data of liver cirrhosis showed 211 cases of viral hepatitis B, 4 cases of alcoholic liver disease, 8 cases of viral hepatitis C, and 48 cases of other etiology. There were 235 cases of Child-Pugh grade A and 36 cases lack of data. Of the 549 cases in decompensated stage, there were 355 males and 194 females, aged (57±14) years. There were 373 Han people, 174 Hui people and 2 cases of other ethic group. The etiological data of liver cirrhosis showed 392 cases of viral hepatitis B, 33 cases of alcoholic liver disease, 10 cases of viral hepatitis C, and 114 cases of other etiology. There were 80 cases of Child-Pugh grade A, 289 cases of grade B, 170 cases of grade C and 10 cases lack of data. (2) Overall prevention and treatment of EVB in cirrhotic portal hypertension patients: of 271 patients in compensated stage, 38 cases received non-selective β-blocker (NSBB) therapy, 16 cases received endoscopic treatment, 6 cases received interventional therapy. Of 549 patients in decompensated stage, 68 cases received NSBB therapy, 46 cases received endoscopic treatment, 28 cases received interventional therapy. (3) Prevention and treatment of EVB in cirrhotic portal hypertension patients from different grade hospitals: of 271 patients in compensated stage, 181 cases came from tertiary hospitals, of which 28 cases received NSBB therapy, 15 cases received endoscopic treatment, 6 cases received interventional therapy. Ninety cases came from secondary hospitals, of which 10 cases received NSBB therapy, 1 cases received endoscopic treatment. There was no significant difference in NSBB for prevention of EVB between tertiary and secondary hospitals ( χ2=0.947, P>0.05), while there was a significant difference in endoscopic treatment for prevention of EVB between tertiary and secondary hospitals ( χ2=5.572, P<0.05). Of 549 patients in decompensated stage, 309 cases came from tertiary hospitals, of which 22 cases received NSBB therapy, 29 cases received endoscopic treatment, 22 cases received interventional therapy. Two hundreds and fourty cases came from secondary hospitals, of which 46 cases received NSBB therapy, 17 cases received endoscopic treatment, 6 cases received interven-tional therapy. There were significant differences in NSBB and interventional therapy for prevention of EVB between tertiary and secondary hospitals ( χ2=18.065, 5.956, P<0.05). Conclusions:The proportion of receiving EUB prevention in cirrhotic portal hypertension in Ningxia is relatively low. For patients with compensated liver cirrhosis, the proportion of NSBB therapy and endoscopic treatment in the secondary hospitals was lower than that in tertiary hospitals. For patients with decompensated liver cirrhosis, the proportion of interventional treatment in secondary hospitals is lower than that of tertiary hospitals, but the proportion of NSBB in secondary hospitals taking is higher than that of tertiary hospitals.

Objective: To explore the Expressions of multiple inflammation markers in the patients with 2019 novel coronavirus pneumonia (COVID-19) and their clinical values, and to provide theoretical basis for clinical diagnosis and treatment. Methods: A total of 164 patients, diagnosed with COVID-19 and admitted to Guangzhou Eighth People's Hospital from January to February 2020, were selected as the research group and divided into three groups (ordinary, severe, and critically severe pneumonia) according to the disease severity. Meandwhile 66 non-infected patients during the same period were selected as negative control group. The expressions of WBC, LYM, CRP, SAA, and PCT were retrospective studied and compared between groups. The diagnostic values of WBC, CRP, SAA and the combination of these three markers in all patients with COVID-19 and in different severity groups were analyzed by ROC curve. Results: Compared with control group (WBC count :8.13(6.51,9.42)×10⁹/L, LYM count:2.00(1.28,2.43)×10⁹/L), WBC count [4.94(4.05, 6.67) ×10⁹/L] and LYM count [1.33(0.94, 1.96) ×10⁹/L] of COVID-19 patients were significantly reduced (Z=-7.435, P<0.01; Z=-4.906, P<0.01) . Compared with the control group [CRP: 1.36 (0.57~5.67) mg/ml; SAA:[4.98 (4.80~15.75) mg/mL], CRP [7.93 (2.45~23.98) mg/ml] and SAA [34.13 (4.83~198.40) mg/ml] were increased in research group (Z=-5.72, P<0.01; Z=-4.166, P<0.01) . PCT in the control group and the research group were 0.100 0(0.030 6~0.100 0)ng/ml and 0.044 5(0.031 6~0.077 0)ng/ml, respectively. There was no statistical difference between two groups (Z=-1.451, P=0.147) . The areas under the ROC curve (AUC) of WBC, CRP and SAA in patients with COVID-19 were 0.814, 0.742, 0.673, respectively (P<0.01), while the AUC of the combination of three indexes for COVID-19 diagnosis was 0.882, with 83.33%(55/66) specificity and 84.76% (139/164) sensitivity, P<0.01.The AUCs of WBC, CRP, and SAA for predicting severe and critically severe COVID-19 were 0.799, 0.779, and 0.886 , respectively (P<0.01), and the AUC of the combination of three indexes for the diagnosis of severe and critically severe COVID-19 was 0.924, with 78.67% (118/150) specificity and 14/14 sensitivity (P<0.01). Conclusion Combining detection of WBC, CRP and SAA can improve the specificity and sensitivity of COVID-19 diagnosis, with a high diagnostic value for severe and critically severe COVID-19.

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

Objective:To estimate the predictive performance of the population pharmacokinetics software JPKD-vancomycin on predicting the vancomycin steady-state trough concentration, and to analyze the related factors affecting the predictive performance.Methods:The clinical data of patients who were treated with vancomycin and received therapeutic drug monitoring (TDM) admitted to Suzhou Hospital Affiliated to Nanjing Medical University from July 2013 to December 2018 were enrolled. All patients were designed an empirical vancomycin regimen (initial regimen) according to vancomycin medication guidelines. Steady-state trough concentrations of vancomycin were determined at 48 hours after the first dose and 0.5 hour before the next dose. Dosage regimen was adjusted when steady-state trough concentration was not in 10-20 mg/L (adjustment regimen), and then the steady-state trough concentration was determined again 48 hours after adjustment. First, the JPKD-vancomycin software was used to calculate the initial regimen and predict the steady-state trough concentration according to the results calculated by classic pharmacokinetic software Vancomycin Calculator. Second, the JPKD-vancomycin software was used to adjust the vancomycin dosage regime and predict the steady-state trough concentration of adjustment regimen. The weight residual (WRES) between the predicted steady-state trough concentration (C pre) and the measured steady-state trough concentration (C real) was used to evaluate the ability of the JPKD-vancomycin software for predicting the vancomycin steady-state trough concentration. The TDM results of initial regimen were divided into accurate prediction group (WRES < 30%) and the inaccurate prediction group (WRES ≥ 30%) according to the WRES value. Patient and disease characteristics including gender, age, weight, height, the length of hospital stay, comorbidities, vasoactive agent, mechanical ventilation, smoking history, postoperative, obstetric patients, trauma, laboratory indicators, vancomycin therapy and TDM results were collected from electronic medical records. Univariate and multivariate Logistic regression analysis was used to screen the related factors that influence the predictive performance of JPKD-vancomycin software, and the receiver operating characteristic (ROC) curve was drawn to evaluate its predictive value. Results:A total of 310 patients were enrolled, and 467 steady-state trough concentrations of vancomycin were collected, including 310 concentrations of initial regimen and 157 concentrations of adjustment regimen. Compared with the initial regimen, the WRES of adjusted regimen was significantly reduced [14.84 (6.05, 22.89)% vs. 20.41 (11.06, 45.76)%, P < 0.01], and the proportion of WRES < 30% increased significantly [82.80% (130/157) vs. 63.87% (198/310), P < 0.01]. These results indicated that JPKD-vancomycin software had a better accuracy prediction for steady-state trough concentration of the adjusted regimen than the initial regimen. There were 198 concentrations in the accurate prediction group and 112 in the inaccurate prediction group. Univariate Logistic regression analysis showed that women [odds ratio ( OR) = 0.466, 95% confidence interval (95% CI) was 0.290-0.746, P = 0.002], low body weight ( OR = 0.974, 95% CI was 0.953-0.996, P = 0.022), short height ( OR = 0.963, 95% CI was 0.935-0.992, P = 0.014), low vancomycin clearance (CL Van; OR < 0.001, 95% CI was 0.000-0.231, P = 0.023) and postoperative patients ( OR = 1.695, 95% CI was 1.063-2.702, P = 0.027) were related factors affecting the predictive performance of JPKD-vancomycin software. Multivariate Logistic regression analysis indicated that women ( OR = 0.449, 95% CI was 0.205-0.986, P = 0.046), low CL Van ( OR < 0.001, 95% CI was 0.000-0.081, P = 0.015) and postoperative patients ( OR = 2.493, 95% CI was 1.455-4.272, P = 0.001) were independent risk factors for inaccurate prediction of JPKD-vancomycin software. The ROC analysis indicated that the area under ROC curve (AUC) of the CL Van for evaluating the accuracy of JPKD-vancomycin software in predicting vancomycin steady-state trough concentration was 0.571, the sensitivity was 56.3%, and the specificity was 57.1%. The predictive performance of JPKD-vancomycin software was decreased when CL Van was lower than 0.065 L·h -1·kg -1. Conclusions:JPKD-vancomycin software had a better predictive performance for the vancomycin steady-state trough concentrations of adjustment regimen than initial regimen. JPKD-vancomycin software had a poor predictive performance when the patient was female, having low CL Van, and was postoperative. The predictive performance of JPKD-vancomycin software was decreased when CL Van was lower than 0.065 L·h -1·kg -1.