After entering the body from the drug delivery site, antitumor nanomedicines need to cross a series of physiopathological barriers to reach the target site of action to effectively exert antitumor therapeutic effects. The ligand modification strategy is a classic method to enhance the efficiency of nanomedicine delivery in vivo, but the contradiction between the single ligand modification strategy, which is characterized by unity and stage, and the in vivo delivery process, which is characterized by versatility and whole-process characteristics, determines that nanomedicines modified by a single ligand alone cannot satisfy the target efficacy requirements. Therefore, the use of multiligand combinatorial modification strategies by virtue of nanomedicine surface area advantages is key to advancing the next generation of smart nanomedicines. In this paper, on the basis of summarizing and classifying the commonly used functional ligands for in vivo delivery, the advantages and research progress of multiligand combination modification of antitumor nanomedicines are discussed with special focus, and the multiligand combination modification is classified as synergistic and complementary according to the combination of the ligands, which is of great significance to ensure that antitumor nanomedicines can overcome the multiple physiopathological barriers to achieve precise delivery.

Objective To utilize bioinformatic approaches to elucidate the correlation between secreted phosphoprotein 1(SPP1)and immune infiltration in various malignancies,elucidating the mechanism of gene function in cancer-immune cell interplay.Methods Cancer samples were derived from the Cancer Genome Atlas(TCGA)and Genotype-tissue Expression(GTEx)database,examining SPP1 expression difference between tumors and normal tissues using Gene Expression Profiling Interactive Analysis(GEPIA2),and its correlation with different immune cells in extracellular matrix via TIMER2 Database.SPP1's association with interacting molecules was scrutinized on the STRING website,followed by assessment of its distinct functional state across various cancers from Cancer Single-cell State Atlas Database(Cancer SEA).Results In 32 tumor types,SPP1 mRNA is significantly elevated in 23 types of cancers and correlates heavily with fibroblast,integrin family,and CD44.Furthermore,the SPP1 gene exhibits profound specificity in tumor functions such as vascular invasion,metastasis,DNA damage,and repair.Conclusion Specific expression of SPP1 in tumors signifies a significant correlation with tumor immune cells in the extracellular matrix,promoting tumor progression and invasion.This suggests that targeted monitoring of SPP1 could serve as a prospective cancer diagnostics/therapeutics biomarker.

In order to standardize the clinical diagnosis and treatment of upper airway cough syndrome (UACS) for children in China, Dongzhimen Hospital of Beijing University of Chinese Medicine and Affiliated Hospital of Liaoning University of Traditional Chinese Medicine initiated the development of this Traditional Chinese Medicine Diagnosis and Treatment Guidelines for Children with Upper Airway cough Syndrome based on evidence-based medical evidence. This guideline will process registration, write a plan, and develop relevant processes and writing norms, develop and publish official documents. This plan mainly introduces the scope of the guidelines, the purpose and significance, the composition of the guidelines working group, the management of conflicts of interest, the collection, selection and determination of clinical problems, the retrieval, screening and rating of evidence, and the consensus of recommendations. Registration information: This study has been registered in the international practice guidelines registry platform with the registration code of PREPARE-2023CN087.

Objective To investigate the prognosis of patients with hepatitis B virus(HBV)-related intrahepatic cholangiocarcinoma(ICC)whose HBV DNA was negative before surgical.Methods A retrospective analysis was conducted on the clinical data of 97 ICC patients who underwent surgery resection at the Fifth Medical Center of Chinese PLA General Hospital between October 2010 and January 2017.All patients were divided into HBV-related ICC(HBV-ICC)group(n=62)and non-HBV-related ICC(Con-ICC)group(n=35).HBV-ICC group included 34 patients with HBV core antigen positive(HBcAb+)and HBV surface antigen positive(HBsAg+),and 28 patients with HBcAb positive and HBsAg negative.Kaplan-Meier analysis was used to plot survival curves and compare the overall survival(OS)and postoperative recurrence-free survival(RFS)among patients in Con-ICC,ICC patients with HBsAg+/HBcAb+,and ICC patients with HBsAg-/HBcAb+.Univariate and multivariate Cox proportional hazard models were used to analyze independent influencing factor for OS,RFS and early postoperative recurrence among gender,age,pathogenic factor,liver cirrhosis,Child-Pugh grade,carbohydrate antigen 19-9(CA199),alpha-fetoprotein(AFP),glutamine transferase(GGT),alkaline phosphatase(ALP),total bilirubin(TBil),direct bilirubin(DBil),American Joint Committee on Cancer(AJCC)stage,tumor size,tumor number,tumor differentiation,microvascular invasion,lymph node metastasis,hepatectomy procedure,cholecystectomy,and follow-up treatment.Results Of the 97 patients,the median age was 56 years,and 79(81.4%)of them were male.The median follow-up time was 92.2 months.Eighty-eight(90.7%)patients presented with tumor recurrence and 73(75.3%)died.In multivariate analyses,HBV-ICC and CA199>37 kU/L were independent predictors of OS(HR=0.45,95%CI 0.26-0.77,P=0.003;HR=2.10,95%CI 1.24-3.57,P=0.006),RFS(HR=0.43,95%CI 0.27-0.68,P<0.001;HR=1.78,95%CI 1.12-2.81,P=0.014),and postoperative early recurrence(HR=0.42,95%CI 0.26-0.70,P=0.001;HR=2.02,95%CI 1.20-3.39,P=0.008).AJCC stage Ⅲ was an independent risk factor for postoperative RFS(HR=1.81,95%CI 1.04-3.14,P=0.037).Multiple tumor lesions was an independent risk factor for postoperative RFS and early recurrence(HR=1.73,95%CI 1.07-2.77,P=0.024;HR=1.90,95%CI 1.12-3.24,P=0.017).There was no statistically significant difference in OS,RFS,and early recurrence between HBV-ICC patients with HBsAg-/HBcAb+and Con-ICC patients(P<0.05),whereas HBsAg+/HBcAb+was a significant factor affecting postoperative OS(HR=0.32,95%CI 0.16-0.62,P=0.001),RFS(HR=0.32,95%CI 0.18-0.55,P<0.001),and early recurrence(HR=0.29,95%CI 0.15-0.54,P<0.001)in ICC patients.Conclusions The prognosis of HBV-ICC patients with preoperative HBV-DNA-is better than that of Con-ICC patients.The prognosis of HBV-ICC patients with HBcAb+/HBsAg-is worse than that of HBV-ICC patients with HBcAb+/HBsAg+,but similar to Con-ICC patients.Therefore,the postoperative stratified management of HBV-ICC patients should be emphasized.

Objective To investigate the biocompatibility of new gadolinium-doped hydroxyapatite(Gd-HA)composite scaffolds and to explore their feasibility as cell culture materials and bone tissue engineering scaffolds.Methods The Gd-HA composite scaffolds were chemically synthesized and placed under the electron microscope for observation.The experiment was divided into three groups,the HA group,the Gd-HA group,and the control group.Rabbit adipose-derived mesenchymal stem cells(ADSCs)were isolated,cultured and characterized,and the Gd-HA composite scaffold extract was added to the ADSCs in vitro culture system.Cell survival and cytotoxicity were assessed by live-dead cell staining,cell proliferation ability within the scaffolds was assessed by CCK-8 assay,and the scaffolds were assessed by alizarin red staining for cell osteogenic differentiation.The toxic reactions of the scaffold materials were observed by skin irritation test,systemic acute toxicity test and muscle tissue and liver and kidney pathology at the site of intramuscular implantation of the scaffolds.Results The Gd-HA composite scaffold showed irregular void structure under electron microscope.Cell morphology observation showed that ADSCs grew adherently to the wall and were long shuttle-shaped.The positivity rate of CD29 was 96.94％,CD44 was 97.90％,CD45 was 0.10％,and CD34 was 0.46％,which was obtained using flow cytometry.Live-dead cell staining showed that the amount of live cells in the Gd-HA group was significantly better than that in the hydroxyapatite(HA)group after 5 days of co-culture.CCK-8 assay showed no significant difference in cell proliferation within 0-3 days.After 3 days,the Gd-HA group was significantly better than the HA group and the control group(P＜0.05).Calcium nodule deposition after alizarin red staining was significantly better in the Gd-HA group than in the HA and control groups,showing a deeper red color.No skin irritation was observed in gross and skin tissue HE observations after the contact of the extract with the skin.The general condition of the experimental groups was good after the infusion of the extract into the abdominal cavity,and the body mass tended to increase steadily(P＞0.05).HE staining showed that inflammatory reaction at the interface between the material and muscle tissue of the stent intramuscular implantation site in Gd-HA group was significantly higher than that of the control group,and the inflammatory cell infiltration was gradually reduced with the prolongation of implantation time.At the 8th weeks the morphology of the tissue around the material was close to normal muscle tissue,and no pathological changes were observed in the HE staining of liver and kidney at the 12th week.Conclusion Gd-HA composite scaffolds exhibit good biocompatibility and facilitate cell proliferation and osteogenic differentiation,and they are expected to serve as good carriers for stem cell transplantation in tissue engineering.

Objective To investigate disease characteristics and hospitalization costs of children with Mycoplasma Pneumoniae pneumonia(MPP)admitted to Shanghai municipal medical hospitals from 2019 to 2023.Methods Depending on the Shanghai Municipal Hospital Pediatric Alliance,we retrospectively investigated community acquired MPP pediatric patients hospitalized in 22 municipal hospitals with pediatric qualifications(including 4 children's hospitals)in Shanghai from Jan 2019 to Dec 2023.We collected the patients'diagnosis codes,gender,age,length of hospital stay,hospitalization costs,and whether they progressed to severe Mycoplasma pneumoniae pneumonia(SMPP).Results From 2019 to 2023,a total of 29 045 hospitalized children with MPP were treated,with 6 035 cases(20.8%)identified as SMPP in the 22 hospitals.Trend analysis revealed a rising trend with years in the proportion of SMPP patients(χ2trend=365.498,P<0.001).Among the 4 children's hospitals,there were 18 710 cases with MPP,including 4 078 cases(21.8%)of SMPP.The proportion of SMPP patients also showed an increasing trend with years(χ2trend=14.548,P<0.001),and the proportion in 2023(23.0%)was higher than that in previous years with statistical significance.There were statistical differences in the seasonal distribution of MPP cases between different years,with higher proportions in summer and autumn overall.The age distribution of hospitalized MPP children varied among different years,with school-age children accounting for the majority(56.8%)in 2023.There was no difference in the distribution of severe cases between different genders,but there were differences in the proportion of severe cases among different age groups in different years,with a gradual increase in severe cases among children aged 1 to 3 years(χ2trend=191.567,P<0.001).The average length of hospital stay for MPP during the epidemic was higher than that during non-epidemic periods,and there were statistically significant differences in the average length of hospital stay between different years(P<0.001).The individual hospitalization costs during the epidemic were higher than in other years,and there were statistically significant differences in individual hospitalization costs between different years(P<0.001).The total hospitalization costs were still higher in 2019 and 2023.The individual hospitalization costs for SMPP were higher than for non-SMPP cases.Conclusion MPP outbreaks occurred in Shanghai in 2019 and 2023,with the higher proportions in summer and autumn overall.Compared to previous years,the number of hospitalized MPP children in Shanghai was higher in 2023,with a higher proportion of SMPP cases,especially among children under 3 years old.The individual per capita hospitalization expenses for SMPP cases were higher than for non-SMPP cases.

AIM:To investigate the alleviating effect of ethyl acetate extract from Platycladus orientalis leaves(EAEPOL)on diabetic cardiomyopathy(DCM)and its mechanisms.METHODS:Healthy adult C57BL/6 mice were ran-domly divided into normal control group,DCM group,and EAEPOL group.Cardiac structure and function of the mice were assessed by echocardiography.Myocardial fibrosis was evaluated though myocardial hydroxyproline content determi-nation,myocardial Masson and Sirius red staining,and collagen type I(Col I)and collagen type Ⅲ(Col Ⅲ)immunohis-tochemistry.The degree of myocardial oxidative stress was assessed by measuring malondialdehyde(MDA),superoxide dismutase(SOD)and total antioxidative capacity(T-AOC)levels using kits,as well as detection of nuclear factor E2-re-lated factor-2(Nrf-2)and heme oxygenase-1(HO-1)expression by qRT-PCR and Western blot.Endothelial-mesenchy-mal transition(EndMT)was evaluated by detecting CD31 and α-smooth muscle actin(α-SMA)protein expression by Western blot,and cadherin 5(CDH5)and fibroblast specific protein 1(FSP1)mRNA expression by qRT-PCR,as well as α-SMA immunofluorescence staining.RESULTS:(1)Mouse echocardiography revealed that compared with normal control group,heart rate(HR)and ejection fraction(EF)were significantly reduced in DCM group(P<0.05 or P<0.01),while left ventricular anterior wall thickness at systole and diastole(LVAWs and LVAWd)and left ventricular pos-terior wall thickness at systole and diastole(LVPWs and LVPWd)were significantly increased(P<0.05).Compared with DCM group,the mice in EAEPOL group showed significant increases in HR and EF(P<0.01),and marked decreases in LVAWs,LVAWd,LVPWs and LVPWd(P<0.05).(2)Compared with normal control group,the content of hydroxypro-line in mouse myocardium,the collagen area ratio shown by Sirius red and Masson staining,and the immunohistochemical positive area ratio of Col I and Col Ⅲ in DCM group were significantly increased(P<0.01).Compared with DCM group,the above myocardial fibrosis indicators in EAEPOL group were significantly reduced(P<0.05 or P<0.01).(3)Com-pared with normal control group,the myocardial MDA content and the expression of Nrf-2 in DCM group were significantly increased,while the SOD activity,the T-AOC and the expression of HO-1 was significantly decreased(P<0.01).Com-pared with DCM group,the myocardial MDA content in EAEPOL group was significantly reduced,while the SOD activity,the T-AOC,and the HO-1 and Nrf-2 expression were significantly enhanced(P<0.05 or P<0.01).(4)Compared with normal control group,the myocardial expression of CD31 and CDH5 in DCM group was significantly reduced,the expres-sion of α-SMA and FSP1 was significantly enhanced(P<0.05 or P<0.01),and the α-SMA positive area ratio by immuno-fluorescence staining was also increased(P<0.01).Compared with DCM group,EAEPOL significantly up-regulated the expression of CD31 and CDH5 and down-regulated the expression of α-SMA and FSP1,and the α-SMA positive area ratio by immunofluorescence staining was evidently decreased(P<0.05 or P<0.01).CONCLUSION:EAEPOL may attenuate myocardial fibrosis and improve cardiac function in DCM mice by suppressing oxidative stress and alleviating EndMT.

Objective To investigate clinical effect of tendons pulling,poking and kneading for the treatment of external humeral epicondylitis.Metods From January 2018 to December 2021,a multicenter randomized controlled study was per-formed to collect 192 patients with external humeral epicondylitis in Wangjing Hospital,Beijing Dianli Hospital,and Beijing Fengsheng Osteotraumatology Hospital,respectively,and they were divided into treatment group and control group by random number table method.There were 96 patients in treatment group,including 36 males and 60 females,aged from 28 to 60 years old with an average of(41.20±5.50)years old;the course of disease ranged from 1 to 14 days with an average of(5.24±1.35)days;they were treated once every other day for 2 weeks.There were 96 patients in control group,including 33 males and 63 females,aged from 26 to 60 years old with an average of(43.35±7.75)years old;the course of disease ranged from 1 to 14 days with an average of(5.86±1.48)days;they were treated with topical voltaalin combined with elbow joint fixation for 2 weeks.Visual analogue scale(VAS)and Hospital for Surgery Scoring System(HSS)elbow pronation and supination angles,wrist metacarpal flexion and dorsal extension angles,elbow tenderness between two groups were compared before treatment and at 1,3,5,7,11 and 13 days after treatment;Hospital for Surgery Scoring System 2(HSS2)was compared before treatment and the final treatment.Results All patients were followed up for 10 to 14 days with an average of(12±1.6)days.VAS between treatment group and control group before treatment were 6.83±1.36 and 6.79±1.58,respectively,and decreased to 1.49±1.09 and 2.11±1.81 after the final treatment.VAS of treatment group were significantly lower than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P＜0.05).HSS between two groups were 61.73±11.00 and 36.47±12.45 before treatment,respectively,and increased to 94.42±5.9 and 91.44±9.11 at the final treatment.HSS of treatment group were signifi-cantly higher than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P＜0.05).On the 5th day after treat-ment,the external and internal rotation angles of elbow in treatment group were(66.41±12.69)° and(66.35±13.54)°,while those in control group were(62.08±16.03)° and(61.77±16.35)°.On the 7th day after treatment,the external and internal ro-tation angles of elbow were(69.79±12.64)° and(70.02±13.55)° in treatment group,and(65.28±15.86)° and(65.09± 16.67)° in control group.Elbow joint motion in treatment group was higher than that in control group(P＜0.05).On the 5th day after treatment,angles of wrist dorsiflexion and palm flexion were(39.43±15.94)°and(46.68±11.10)° in treatment group,and(38.51±18.49)° and(44.27±13.58)° in control group.On the 7th day after treatment,angles of wrist dorsiflexion and palm flexion were(42.52±16.50)° and(49.23±10.96)° in treatment group,and(41.18±20.09)° and(46.64±14.63)° in control group.The motion of wrist joint in treatment group was higher than that in control group(P＜0.05).On the 13th day after treatment,HSS2 in treatment group 93.61±6.32 were higher than those in control group 92.06±7.94(P＜0.05).There was no significant difference in elbow tenderness between two groups at each time point(P＞0.05).Conclusion Voltaren external treatment combined with elbow fixation and tendons pulling,poking and kneading could effectively improve symptoms of exter-nal humeral epicondylitis.Compared with voltaren external treatment,tendons pulling,poking and kneading has advantages of longer analgesic time and better elbow function recovery.

Chronic lumbar and back pain caused by degenerative vertebral endplates presents a challenging issue for pa-tients and clinicians.As a new minimally invasive spinal treatment method,radiofrequency ablation of vertebral basal nerve in bone can denature the corresponding vertebral basal nerve through radiofrequency ablation of degenerative vertebral endplate.It blocks the nociceptive signal transmission of the vertebral base nerve,thereby alleviating the symptoms of low back pain caused by the degenerative vertebral endplate.At present,many foreign articles have reported the operation principle,opera-tion method,clinical efficacy and related complications of radiofrequency ablation of the vertebral basal nerve.The main pur-pose of this paper is to conduct a comprehensive analysis of the current relevant research,and provide a reference for the follow-up clinical research.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.