Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

AIM To investigate the protective effects and the mechanism of the Liuwei Dihuang Pills on mouse brain microvascular endothelial(bEnd.3)cells damaged by β-Amyloid protein1-40(Aβ1-40).METHODS CCK8 method was used to detect the effects of Aβ1-40 and medicated serum of Liuwei Dihuang Pills(MSLDP)on cell activity,and to screen the appropriate concentration.bEnd.3 cells of the control group,the Aβ1-40 group,the MSLDP+Aβ1-40 group and the MSLDP group had their low density lipoprotein-associated protein 1(LRP1),receptor for advanced glycation end products(RAGE),matrix metalloproteinase-2(MMP-2),MMP-9,scaffold protein zonule protein-1(ZO-1)detected by Western blot.bEnd.3 cells assigned into the control group,the Aβ1-40 group,the FPS-ZM1(RAGE inhibitor)+Aβ1-40 group and the FPS-ZM1+Aβ1-40+MSLDP group had their expressions of RAGE,MMP-9,MMP-2 and ZO-1 detected by Western blot as well.RESULTS The cell activity of bEnd.3,was dose-dependently decreased by Aβ1-40(P<0.01),but was protected by MSLDP(P<0.05,P<0.01).And 10 μmol/L Aβ1-40 and 10%MSLDP were selected for subsequent experiments.Compared with the control group,the Aβ1-40 group displayed increased protein expressions of RAGE,MMP-2 and MMP-9(P<0.01),decreased protein expressions of LRP1,ZO-1 and BDNF(P<0.05,P<0.01),and decreased fluorescence intensities of LRP1 and ZO-1(P<0.01).Compared with the Aβ1-40 group,the MSLDP group shared decreased expressions of RAGE,MMP-2,MMP-9 proteins and RAGE fluorescence intensity(P<0.05,P<0.01),and increased expressions of LRP1,ZO-1 and BDNF proteins,and the fluorescence intensity of LRP1 and ZO-1(P<0.05,P<0.01);the Aβ1-40+FPS-ZM1 group displayed decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.05,P<0.01),and increased ZO-1 protein expression(P<0.05);and the Aβ1-40+FPS-ZM1+ MSLDP group displayed an even more decreased protein expressions of MMP-2,MMP9 and RAGE(P<0.01),increased ZO-1 protein expression(P<0.01)due to the the combination use of FPS-ZM1 and MSLDP.CONCLUSION Liuwei Dihuang Pills can protect the tight junction of bEnd.3 injured by Aβ1-40 and neurovascular units from Alzheimer's disease by alleviating the dysfunction of the blood-brain barrier via RAGE-mediated MMP-2/MMP-9 pathway inhibition.

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 observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS). Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of 151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cfPWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling. Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2 rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a 19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions. Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

Objective To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation(MPR),and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population.Methods The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected.Volume reconstruction(VR)and MPR were performed on the skull,and 160 cranial suture tomography images were generated for each sample.Then the MPR images of cranial sutures were scored according to the closure grading criteria,and the mean closure grades of sagittal suture,coronal sutures(both left and right)and lambdoid sutures(both left and right)were calculated respectively.Finally taking the above grades as independent variables,the linear regression model and four machine learning models for age estimation(gradient boosting regression,support vector regression,decision tree regression and Bayesian ridge regression)were established for northern Chinese Han adults age estimation.The accu-racy of each model was evaluated.Results Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest.All four machine learning models had higher age estimation accuracy than linear regression model.The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years.Conclusion The combination of skull CT-MPR and machine learning model can be used for age esti-mation in northern Chinese Han adults,but it is still necessary to combine with other adult age estima-tion indicators in forensic practice.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To investigate clinical significance of WDR4 gene expression,prognosis and immune infiltration in lung adenocarcinoma(LUAD).Methods:Clinicopathological data and WDR4 mRNA expression data of 535 patients with LUAD were collected through TCGA database,WDR4 protein expression data of 111 patients with LUAD were collected through CPTAC database.Associations between WDR4 expression and various clinicopathological features,as well as with overall survival in LUAD were ana-lyzed by R software.Diagnostic value of WDR4 expression in LUAD were assessed by ROC.Correlation between WDR4 expression and immune infiltration in tumor microenvironment in LUAD were investigated by Estimates and ssGSEA algorithms.Results:WDR4 mRNA expression in LUAD was significantly higher than that in normal lung tissues(all P<0.001).Protein expression of WDR4 in LUAD was also significantly up-regulated(P<0.05).Univariate analysis showed that expression of WDR4 was correlated with lymph node metastasis(P<0.05).Log-rank test showed that overall survival of patients with LUAD in WDR4 high expression group was significantly lower than that in low expression group(P=0.004).Multivariate Cox analysis revealed that T stage,lymph node metasta-sis and WDR4 mRNA expression remained independently associated with prognosis of LUAD patients.Death risk in patients with high expression of WDR4 mRNA was 1.478 times that of patients with low expression(95%CI:1.041～2.097).ROC curve analysis showed that WDR4 mRNA expression predicted diagnosis of LUAD to high extent(AUC=0.912,95%CI:0.885～0.935).High expression of WDR4 was negatively correlated with tumor microenvironment immune infiltration(all P<0.05).Conclusion:WDR4 expression in LUAD is significantly higher than that in normal lung tissue,and high WDR4 expression indicates poor prognosis in patients with LUAD.High expression of WDR4 inhibits immune infiltration in tumor microenvironment.WDR4 may be a novel potential biomarker for diagnosis and prognosis of patients with LUAD and therapeutic target.

Objective:To investigate the risk factors for severe distal curve progression after posterior hemivertebra (HV) resection and short-segment fixation in patients with congenital cervicothoracic scoliosis (CTS), and to analyze the surgical revision strategy.Methods:Imaging and clinical data of patients who underwent posterior HV resection and short-segment fixation for CTS between August 2012 and August 2021 at Nanjing Drum Tower Hospital were retrospectively analyzed. A total of 55 patients were recruited, including 27 females and 28 males with an average age of 8.5±3.6 years (range 3-15 years) at surgery and an average Risser grade of 0.7±1.4 (range 0-4). The number of fused segments averaged 6.9±1.6 (range 4-10), and the mean follow-up was 38.7±18.9 months (range 9-94 months). According to the severity of distal curve progression, the recruited patients were divided into three groups: non-progression group (NPG), mild progression group (MPG), and severe progression group (SPG). The latter two groups were collectively called the progression group (PG). The cervicothoracic Cobb angle, T1 tilt angle, coronal balance distance (CBD), neck tilt angle, clavicular angle, head tilt angle, head shift, and upper (UIV) and lower instrument vertebra (LIV) tilt angle on the standing whole spine X-ray were measured before and after surgery and at the last follow-up. The correction rate of the Cobb angle in the osteotomy area was measured and calculated on CT three-dimensional reconstruction, and the proportion of patients with Klippel-Feil syndrome (KFS) was recorded. Statistical analysis was conducted on the various parameters between the two groups. For factors with statistical significance in the single-factor analysis, binary logistic regression analysis was performed to identify the high-risk factors for distal curve progression.Results:There were 38 cases in the NPG, 11 in the MPG, and 6 in the SPG. Compared to the NPG, the PG showed more severe coronal imbalance preoperatively, with CBD of 35.6±22.3 mm and 11.6±7.1 mm respectively; more severe neck tilt and head shift, with neck tilt angle of 17.4°±8.3° and 12.4°±6.9° respectively, and head shift of 22.8±17.7 mm and 13.9±9.8 mm respectively; and a higher proportion of KFS, 65% (11/17) and 34% (13/38) respectively, all with statistical significance ( P<0.05). Postoperatively, the PG showed more severe coronal imbalance compared with the NPG, with 17.3±12.7 mm and 9.6±8.1 mm respectively; more evident residual deformity, with cervical tilt angles of 9.4°±4.6° and 6.4°±5.3° respectively, and head shift of 14.7±7.4 mm and 9.1±5.9 mm respectively; lower correction of Cobb angle in the apical osteotomy region, with rates of 40.1%±15.2% and 50.3%±19.9% respectively; more significant UIV and LIV tilt, with UIV tilt angles of 14.3°±7.4° and 9.8°±5.3° respectively, and LIV tilt angles of 8.1°±5.5° and 4.5°±3.6° respectively, all with statistical significance ( P<0.05). SPG showed only more severe coronal imbalance preoperatively compared with the MPG, with 50.7±31.3 mm and 27.3±9.6 mm respectively; and head shift, with 33.5±25.0 mm and 16.9±11.0 mm respectively, all with statistical significance ( P<0.05). Logistic regression analysis demonstrated a significant correlation between significant preoperative coronal imbalance and postoperative distal scoliosis progression [ OR=1.299, 95% CI (1.101, 1.531), P=0.002]. Five cases (83.3%) in SPG underwent revision surgery with an average follow-up of 25 months, and selecting the LIV down to the stable region was the major revision strategy. Conclusion:Combined KFS, residual cervicothoracic deformities, and tilting of UIV and LIV are key causes, whereas significant preoperative coronal imbalance is an independent risk factor predisposing to the distal curve progression.