This paper summarized Professor PI Chiheng's experience in treating diabetic nephropathy （DN） using the method of warming yang， nourishing yin， and invigorating blood by stages. It is believed that yang deficiency and yin depletion are the key pathological mechanisms of DN， with blood stasis running throughout the disease's progression. The general treatment principle is to warm yang， nourish yin， and invigorate blood， with different emphases at each stage. For early stage， the disease is characterized by spleen qi deficiency and insufficiency of qi and yin， which could be treated by modified Shenqi Dihuang Decoction （参芪地黄汤） to tonify qi and invigorate blood， strengthen yang and consolidate yin； for middle stage， the disease is marked by spleen and kidney yang deficiency with internal dampness accumulation， which could be treated by modified Zhenwu Decoction （真武汤） and Sanren Decoction （三仁汤） warming yang and to resolve dampness and unblock meridians； for the late stage， the disease is characterized by blood stasis and toxin accumulation with deficiency of both yin and yang， which could be treated by modified Jisheng Shenqi Pill （济生肾气丸） to eliminate pathological masses and remove toxins， warm yang and nourish yin. Additionally， traditional Chinese medicine therapies such as rubbing with ointment （Gao Mo therapy） are utilized as adjunct treatments， treating the root and branch simultaneously and combining internal and external approaches.

OBJECTIVE: To investigate whether adding 1 transverse screw (TS) to the triangular parallel cannulated screw (TPCS) fixation has a mechanical stability advantage for Pauwels type Ⅲ femoral neck fractures by conducting finite element analysis on four internal fixation methods. METHODS: Based on CT data of a healthy adult male volunteer's femur, three Pauwels type Ⅲ femoral neck fracture models (Pauwels angle 70°, Pauwels angle 80°, and Pauwels angle 70° combined with bone defect) were constructed using Mimics 21.0 software and SolidWorks 2017 software. Four different internal fixation models were built at the same time, including TPCS, TPCS+TS, three cross screws (TCS), and TPCS+medial buttress plate (MBP). The mechanical stability of different models under the same load was compared by finite element analysis. RESULTS: The femoral model established in this study exhibited a maximum stress of 28.62 MPa, with relatively higher stress concentrated in the femoral neck. These findings were comparable to previous studies, indicating that the constructed femoral finite element model was correct. The maximum stress of internal fixation in finite element analysis showed that TCS was the lowest and TPCS+MBP was the highest in Pauwels angle 70° and 80° models, while TPCS+TS was the lowest and TCS was the highest in Pauwels angle 70° combined with bone defect model. The maximum displacement of internal fixation in each fracture model was located at the top of the femoral head, with TCS having the highest maximum displacement of the femur. The maximum stress of fracture surface in finite element analysis showed that TCS was the lowest and TPCS was the highest in the Pauwels angle 70° model, while TPCS+MBP was the lowest and TPCS/TCS were the highest in the Pauwels angle 80° model and the Pauwels angle 70° combined with bone defect model, respectively. The maximum displacement of fracture surfece analysis showed that TPCS+MBP was the lowest and TCS was the highest in Pauwels angle 70° and 80° models, while TPCS+TS was the lowest and TCS was the highest in Pauwels angle 70° combined with bone defect model. CONCLUSION For Pauwels type Ⅲ femoral neck fractures, the biomechanical stability of TPCS+TS was superior to that of TPCS alone and TCS, but it has not yet reached the level of TPCS+MBP.
Finite Element Analysis ; Humans ; Femoral Neck Fractures/diagnostic imaging* ; Bone Screws ; Fracture Fixation, Internal/instrumentation* ; Male ; Bone Plates ; Stress, Mechanical ; Biomechanical Phenomena ; Tomography, X-Ray Computed ; Adult ; Femur Neck/surgery*

As activated hepatic stellate cells (aHSCs) play a central role in fibrogenesis, they have become key target cells for anti-fibrotic treatment. Nevertheless, the therapeutic efficiency is constrained by the exosomes they secrete, which are linked to energy metabolism and continuously stimulate the activation of neighboring quiescent hepatic stellate cells (qHSCs). Herein, an intercellular communication interference strategy is designed utilizing paeoniflorin (PF) loaded and hyaluronic acid (HA) coated copper-doped ZIF-8 (PF@HA-Cu/ZIF-8, PF@HCZ) to reduce energy-related exosome secretion from aHSCs, thus preserving neighboring qHSCs in a quiescent state. Simultaneously, the released copper and zinc ions disrupt key enzymes involved in glycolysis to reduce bioenergy synthesis in aHSCs, thereby promoting the reversion of aHSCs to a quiescent state and further decreasing exosome secretion. Therefore, PF@HCZ can effectively sustain both aHSCs and qHSCs in a metabolically dormant state to ultimately alleviate liver fibrosis. The study provides an enlightening strategy for interrupting exosome-mediated intercellular communication and remodeling the energy metabolic status of HSCs with boosted antifibrogenic activity.

Group A Streptococcus (GAS) are important human pathogens.In recent years, the M1 UK strain has attracted widespread attention in the United Kingdom and other countries because it has been associated with a surge in scarlet fever and an increase in invasive GAS infections.Author conducted a whole-genome sequencing study of 42 GAS strains from 2016 to 2018 in Shenzhen, and found that a GAS strain isolated from a child with scarlet fever in Shenzhen area in 2018 was homologous to M1 UK, which is the first strain of M1 UK confirmed in the mainland of China.For this reason, hereby publish it with a view to attracting the attention of our domestic counterparts and safeguarding public health safety.

Objective:To explore the risk factors for lymphoproliferative disorders (PTLD) in children with thalassemia major (TM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:This was a retrospective case-control study.A total of 482 children with TM who underwent allo-HSCT at Shenzhen Children′s Hospital between January 2020 and December 2022 were selected and classified into the PTLD and non-PTLD groups according to the occurrence of PTLD.The risk factors for PTLD after allo-HSCT in children with TM were analyzed, and the diagnostic efficiency of relevant risk factors for PTLD was analyzed by receiver operating characteristic (ROC) curve.Results:A total of 25 out of 482 patients (5.2%, 25/482) developed PTLD about 114 (54-271) days after allo-HSCT.Among them, 12 cases (12/25, 48.0%) occurred within 100 days, and 22 cases (22/25, 88.0%) occurred within 1 year after allo-HSCT.Univariate analysis showed that there were significant differences in gender composition, type of transplant donor, number of natural killer cells and B lymphocytes in peripheral blood at 30 days after allo-HSCT, positive rate of plasma Epstein-Barr virus deoxyribonucleic acid (EBV-DNA) and incidence rate of acute graft-versus-host disease (aGVHD) between the 2 groups (all P<0.05).Multivariate Logistic regression analysis showed that female ( OR=3.196, 95% CI: 1.144-8.929), positive plasma EBV-DNA ( OR=17.523, 95% CI: 5.449-56.344) and aGVHD ( OR=3.156, 95% CI: 1.161-8.575) were independent risk factors for PTLD after allo-HSCT in TM children (all P<0.05).The ROC curve analysis showed that positive plasma EBV-DNA had an excellent accuracy in predicting the occurrence of PTLD after allo-HSCT (sensitivity was 0.796, specificity was 0.800, area under the curve was 0.803).If combined with aGVHD and gender, the area under the curve for the prediction of PTLD increased to 0.831. Conclusions:Female, positive plasma EBV-DNA and aGVHD are independent risk factors for PTLD after allo-HSCT in children with TM.It provides useful early warnings for the prediction and prevention of PTLD.

BACKGROUND:Myocardial infarction is one of the most serious cardiovascular diseases at present,and the existing clinical treatment options such as thrombolytic therapy,percutaneous coronary intervention and coronary artery bypass grafting cannot fully restore the myocardial damage caused by ischemia.Stem cell-derived exosomes for the treatment of myocardial infarction have been a hot research topic in recent years,but the low yield of natural-derived exosomes,the difficulty and time consuming nature of obtaining them,and the poor homing effect have limited their clinical application.In this context,the construction of artificial exosomes as an alternative to natural exosomes has become an effective strategy to solve the above problems. OBJECTIVE:To expound the research status of artificial exosomes in the treatment of myocardial infarction,and classify them into two design modes:semi-artificial and full-artificial,and discuss the research progress and problems of the two modes,finally,make the evaluation and prospect of its clinical application in the future. METHODS:PubMed and CNKI were searched for relevant articles with"artificial exosomes,myocardial infarction,engineering"in Chinese,and"artificial exosome,hybrid exosome,myocardial infarction,nanoparticle,drug delivery system"in English.The focus of the search was from January 2017 to December 2022,and some of the classic forward literature was included.A preliminary selection was conducted through reading titles and abstracts.Repetitive studies,low-quality journals and irrelevant articles were excluded.Finally,73 articles were included for review. RESULTS AND CONCLUSION:(1)By semi-artificially modifying exosomes,whether it is the modification of targeting peptides,hybridization of biofilms or the assistance of magnetic substances,traditional exosome therapies with insufficient targeting and low retention rate and easy to be cleared by the reticuloendothelial system have improved the efficiency of traditional exosome therapy for myocardial infarction.However,these strategies have problems such as unclear modification efficiency,medical ethics,and biotoxicity.(2)Fully artificial bionic exosomes have a higher degree of design freedom compared to exosome modification,which can solve the problems of high extraction and storage difficulties of exosomes of natural origin and limitations of large-scale production;however,this artificial exosome strategy still lacks reliable preclinical data support and biosafety testing,and has not yet formed a standardized process required for large-scale production;therefore,before applying to the clinic,the artificial exosome solution as an alternative to natural exosomes still needs continuous in-depth research by researchers.

Objective: To investigate the ability of radiological parameter canal bone ratio (CBR) to assess bone mineral density and to differentiate between patients with primary and multiple osteoporotic vertebral compression fracture (OVCF). Methods: A retrospective analysis was conducted on OVCF patients treated at our hospital. CBR was measured through full-spine x-rays. Patients were categorized into primary and multiple fracture groups. Receiver operating characteristic curve analysis and area under the curve (AUC) calculation were used to assess the ability of parameters to predict osteoporosis and multiple fractures. Predictors of T values were analyzed by multiple linear regression, and independent risk factors for multiple fractures were determined by multiple logistic regression analysis. Results: CBR showed a moderate negative correlation with dual-energy x-ray absorptiometry T values (r = -0.642, p < 0.01). Higher CBR (odds ratio [OR], -6.483; 95% confidence interval [CI], -8.234 to -4.732; p < 0.01) and lower body mass index (OR, 0.054; 95% CI, 0.023–0.086; p < 0.01) were independent risk factors for osteoporosis. Patients with multiple fractures had lower T values (mean ± standard deviation [SD]: -3.76 ± 0.73 vs. -2.83 ± 0.75, p < 0.01) and higher CBR (mean ± SD: 0.54 ± 0.07 vs. 0.46 ± 0.06, p < 0.01). CBR had an AUC of 0.819 in predicting multiple fractures with a threshold of 0.53. T values prediction had an AUC of 0.816 with a threshold of -3.45. CBR > 0.53 was an independent risk factor for multiple fractures (OR, 14.66; 95% CI, 4.97–43.22; p < 0.01). Conclusion CBR is negatively correlated with bone mineral density (BMD) and can be a novel opportunistic BMD assessment method. It is a simple and effective measurement index for predicting multiple fractures, with predictive performance not inferior to T values.

Objective:To investigate the mechanism of downregulated programmed cell death 10 ( PDCD10) expression mediating glioblastoma multiforme (GBM) resistance to temozolomide (TMZ). Methods:U87, LN229 and T98g cell lines were transfected with PDCD10 small interfering RNA or negative small interfering RNA. TMZ-resistant cell lines were constructed using 300 μmol/L TMZ (transfected T98g cell line) and 150 μmol/L TMZ (transfected U87 and LN229 cell lines), respectively: TMZ-resistant U87 cell line transfected with PDCD10 small interfering RNA (shPDCD10-U87-RG cells), TMZ-resistant U87 cell line transfected with negative small interfering RNA (EV-U87-RG cells), shPDCD10-T98g-RG cells, EV-T98g-RG cells, shPDCD10-LN229-RG cells and EV-LN229-RG cells. Flow cytometry and real-time quantitative polymerase chain reaction (qRT-PCR) were used to detect the transfection efficiency of TMZ-resistant cell lines and PDCD10 expressions; MTT assay and colony formation assay were used to verify the drug-resistant ability of TMZ-resistant cell lines. Bioinformatics analysis was performed to detect the correlations of PDCD10 with key genes ( MSH6 and PMS2) in mismatch repair (MMR) system, and drug resistant mechanism was explored by detecting the cell cycle and neurosphere formation ability of drug-resistant cells. Results:(1) qRT-PCR showed that compared with that in EV-U87-RG cells, the PDCD10 expression in shPDCD10-U87-RG cells was statistically down-regulated by (32.85±1.14)% ( t=2.925, P=0.049); compared with that in EV-T98g-RG cells, the PDCD10 expression in shPDCD10-T98g-RG cells was significantly down-regulated by (57.17±1.81)% ( t=3.179, P=0.043); compared with that in EV-LN229-RG cells, the PDCD10 expression in shPDCD10-LN229-RG cells was significantly down-regulated by (33.68±1.34)% ( t=3.085, P=0.045). (2) MTT assay showed that compared with the EV-U87-RG cells, the shPDCD10-U87-RG cells had significantly increased viability ( P<0.05); compared with the EV-T98g-RG cells, the shPDCD10-T98g-RG cells had significantly increased viability ( P<0.05). Among the same kind of cells, the viability 3 d after wash-out was significantly increased compared with that at 72 h after TMZ treatment ( P<0.05). Colony formation assay showed that cell lines with down-regulated PDCD10 expression had higher tumorigenic ability. (3) Compared with EV-U87-RG cells and EV-T98g-RG cells, cells with down-regulated PDCD10 expression (shPDCD10-U87-RG cells and shPDCD10-T98g-RG cells) escaped from TMZ-induced G2/M arrest, resulting in TMZ resistance. (4) Bioinformatics analysis revealed that the PDCD10 expression was positively correlated with MSH6 and PMS2 expressions ( r=0.262, P<0.001; r=0.327, P<0.001); qRT-PCR indicated that downregulated PDCD10 expression caused decreased MSH6 and PMS2 expressions, which disrupted the MMR system. (5) Compared with that by EV-U87 cells, number of neurospheres formed by shPDCD10-U87 cells was significantly increased ( P<0.05); compared with that by EV-U87-RG cells, number of neurospheres formed by shPDCD10-U87-RG cells was significantly increased ( P<0.05). Conclusion:PDCD10 affects the therapeutic sensitivity of GBM to TMZ by arresting cell cycle, disrupting MMR system, and increasing cell stemness.

Objective: To investigate the ability of radiological parameter canal bone ratio (CBR) to assess bone mineral density and to differentiate between patients with primary and multiple osteoporotic vertebral compression fracture (OVCF). Methods: A retrospective analysis was conducted on OVCF patients treated at our hospital. CBR was measured through full-spine x-rays. Patients were categorized into primary and multiple fracture groups. Receiver operating characteristic curve analysis and area under the curve (AUC) calculation were used to assess the ability of parameters to predict osteoporosis and multiple fractures. Predictors of T values were analyzed by multiple linear regression, and independent risk factors for multiple fractures were determined by multiple logistic regression analysis. Results: CBR showed a moderate negative correlation with dual-energy x-ray absorptiometry T values (r = -0.642, p < 0.01). Higher CBR (odds ratio [OR], -6.483; 95% confidence interval [CI], -8.234 to -4.732; p < 0.01) and lower body mass index (OR, 0.054; 95% CI, 0.023–0.086; p < 0.01) were independent risk factors for osteoporosis. Patients with multiple fractures had lower T values (mean ± standard deviation [SD]: -3.76 ± 0.73 vs. -2.83 ± 0.75, p < 0.01) and higher CBR (mean ± SD: 0.54 ± 0.07 vs. 0.46 ± 0.06, p < 0.01). CBR had an AUC of 0.819 in predicting multiple fractures with a threshold of 0.53. T values prediction had an AUC of 0.816 with a threshold of -3.45. CBR > 0.53 was an independent risk factor for multiple fractures (OR, 14.66; 95% CI, 4.97–43.22; p < 0.01). Conclusion CBR is negatively correlated with bone mineral density (BMD) and can be a novel opportunistic BMD assessment method. It is a simple and effective measurement index for predicting multiple fractures, with predictive performance not inferior to T values.