BACKGROUND:In the initial stage of growth plate injury inflammation,platelet-derived growth factor BB promotes the repair of growth plate injury by promoting mesenchymal progenitor cell infiltration,chondrogenesis,osteogenic response,and regulating bone remodeling. OBJECTIVE:To elucidate the action mechanism of platelet-derived growth factor BB after growth plate injury. METHODS:PubMed,VIP,WanFang,and CNKI databases were used as the literature sources.The search terms were"growth plate injury,bone bridge,platelet-derived growth factor BB,repair"in English and Chinese.Finally,66 articles were screened for this review. RESULTS AND CONCLUSION:Growth plate injury experienced early inflammation,vascular reconstruction,fibroossification,structural remodeling and other pathological processes,accompanied by the crosstalk of chondrocytes,vascular endothelial cells,stem cells,osteoblasts,osteoclasts and other cells.Platelet-derived growth factor BB,as an important factor in the early inflammatory response of injury,regulates the injury repair process by mediating a variety of cellular inflammatory responses.Targeting the inflammatory stimulation mediated by platelet-derived growth factor BB may delay the bone bridge formation process by improving the functional activities of osteoclasts,osteoblasts,and chondrocytes,so as to achieve the injury repair of growth plate.Platelet-derived growth factor BB plays an important role in angiogenesis and bone repair tissue formation at the injured site of growth plate and intrachondral bone lengthening function of uninjured growth plate.Inhibition of the coupling effect between angiogenesis initiated by platelet-derived growth factor BB and intrachondral bone formation may achieve the repair of growth plate injury.

OBJECTIVE To investigate the effect of bs-5-YHEDA iron chelating peptide combined with semaglutide on the cognitive ability and pathological characteristics of D-Gal-induced Alzheimer's disease(AD) model mice. METHODS Forty mice were randomly divided into 5 groups, namely the healthy control group, PBS group, bs-5-YHEDA iron chelating peptide group, combined treatment group and positive control group, with 8 mice in each group, half of each sex. Except for the healthy control group, D-galactose was injected to induce the AD mice model for 6 weeks. For 3 consecutive weeks starting from the 4th week, the bs-5-YHEDA iron chelating peptide group was injected with bs-5-YHEDA(1 mg·mL–1) once every other day at 200 µL in the tail vein; the bs-5-YHEDA iron chelating peptide(1 mg·mL–1) and semaglutide(25 nmol·kg–1·d–1) were given alternately once a day in the combination treatment group; the positive control group was given memantine(3.3 mg·kg–1·d–1) by gavage every other day. The healthy control group and PBS group were injected with the equal dose of PBS. At the end of treatment, the learning memory ability of mice was detected by the Morris water maze method, whole brain and whole blood were dissected, and pathological changes in hippocampal region were observed by HE staining, and Aβ expression and Tau protein phosphorylation levels were detected by immunohistochemistry, enzyme-linked immunosorbent assay and immunoblotting. RESULTS In the Morris water maze spatial exploration experiment, the differences in the number of times the mice traversed the platform, the ratio of swimming distance to the target quadrant, and the time ratio were statistically significant in each group(P<0.05); compared with the PBS group, the ratio of swimming distance to the target quadrant increased in the combined treatment group, and the differences were statistically significant(P<0.05). The results of HE staining showed that compared with the healthy control mice, the hippocampal area in the PBS group showed reduced levels of pyramidal cells, disorganized arrangement, cell edema, and deep staining of nuclei consolidation. Cellular disorganization, deep staining of nuclei and apoptosis in the hippocampus were significantly improved in each treatment group after drug treatment. Immunohistochemistry and Western blotting results showed that the Aβ expression levels and Tau protein phosphorylation levels were significantly higher in the PBS-administered mice compared with the healthy control mice, and the Aβ expression levels and Tau protein phosphorylation levels were reduced in each group after drug treatment, with statistically significant differences(P<0.01 or P<0.001 ). CONCLUSION The combination of bs-5-YHEDA iron chelating peptide and semaglutide can effectively improve the learning and memory ability and pathological characteristics of AD mice, but from the results of immunohistochemistry and immunoblotting experiments, the improvement of pathological characteristics of AD mice in the combination treatment group is not obvious compared with the single bs-5-YHEDA iron chelating peptide group, suggesting that there may be a threshold effect of our designed dual-target combination treatment on the cognitive improvement of AD mice, and the optimization and validation of the effect of multi-target combination treatment need further study.

Objective:To investigate the mechanism of immunomodulatory effects of umbilical cord mesenchymal stem cells(UC-MSCs)modified by miR-125b-5p on systemic lupus erythematosus(SLE).Methods:The expression level of miR-125b-5p was detected by real-time fluorescence quantitative PCR in UC-MSCs and peripheral blood mononuclear cells(PBMCs)from SLE patients and health checkers.Annexin V-FITC/PI apoptosis detection kit was used to detect the effect of miR-125b-5p on apoptosis of UC-MSCs.MRL/lpr mice in each group were injected with UC-MSCs via tail vein,and T-lymphocyte subsets in the spleen of the MRL/lpr mice were detected by flow cytometry after 5 weeks.The expression levels of interleukin(IL)-4 and IL-17A in serum of MRL/lpr mice were detected by ELISA.Hematoxylin-eosin staining was used to observe the pathological manifestations of the lungs and kidneys of the MRL/lpr mice.Results:miR-125b-5p was significantly down-regulated in PBMCs of SLE patients compared with healthy controls(P＜0.01).Compared with the UC-MSCs group,the expression of miR-125b-5p in UC-MSCs modified by miR-125b-5p group was increased(P＜0.01).The survival rate of UC-MSCs was significantly increased by miR-125b-5p(P＜0.01).Compared with the untreated group of MRL/lpr mice,the expression level of IL-4 in serum was increased(P＜0.05);the expression level of IL-17A was decreased(P＜0.05);the proportion of Th17 cells in the spleen of MRL/lpr mice was decreased(P＜0.05);the inflammatory cells infiltration and micro-thrombosis of lungs and kidneys of MRL/lpr mice were significantly reduced in the UC-MSCs modified by miR-125b-5p treatment group.Conclusion:UC-MSCs modified by miR-125b-5p have immunomodulatory effects on systemic lupus erythematosus.

Mechanical ventilation(MV)provides life support for critically ill respiratory patients,but in the meantime can cause fatal ventilator-induced lung injury(VILI),and the latter remains a major challenge in respiratory and critical care medicine,because the pathological mechanism has not been fully elucidated.Recent studies show that on the one hand,in the lung with VILI,there exists airway collapse at multi-sites of an individual airway,which can not be explained by traditional airway collapse models.But on the other hand,under MV conditions,airway smooth muscle cells(ASMC)exhibit abnormal mechanical behaviors,accompanied by regulation of Piezo1 expression and endoplasmic reticulum stress.These phenomenons indicate that the MV-induced abnormal mechanical behavior of ASMC is closely related to multiple airway collapse and VILI.Therefore,by studying the MV-induced changes of ASMC mechanical behaviors and their relationship with airway collapse in lung injury,as well as the related mechanochemical signal coupling process,it is expected to reveal a novel mechanism of MV-associated airway collapse and lung injury from the perspective of cell mechanics.In this review,the recent research progress of airway collapse during MV,the regulation of ASMC mechanical behavior by MV-related high stretch,especially the related mechanochemical signal coupling mechanism is summarized.These advances may provide a novel insight for exploring the roles of ASMC abnormal mechanical behavior in the pathological mechanism of VILI,alternative targets of drug intervention for prevention and treatment of VILI,as well as for optimizing the ventilation mode in clinical practice.

Objective:To investigate the efficacy and safety of separated R-CHOP in older patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL).Methods:A total of 137 patients aged 65-80 years newly diagnosed with DLBCL between April 2013 and September 2022 at The First Affiliated Hospital of Zhengzhou University were enrolled.The patients were assigned into separated R-CHOP,full-dose R-CHOP,and reduced R-CHOP-like groups based on their different chemotherapy regimens.All individuals were treated in 21-day cycles for 4-8 cycles.The short-term and long-term efficacies and adverse reactions of the treatments were compared among the three groups,and factors influencing progression-free survival(PFS)and overall survival(OS)were analyzed.Results:The overall response rates(ORR)of patients in the separated R-CHOP,full-dose R-CHOP,and reduced R-CHOP-like groups were 89.7%,90.3%,and 86.1%,respectively,with no significant differences among them.The complete respond rate(CRR)of the separated R-CHOP group(64.1%)was significantly higher than that of the reduced R-CHOP-like group(33.3%)(P=0.008)but not significantly different from that of the full-dose R-CHOP group(66.1%).Survival curve analysis revealed no significant differences in PFS and OS between the separated and full-dose R-CHOP groups.Although the separated R-CHOP group showed improved PFS compared with the reduced R-CHOP-like group(P=0.036),there was no statistical difference in OS between these two groups.Multivariate analysis revealed that the international prognostic index(IPI)and separated R-CHOP had significant effects on PFS in patients with DLBCL(all P<0.05),whereas only IPI had a significant effect on OS(P<0.001).The incidence of leukopenia and grade 3-4 leukopenia in the separated R-CHOP group was significantly lower than that in the full-dose R-CHOP group(P=0.007,P=0.012),but there was no significant difference with the reduced R-CHOP-like group in this regard.Conclusions:In older patients with newly diagnosed DLBCL,separated R-CHOP showed good efficacy both in the short and long terms and had acceptable safety and tolerability profiles.

Objective:To investigate the association between serum lipid levels and inflammatory indicators in patients with primary open angle glaucoma (POAG).Methods:A case-control study was conducted.A total of 86 POAG subjects were collected as a POAG group at Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong from January 2016 to March 2022.Meanwhile, 86 with age-related cataract only, matched at age, sex and body mass index were collected as a control group.The intraocular pressure (IOP) and the mean defect of visual field (MD) were measured by Goldmann tonometer and Humphrey field analyzer, respectively.Human peripheral blood samples collected from subjects for serum lipid levels, including total cholesterol, total triglycerides, high density lipoprotein (HDL), and low density lipoprotein (LDL), were analyzed using an automated hematology analyzer and inflammatory markers including C-reactive protein, white blood cells (WBC), neutrophils, lymphocytes, monocytes, were analyzed using an automated biochemical analyzer.Indicators with statistically significant differences between the two groups were selected as independent variables, and multiple logistic regression analysis was used to determine the risk factors for POAG.Correlations between risk factors and ocular parameters (IOP and MD) were assessed using Pearson correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong (No.EC20210313[2]-P03). Written informed consent was obtained from each patient before any medical examination.Results:The HDL was (1.59±0.42)mmol/L in the POAG group, which was significantly lower than (1.76±0.50)mmol/L in the control group ( t=2.435, P=0.016). The LDL was (3.34±0.66)mmol/L in the POAG group, which was significantly higher than (3.08±0.71)mmol/L in the control group ( t=2.520, P=0.013). The WBC was (6.91±1.60)×10 9/L in the POAG group, which was significantly higher than (6.11±1.29)×10 9/L in the control group ( t=3.619, P<0.001). Multiple logistic regression analysis showed that high serum LDL level ( P=0.039, OR=2.354, 95% CI: 1.105-5.303) and high WBC level ( P=0.044, OR=1.310, 95% CI: 1.007-1.703) were risk factors for POAG.Pearson correlation analysis showed that the serum LDL and WBC levels of POAG patients were moderately positively associated with IOP ( r=0.610, P<0.001; r=0.358, P=0.001). LDL level was moderately negatively associated with MD ( r=-0.496, P<0.001). WBC level was weakly negatively associated with MD ( r=-0.235, P=0.030). Conclusions:The elevated peripheral blood LDL and WBC levels are risk factors for POAG onset.The elevated LDL and WBC levels are positively correlated with IOP and negatively correlated with MD in POAG patients.

Viruses are powerful tools for the study of modern neurosciences. Most of the research on the connection and function of neurons were done by using recombinant viruses, among which neurotropic herpesvirus is one of the most important tools. With the continuous development of genetic engineering and molecular biology techniques, several recombinant neurophilic herpesviruses have been engineered into different viral tools for neuroscience research. This review describes and discusses several common and widely used neurophilic herpesviruses as nerve conduction tracers, viral vectors for neurological diseases, and lytic viruses for neuro-oncology applications, which provides a reference for further exploring the function of neurophilic herpesviruses.
Herpesviridae/genetics* ; Neurosciences ; Genetic Vectors/genetics* ; Genetic Engineering ; Neurons

Objective : To investigate the imunomodulatory effects of umbilical cord mesenchymal stem cells(UC⁃MSCs) modified by miR⁃125b⁃5p through JAK2/STAT3 pathway on systemic lupus erythematosus(SLE) . Methods: UC⁃MSCs were isolated and cultured under aseptic conditions ; Peripheral blood mononuclear cells ( PBMCs)were separated from SLE patients by density gradient centrifugation. The relative expressions of IL⁃17A , Foxp3 ,IFN⁃γ , IL⁃4 genes in PBMCs cultured with UC⁃MSCs for 48 h were detected by RT⁃qPCR; The relative expressions of JAK2 , p ⁃JAK2 , STAT3 , p ⁃STAT3 and IL⁃18 proteins in kidney tissues of MRL/lpr mice were detected by west⁃ern blot. Results : Compared with the PBMCs culture group , the expression of IFN⁃γ and IL⁃17A and the propor⁃tion of Th17/Treg cells were significantly down⁃regulated in UC⁃MSCs + miR⁃125b⁃5p group , UC⁃MSCs + miR⁃NC group and UC⁃MSCs group(P < 0. 01) , the expression of the proportion of Th1/Th2 cells (P < 0. 05) was down⁃regulated in UC⁃MSCs + miR⁃125b⁃5p group and UC⁃MSCs + miR⁃NC group ; Compared with the untreated group of MRL/lpr mice , the relative expressions of JAK2 , p ⁃JAK2 , STAT3 , p ⁃STAT3 and IL⁃18 proteins in kidney tissues of MRL/lpr mice were significantly down⁃regulated in UC⁃MSCs + miR⁃125b⁃5p group (P < 0. 01) , and the rela⁃tive expressions of IL⁃18 proteins was significantly down⁃regulated in UC⁃MSCs + miR⁃NC group and UC⁃MSCs group (P < 0. 01) . Conclusion miR⁃125b⁃5p plays a synergistic role in UC⁃MSCs ,which regulates the differenti⁃ation of Th2 cells in PBMCs of SLE patients and the relative expressions of p ⁃JAK2/JAK2 , p ⁃STAT3/STAT3 , and IL⁃18 proteins in kidney tissues of MRL/lpr mice. UC⁃MSCs modified by miR⁃125b⁃5p may play immunomodulato⁃ry effect on SLE by JAK2/STAT3 signaling pathway.

Objective:To improve the therapeutic regimen for mantle cell lymphoma,we investigated the efficacy and safety of adding a BTK inhibitor to a regimen including rituximab,bendamustine,cytarabine,and prednisone to treat patients with mantle cell lymphoma(MCL).Methods:Twenty-six patients newly diagnosed with MCL who were admitted to The First Affiliated Hospital of Zhengzhou University from March 2021 to November 2023 were treated with a regimen of rituximab,bendamustine,cytarabine and prednisone combined with a BTK inhibitor,and the efficacy and adverse effects of this regiment were retrospectively analyzed.Results:The median age of the 26 newly dia-gnosed MCL patients was 59(41-72)years.The cohort included 22 males and 4 females,and the median follow-up time was 12(3-28)months.The overall response rate(ORR)was 92.3%and the complete response rate(CRR)was 88.5%.Median progression-free survival(PFS)and median overall survival(OS)endpoints were not achieved,with a 1-year PFS rate of 81.25%and a 1-year OS rate of 92.3%.A bet-ter PFS was achieved in the low mantle cell lymphoma International Prognostic Index(MIPI)score(0-3 points)group than in the high MIPI score(4-11 points)group(P=0.020).PFS was better in the group without B symptoms than in the group with B symptoms(P=0.002).PFS was better in the classical group than in the pleomorphic-blastoid subtype group(P=0.009).The main adverse effects were lymphopenia and thrombocytopenia.No treatment-related serious adverse events were observed during the follow-up period.Conclusions:The regimen of rituximab,bendamustine,cytarabine,and prednisone in combination with BTK inhibitors is safe and effective for the treatment of newly dia-gnosed patients with MCL.

Objective To retrospectively evaluate the clinical efficacy and safety of brentuximab vedotin(BV) combined with chemotherapy in the treatment of malignant lymphoma. Methods We collected the data of 32 lymphoma patients with CD30-positive status, including 14 cases of Hodgkin's lymphomas, 2 cases of diffuse large B-cell lymphomas, and 16 cases of mature T/NK cell lymphomas. Chemotherapy combined with BV was administered to all patients for a minimum of two cycles. The efficacy of the treatment was evaluated according to Lugano criteria every two cycles. Results Complete response rate and overall response rate after four cycles of treatment were 22% and 50%, respectively. Sixteen cases (50.0%) had grades 1 and 2 toxicity, and 16 cases (50.0%) had grade 3 toxicity or higher. The most common adverse events were neutropenia (50.0%), pneumonia (46.9%), and anemia (43.8%). The most common grade 3 or higher adverse events were pneumonia (18.8%) and febrile neutropenia (12.5%). Four patients discontinued brentuximab vedotin because of severe adverse events. Conclusion BV is effective in treating relapsed and refractory CD30- positive Hodgkin's lymphoma and peripheral T-cell lymphoma, and its overall safety is acceptable.