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Abstract Background The treatment of the displaced proximal humerus fractures (PHF) still facing a lot of unsolved problems. The aim of this study was to evaluate the clinical effect of MultiLoc nails for the treatment of PHF and present outcomes of patients with different Neer’s classification and reduction quality. Methods Adult patients with PHFs were recruited and treated with MultiLoc nail. Intraoperative data, radiographic and functional outcomes, as well as occurrence of postoperative complications were assessed. Results 48 patients met inclusion and exclusion criteria and were included in this study. The DASH Score were 32.2 ± 3.1 points at 12 months, and 37.3 ± 2.5 points at the final follow-up. The mean ASES score at 12 months and final follow-up were 74.4 ± 6.2 and 78.8 ± 5.1, respectively. The mean CM Score in all 48 patients reached 68 ± 6.4 points at the final follow-up, relative side related CM Score 75.2 ± 7.7% of contralateral extremity. The incidence rate of complications was 20.8%. Patients with fracture mal-union, adhesive capsulitis were observed but no secondary surgeries were performed. There was no significantly difference of DASH Score 12 months after surgery and at the last follow-up among patients with different Neer’s classification or reduction quality. However, functional outcomes such as ASES score and CM score were significantly influenced by severity of fracture and the quality of fracture reduction. Conclusions Our study demonstrated that MultiLoc nails is well suited for proximal humeral fractures, with satisfactory health status recovery, good radiographic results, positive clinical outcomes and low rates of complications. The treatment for four part PHF still faces great challenges. Accurate fracture reduction was an important factor for good functional result.

ABSTRACTThis study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12–46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

ObjectiveTo analyze the clinical epidemiological characteristics including clinical features, disease prognosis of pneumococcal meningitis (PM), and drug sensitivity of S. pneumoniae isolates in Chinese children.MethodsA retrospective analysis was performed on the clinical, laboratory microbiological data of 160 hospitalized children less than 15 years of age with PM from January 2019 to December 2020 in 33 tertiary hospitals in China.ResultsA total of 160 PM patients were diagnosed, including 103 males and 57 females The onset age was 15 days to 15 years old, and the median age was 1 year and 3 months. There were 137 cases (85.6%) in the 3 months to

Photodynamic Therapy (PDT) is recognized for its exceptional effectiveness as a promising cancer treatment method. However, it is noted that overexposure to the dosage and sunlight in traditional PDT can result in damage to healthy tissues, due to the low tumor selectivity of currently available photosensitizers (PSs). To address this challenge, we introduce herein a new strategy where the small molecule-targeted agent, erlotinib, is integrated into a boron dipyrromethene (BODIPY)-based PS to form conjugate 6 to enhance the precision of PDT. This conjugate demonstrates optical absorption, fluorescence emission, and singlet oxygen generation efficiency comparable to the reference compound 7, which lacks erlotinib. In vitro studies reveal that, after internalization, conjugate 6 predominantly accumulates in the lysosomes of HepG2 cells, exhibiting significant photocytotoxicity with an IC50 value of 3.01 µM. A distinct preference for HepG2 cells over HELF cells is observed with conjugate 6 but not with compound 7. In vivo experiments further confirm that conjugate 6 has a specific affinity for tumor tissues, and the combination treatment of conjugate 6 with laser illumination can effectively eradicate H22 tumors in mice with outstanding biosafety. This study presents a novel and potential PS for achieving precise PDT against cancer.

Organic semiconductor materials featuring lightweight, and flexibility may play a significant role in various future applications, such as foldable displays, wearable devices, and artificial skin. For developing high-performance organic devices, organic crystals are highly desired, while a remaining fundamental issue is their contact problem. Here, we have grown a high-quality rubrene single crystal by utilizing a simple in-air sublimation technique. The contact characteristics (barrier height and contact resistance) are detail-studied by resist-free transfer electrodes (Au metal or graphene/Au). The Schottky barrier of the rubrene/graphene interface is lower and can be also modulated by gate bias, which is confirmed by spatial photocurrent mapping. Finally, we demonstrated the zero-bias photocurrent imaging application by constructing the asymmetrical device employing different electrode contacts. Our work would be of significance for studying the contact issue of organic crystals and wireless imaging.

Abstract Background Oxidative stress mediated by hyperglycemia damages cell-reparative processes such as mitophagy. Down-regulation of mitophagy is considered to be a susceptible factor for diabetes mellitus (DM) and its complications. However, the role of mitophagy in DM-associated periodontitis has not been fully elucidated. Apoptosis of human gingival epithelial cells (hGECs) is one of the representative events of DM-associated periodontitis. Thus, this study aimed to investigate PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy activated in the process of high glucose (HG)-induced hGECs apoptosis. Methods For dose–response studies, hGECs were incubated in different concentrations of glucose (5.5, 15, 25, and 50 mmol/L) for 48 h. Then, hGECs were challenged with 25 mmol/L glucose for 12 h and 48 h, respectively. Apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL), caspase 9 and mitochondrial membrane potential (MMP). Subsequently, autophagy was evaluated by estimating P62, LC3 II mRNA levels, LC3 fluorescent puncta and LC3-II/I ratio. Meanwhile, the involvement of PINK1-mediated mitophagy was assessed by qRT-PCR, western blotting and immunofluorescence. Finally, hGECs were transfected with shPINK1 and analyzed by MMP, caspase 9 and annexin V-FITC apoptosis. Results The number of TUNEL-positive cells and caspase 9 protein were significantly increased in cells challenged with HG (25 mmol/L) for 48 h (HG 48 h). MMP was impaired both at HG 12 h and HG 48 h, but the degree of depolarization was more serious at HG 48 h. The autophagy improved as the amount of LC3 II increased and p62 decreased in HG 12 h. During this process, HG 12 h treatment induced PINK1-mediated mitophagy. PINK1 silencing with HG 12 h resulted in MMP depolarization and cell apoptosis. Conclusions These results suggested that loss of the PINK1 gene may cause mitochondrial dysfunction and increase sensitivity to HG-induced apoptosis of hGECs at the early stage. PINK1 mediated mitophagy attenuates early apoptosis of gingival epithelial cells induced by high glucose.

ObjectiveThis study aimed to explore the impact of the sperm DNA fragmentation index (DFI) on the clinical outcomes in women undergoing artificial insemination by husband intrauterine insemination (AIH-IUI).MethodsIn this retrospective study, the value of sperm DFI was detected by sperm chromatin structure assay (SCSA) in a semen analysis collected before fertility treatment (basal DFI) in 1,500 IUI cycles at the infertility clinic of Northern Jiangsu People’s Hospital Reproductive Medicine Center from Jan 2016 to April 2021. Receiver operating characteristic (ROC) curves were used to calculate the cut-off value for the clinical outcomes of IUI, including the biochemical pregnancy rate, clinical pregnancy rate, delivery rate, and live birth rate, and multivariate logistic regression was conducted to analyse the risk factors for clinical outcomes after IUI.ResultIn 1,500 IUI cycles, the results showed that there were no statistically significant differences between the normal DFI group and the abnormal DFI group in biochemical pregnancy rate (14.41% vs. 11.3%, P = 0.386), clinical pregnancy rate (12.9% vs. 10.5%, P = 0.433), delivery rate (11.0% vs. 8.9%, P = 0.456), live birth rate (10.9% vs. 8.9%, P = 0.484) or pregnancy loss rate (14.6% vs. 15.4%, P = 1.000).ConclusionSperm DFI alone may have limited predictive power for IUI clinical outcomes.

PurposeTo evaluate the effect of elevated sperm DNA fragmentation index (DFI) on fresh and frozen embryo transfer cycles.MethodsA retrospective study was performed with 549 fresh embryo transfer cycles and 1340 frozen embryo transfer cycles after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) from 2016 to 2021.ResultsThe statistical results of 549 fresh embryo transfer cycles showed that the delivery rate in the normal sperm DFI group (43.9% vs. 27.1%, P = 0.014) was significantly higher than that in the abnormal sperm DFI group, and there were no significant differences in the biochemical pregnancy rate (59.0% vs. 50.8%, P = 0.232), clinical pregnancy rate (53.1% vs. 40.7%, P = 0.072), or miscarriage rate (17.3% vs. 33.3%, P = 0.098) between the two groups. The results of 1340 frozen embryo transfer cycles showed that the biochemical pregnancy rate (57.9% vs. 45.6%, P = 0.006) and clinical pregnancy rate (50.3% vs. 40.7%, P = 0.027) in the normal sperm DFI group were significantly higher than those in the abnormal sperm DFI group. The delivery rate (40.9% vs. 33.3%, P = 0.074) and miscarriage rate (18.6% vs. 18.0%, P = 0.919) were not significantly different between the two groups.ConclusionThe increase of sperm DFI significantly reduced the delivery rate of fresh embryo transfer cycles and the biochemical pregnancy rate and clinical pregnancy rate of frozen embryo transfer cycles.

Abstract Background Pediatric bacterial meningitis (PBM) remains a devastating disease that causes substantial neurological morbidity and mortality worldwide. However, there are few large-scale studies on the pathogens causing PBM and their antimicrobial resistance (AMR) patterns in China. The present multicenter survey summarized the features of the etiological agents of PBM and characterized their AMR patterns. Methods Patients diagnosed with PBM were enrolled retrospectively at 13 children’s hospitals in China from 2016 to 2018 and were screened based on a review of cerebrospinal fluid (CSF) microbiology results. Demographic characteristics, the causative organisms and their AMR patterns were systematically analyzed. Results Overall, 1193 CSF bacterial isolates from 1142 patients with PBM were obtained. The three leading pathogens causing PBM were Staphylococcus epidermidis (16.5%), Escherichia coli (12.4%) and Streptococcus pneumoniae (10.6%). In infants under 3 months of age, the top 3 pathogens were E. coli (116/523; 22.2%), Enterococcus faecium (75/523; 14.3%), and S. epidermidis (57/523; 10.9%). However, in children more than 3 months of age, the top 3 pathogens were S. epidermidis (140/670; 20.9%), S. pneumoniae (117/670; 17.5%), and Staphylococcus hominis (57/670; 8.5%). More than 93.0% of E. coli isolates were sensitive to cefoxitin, piperacillin/tazobactam, cefoperazone/sulbactam, amikacin and carbapenems, and the resistance rates to ceftriaxone, cefotaxime and ceftazidime were 49.4%, 49.2% and 26.4%, respectively. From 2016 to 2018, the proportion of methicillin-resistant coagulase-negative Staphylococcus isolates (MRCoNS) declined from 80.5 to 72.3%, and the frequency of penicillin-resistant S. pneumoniae isolates increased from 75.0 to 87.5%. The proportion of extended-spectrum β-lactamase (ESBL)-producing E. coli fluctuated between 44.4 and 49.2%, and the detection rate of ESBL production in Klebsiella pneumoniae ranged from 55.6 to 88.9%. The resistance of E. coli strains to carbapenems was 5.0%, but the overall prevalence of carbapenem-resistant K. pneumoniae (CRKP) was high (54.5%). Conclusions S. epidermidis, E. coli and S. pneumoniae were the predominant pathogens causing PBM in Chinese patients. The distribution of PBM causative organisms varied by age. The resistance of CoNS to methicillin and the high incidence of ESBL production among E. coli and K. pneumoniae isolates were concerning. CRKP poses a critical challenge for the treatment of PBM.

After the first national-scale outbreak of Hand, foot, and mouth disease (HFMD) in China, a national surveillance network was established. Here we described the epidemiology and pathogenic profile of HFMD and the impact of EV-A71 vaccination on pathogen spectrum of enteroviruses in the southeastern Chinese city of Nanchang during 2010–2019. A total of 7,951 HFMD cases from sentinel hospitals were included, of which 4,800 EV-positive cases (60.4%) were identified by real-time RT-PCR. During 2010–2012, enterovirus 71 (EV-A71) was the main causative agent of HFMD, causing 63.1% of cases, followed by 19.3% cases associated with coxsackievirus A16 (CV-A16). Since 2013, the proportion of other enteroviruses has increased dramatically, with the sub genotype D3 strain of Coxsackievirus A6 (CV-A6) replacing the dominance of EV-A71. These genetically diverse native strains of CV-A6 have co-transmitted and co-evolved in Nanchang. Unlike EV-A71 and CV-A16, most CV-A6 infections were concentrated in autumn and winter. The incidence of EV-A71 infection negatively correlated with EV-A71 vaccination (r = −0.990, p = 0.01). And severe cases sharply declined as the promotion of EV-A71 vaccines. After 2-year implementation of EV-A71 vaccination, EV-A71 is no longer detected from the reported HFMD cases in Nanchang. In conclusion, EV-A71 vaccination changed the pattern of HFMD epidemic, and CV-A6 replaced the dominance of EV-A71 over time.

Background: Antimicrobial resistance is a significant clinical problem in pediatric practice in China. Surveillance of antibiotic use is one of the cornerstones to assess the quality of antibiotic use and plan and assess the impact of antibiotic stewardship interventions.Methods: We carried out quarterly point prevalence surveys referring to WHO Methodology of Point Prevalence Survey in 16 Chinese general and children’s hospitals in 2019 to assess antibiotic use in pediatric inpatients based on the WHO AWaRe metrics and to detect potential problem areas. Data were retrieved via the hospital information systems on the second Monday of March, June, September and December. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions and ward types according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) Classification.Results: A total of 22,327 hospitalized children were sampled, of which 14,757 (66.1%) were prescribed ≥1 antibiotic. Among the 3,936 sampled neonates (≤1 month), 59.2% (n = 2,331) were prescribed ≥1 antibiotic. A high percentage of combination antibiotic therapy was observed in PICUs (78.5%), pediatric medical wards (68.1%) and surgical wards (65.2%). For hospitalized children prescribed ≥1 antibiotic, the most common diagnosis on admission were lower respiratory tract infections (43.2%, n = 6,379). WHO Watch group antibiotics accounted for 70.4% of prescriptions (n = 12,915). The most prescribed antibiotic ATC classes were third-generation cephalosporins (41.9%, n = 7,679), followed by penicillins/β-lactamase inhibitors (16.1%, n = 2,962), macrolides (12.1%, n = 2,214) and carbapenems (7.7%, n = 1,331).Conclusion: Based on these data, overuse of broad-spectrum Watch group antibiotics is common in Chinese pediatric inpatients. Specific interventions in the context of the national antimicrobial stewardship framework should aim to reduce the use of Watch antibiotics and routine surveillance of antibiotic use using WHO AWaRe metrics should be implemented.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease characterized by persistent anovulation and hyperandrogenism, affecting approximately 8–10% of women of childbearing age and occupying an important position in the etiology of infertility. There is increasing evidence that long non-coding RNAs (lncRNAs) are involved in the development of PCOS, but the potential regulatory mechanism is still unclear. This study performed high-throughput lncRNA sequencing of follicular fluid exosomes in non-PCOS infertility patients and PCOS infertility patients. The sequencing results led to the identification of 1,253 upregulated and 613 downregulated lncRNAs from a total of 1,866 detected candidates. There was no significant difference between the PCOS patients and non-PCOS patients in body mass index (BMI) or the fasting blood glucose (FBG) level. However, luteinizing hormone (LH), estradiol (E2), testosterone (T), serum prolactin (PRL), and anti-Mullerian hormone (AMH) levels were clearly upregulated in PCOS patients compared to those in non-PCOS patients. There was also an increase in LH/FSH (>2) in the PCOS patients. Functional analysis showed pathways related to endocytosis, the Hippo, the MAPK, and HTLV-1 infection. These results suggest that lncRNAs may play an important role in the pathogenesis of PCOS and may be potential targets for the diagnosis and treatment of PCOS.

Myzus persicae (Sulzer), commonly known as the green peach aphid, is a notorious pest that causes substantial losses to a range of crops and can transmit several plant viruses, including potato virus Y (PVY). Chemical insecticides provide only partial control of this pest and their use is not environmentally sustainable. In recent years, many genes related to growth, development, and reproduction have been used as targets for pest control. These include Gustavus (Gus), a highly conserved gene that has been reported to play an essential part in the genesis of germline cells and, hence, in fecundity in the model insect Drosophila melanogaster. We hypothesized that the Gustavus (Gus) gene was a potential target that could be used to regulate the M. persicae population. In this study, we report the first investigation of an ortholog of Gus in M. persicae, designated MpGus, and describe its role in the fecundity of this insect. First, we identified the MpGus mRNA sequence in the M. persicae transcriptome database, verified its identity with reverse transcription-polymerase chain reaction (RT-PCR), and then evaluated the transcription levels of MpGus in M. persicae nymphs of different instars and tissues with real-time quantitative PCR (RT-qPCR). To investigate its role in regulating the fecundity of M. persicae, we used RNA interference (RNAi) to silence the expression of MpGus in adult insects; this resulted in a significant reduction in the number of embryos (50.6%, P < 0.01) and newborn nymphs (55.7%, P < 0.01) in the treated aphids compared with controls. Interestingly, MpGus was also significantly downregulated in aphids fed on tobacco plants that had been pre-infected with PVYN, concomitant with a significant reduction (34.1%, P < 0.01) in M. persicae fecundity. Collectively, these data highlight the important role of MpGus in regulating fecundity in M. persicae and indicate that MpGus is a promising RNAi target gene for control of this pest species.

Abstract Coptidis Rhizoma binds to the membrane receptors on hPDLSC/CMC, and the active ingredient Berberine (BER) that can be extracted from it may promote the proliferation and osteogenesis of periodontal ligament stem cells (hPDLSC). The membrane receptor that binds with BER on the cell surface of hPDLSC, the mechanism of direct interaction between BER and hPDLSC, and the related signal pathway are not yet clear. In this research, EGFR was screened as the affinity membrane receptor between BER and hPDLSC, through retention on CMC, competition with BER and by using a molecular docking simulation score. At the same time, the MAPK PCR Array was selected to screen the target genes that changed when hPDLSC was simulated by BER. In conclusion, BER may bind to EGFR on the cell membrane of hPDLSC so the intracellular ERK signalling pathways activate, and nuclear-related genes of FOS change, resulting in the effect of osteogenesis on PDLSC.

A cyclophosphazene derivative containing multiple cyano groups, denoted as hexa(4-cyanophenoxy)cyclotriphosphazene (CN-CP), was synthesized by a one-step nucleophilic substitution reaction for a phosphorus-nitrogen flame retardant. To meet the strict requirement of safe and environment-protective insulation materials, a series of composites based on low-density polyethylene-poly(ethylene-co-vinyl acetate) containing CN-CP/Mg(OH)2/Al(OH)3 organic-inorganic synergistic flame retardants was fabricated. High-energy electron beam irradiation was subsequently applied to obtain a halogen-free flame-retardant crosslinked system. The relationship between crosslinking degree and irradiation dose was studied, and crosslinking degrees ranging within 63–85% were obtained under 100–190 kGy. Furthermore, the effects of CN-CP filler and irradiation dose on the properties of the composites were carefully investigated. The maximum tensile stress and limiting oxygen index values of most composites irradiated by EB were more than 15 MPa and 28%. Results revealed that the obtained materials had excellent thermal and mechanical, flame-retardant, and insulation properties, thereby suggesting their promising prospects for wire and cable applications.

Background/Aims: Periodic mechanical stress could significantly promote chondrocyte proliferation and matrix synthesis. However, the mechanisms underlying the ability of chondrocyte detecting and responding to periodic mechanical stimuli have not been well delineated. Methods: Quantitative proteomic analysis was performed to construct the differently expressed proteome profiles of chondrocyte under pressure. Then a combination of Western blot, quantitative real-time PCR, lentiviral vector and histological methods were used to confirm the proteomic results and investigate the mechanoseing mechanism. Results: Growth factor receptor-bound protein 2 (Grb2), a component of integrin adhesome, was found a 1.49-fold increase in dynamic stress group. This process was mediated through integrin β1, leading to increased phosphorylation of focal adhesion kinase (FAK) and extracellular signal–regulated kinase 1/2 (ERK1/2) respectively and then produce the corresponding biological effects. Conclusion: This was the first time to demonstrate Grb2 has such an important role in periodic mechanotransduction, and the proteomic data could facilitate the further investigation of chondrocytes mechanosensing.

Mid-infrared pulsed sources are technologically important for sensing and spectroscopy but their implementation is challenging due to the lack of a tuneable optical switch. Here, the authors address this limitation by engineering the band structure of an emerging Dirac semimetal, Cd3As2.

WRKY proteins are a large group of plant transcription factors that are involved in various biological processes, including biotic and abiotic stress responses, hormone response, plant development, and metabolism. WRKY proteins have been identified in several plants, but only a few have been identified in Capsicum annuum. Here, we identified a total of 62 WRKY genes in the latest pepper genome. These genes were classified into three groups (Groups 1-3) based on the structural features of their proteins. The structures of the encoded proteins, evolution, and expression under normal growth conditions were analyzed and 35 putative miRNA target sites were predicted in 20 CaWRKY genes. Moreover, the response to cold or CMV treatments of selected WRKY genes were examined to validate the roles under stresses. And alternative splicing (AS) events of some CaWRKYs were also identified under CMV infection. Promoter analysis confirmed that CaWRKY genes are involved in growth, development, and biotic or abiotic stress responses in hot pepper. The comprehensive analysis provides fundamental information for better understanding of the signaling pathways involved in the WRKY-mediated regulation of developmental processes, as well as biotic and abiotic stress responses.

Background/Aims: Periodic mechanical stress activates integrin β1-initiated signal pathways to promote chondrocyte proliferation and matrix synthesis. Integrin β1 overexpression has been demonstrated to play important roles in improving the activities and functions of several non-chondrocytic cell types. Therefore, in the current study, we evaluated the effects of integrin β1 up-regulation on periodic mechanical stress-induced chondrocyte proliferation, matrix synthesis and ERK1/2 phosphorylation in chondrocyte monolayer culture, and evaluated the quality of tissue-engineered cartilage constructed in vitro under periodic mechanical stress combined with integrin β1 up-regulation. Methods and Results: Our results revealed that under periodic mechanical stress, pre-treatment with integrin β1-wild type vector significantly enhanced chondrocyte proliferation and matrix synthesis and promoted ERK1/2 phosphorylation in comparison to mock transfectants. Furthermore, when chondrocytes were seeded in PLGA scaffolds, more accumulated GAG and type II collagen tissue were detected after Lv-integrin β1 transfection compared with sham controls exposed to periodic mechanical stress. In contrast, in the Lv-shRNA-integrin β1 group, the opposite results were observed. Conclusion: Our findings collectively suggest that in addition to periodic mechanical stress, integrin β1 up-regulation in chondrocytes could further improve the quality of tissue-engineered cartilage.

Intracellular calcium concentration ([Ca(2+)]i) plays an important role in regulating most cellular processes, including apoptosis and survival, but its alterations are different and complicated under diverse conditions. In this study, we focused on the [Ca(2+)]i and its control mechanisms in process of hydrogen peroxide (H2O2)-induced apoptosis of primary cultured Sprague-Dawley (SD) rat retinal cells and 17β-estradiol (βE2) anti-apoptosis. Fluo-3AM was used as a Ca(2+) indicator to detect [Ca(2+)]i through fluorescence-activated cell sorting (FACS), cell viability was assayed using MTT assay, and apoptosis was marked by Hoechst 33342 and annexin V/Propidium Iodide staining. Besides, PI3K activity was detected by Western blotting. Results showed: a) 100 μM H2O2-induced retinal cell apoptosis occurred at 4 h after H2O2 stress and increased in a time-dependent manner, but [Ca(2+)]i increased earlier at 2 h, sustained to 12 h, and then recovered at 24 h after H2O2 stress; b) 10 μM βE2 treatment for 0.5-24 hrs increased cell viability by transiently increasing [Ca(2+)]i, which appeared only at 0.5 h after βE2 application; c) increased [Ca(2+)]i under 100 µM H2O2 treatment for 2 hrs or 10 µM βE2 treatment for 0.5 hrs was, at least partly, due to extracellular Ca(2+) stores; d) importantly, the transiently increased [Ca(2+)]i induced by 10 µM βE2 treatment for 0.5 hrs was mediated by the phosphatidylinositol-3-kinase (PI3K) and gated by the L-type voltage-gated Ca(2+) channels (L-VGCC), but the increased [Ca(2+)]i induced by 100 µM H2O2 treatment for 2 hrs was not affected; and e) pretreatment with 10 µM βE2 for 0.5 hrs effectively protected retinal cells from apoptosis induced by 100 µM H2O2, which was also associated with its transient [Ca(2+)]i increase through L-VGCC and PI3K pathway. These findings will lead to better understanding of the mechanisms of βE2-mediated retinal protection and to exploration of the novel therapeutic strategies for retina degeneration.

The diabetic peripheral neuropathy pain model was constructed after 95 Sprague Dawley rats had been randomly divided among blank reference and model groups. Aescin low-dose group (0.5 mg/kg), aescin medium-dose group (1.0 mg/kg), aescin high-dose group (1.5 mg/kg), and positive control group (0.25 mg/ kg mecobalamin) were then randomly assigned to the simulation group following successful modeling. At the conclusion of the study, the mean sciatic nerve conduction velocity was determined, blood glucose in addition to the amount of inflammatory factors tumor necrosis factor-alpha, interleukin-6, and interleukin-1 were determined, and sciatic nerve cells from mice in all groups were collected for Western blot to identify the protein levels of high mobility group box 1 and receptor for advanced glycation end products. The mean sciatic nerve conduction velocity of the medium and high-dose groups of aescin was higher than those of the model control (p<0.05); rat blood glucose content, the contents of inflammatory factors interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha as well as the protein expression of high mobility group box 1 and receptor for advanced glycation end products in sciatic nerve tissue were lower and the body mass was higher than that of the model control group (p<0.05). Comparing the high-dose aescin group as well as the positive control group, there had been no discernible change in the aforementioned indices (p>0.05). Aescin is able to effectively improve the inflammatory response in the body by regulating high mobility group box 1-receptor for advanced glycation end products levels and slow down diabetic peripheral neuropathy caused by the inflammatory response. [ABSTRACT FROM AUTHOR]