Aim To investigate the mechanisms of Chaijin JieYu Anshen formula modulating the depres-sive behaviors and the synaptic plasticity of hippocam-pal neurons in insomnia-concomitant depression rats based on the histone deacetylase 5(HDAC5)/myocyte enhancer factor 2C(MEF2C)pathway.Methods A rat model of insomnia-concomitant depression was es-tablished by PCPA injection combined with chronic un-predictable mild stress(CUMS),and the experiment was divided into the control group,the model group,the high,medium and low dose group of Chaijin JieYu Anshen formula,and the positive drug group.The de-pression of rats was evaluated by sugar-water prefer-ence test,open field test and morris water maze.The levels of 5-hydroxytryptamine(5-HT)and dopamine(DA)in serum were measured by enzyme linked im-munosorbent assay(ELISA).The pathological damage of hippocampal neurons was observed by HE staining and Nissl staining.The damage of dendritic spines of hippocampal neurons was observed by Golgi staining,and the levels of HDAC5,MEF2C,postsynaptic densi-ty-95(PSD-95)and synaptophysin 1(SYN1)in hip-pocampus were measured by Western blot,immunohis-tochemistry and immunofluorescence.Results Com-pared with the model group,the Chaijin JieYu Anshen formula could increase the sugar-water preference rate of the model rats,reduce the immobility time in the open field experiment,increase the total activity dis-tance,shorten the evasion latency in the localization navigation experiment,and prolong the residence time in the quadrant where the platform was located in the space exploration experiment(P＜0.05,P＜0.01).Moreover,the Chaijin JieYu Anshen formula improved the hippocampal neuron and dendritic spine damage and increase the dendritic branch length and dendritic spine density of hippocampal neurons(P＜0.01,P＜0.01),restore the serum levels of 5-HT and DA in insomnia-concomitant depression rats(P＜0.05,P＜0.01),down-regulate the HDAC5 protein,and up-regulate the expression of MEF2C,PSD-95,and SYN1 protein(P＜0.05,P＜0.01 or P＜0.001).Conclusions Chaijin JieYu Anshen formula may alle-viate the depression-like behavior of model rats by re-ducing the expression of HDAC5 protein,thus deregu-lating the inhibition of transcription factor MEF2C,promoting the expression of PSD-95 and SNY1 protein,and exerting a protective effect on hippocampal neurons and synapses.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

OBJECTIVE: To analyze the distribution and drug resistance of pathogens in oral mucositis associated with chemotherapy in hospitalized patients with malignant hematopathy, so as to provide scientific evidences for rational selection of antibiotics and infection prevention and control. METHODS: From July 2020 to June 2022, 167 patients with malignant hematopathy were treated with chemical drugs in the Department of Hematology, Hainan Hospital, and secretions from oral mucosal infected wounds were collected. VITEK2 COMPECT automatic microbial identification system (BioMerieux, France) and bacterial susceptibility card (BioMerieux) were used for bacterial identification and drug susceptibility tests. RESULTS: A total of 352 strains of pathogens were isolated from 167 patients, among which 220 strains of Gram-positive bacteria, 118 strains of Gram-negative bacteria and 14 strains of fungi, accounted for 62.50%, 33.52% and 3.98%, respectively. The Gram-positive bacteria was mainly Staphylococcus and Streptococcus, while Gram-negative bacteria was mainly Klebsiella and Proteus. The resistance of main Gram-positive bacteria to vancomycin, ciprofloxacin and gentamicin was low, and the resistance to penicillin, cefuroxime, ampicillin, cefotaxime, erythromycin and levofloxacin was high. The main Gram-negative bacteria had low resistance to gentamicin, imipenem and penicillin, but high resistance to levofloxacin, cefotaxime, cefuroxime, ampicillin and vancomycin. The clinical data of oral mucositis patients with oral ulcer (severe) and without oral ulcer (mild) were compared, and it was found that there were statistically significant differences in poor oral hygiene, diabetes, sleep duration less than 8 hours per night between two groups (P<0.05). CONCLUSION Gram-positive bacteria is the main pathogen of oral mucositis in patients with malignant hematopathy after chemotherapy. It is sensitive to glycopeptide antibiotics and aminoglycosides antibiotics. Poor oral hygiene, diabetes and sleep duration less than 8 hours per night are risk factors for oral mucositis with oral ulcer (severe).
Humans ; Vancomycin/therapeutic use* ; Cefuroxime ; Levofloxacin ; Oral Ulcer/drug therapy* ; Drug Resistance, Bacterial ; Anti-Bacterial Agents/adverse effects* ; Ampicillin ; Penicillins ; Cefotaxime ; Gram-Positive Bacteria ; Gram-Negative Bacteria ; Gentamicins ; Stomatitis/drug therapy*

Aim To explore the protective effect of Zishen Huoxue Prescription on OGD/R-induced primary hippocampal neuron damage in rats and the possible mechanism. Methods After the isolated primary hippocampal neurons were identified by immunofluorescence, OGD/R induced neuronal damage, and the changes of autophagic flux at different re-oxygenation time were observed by confocal laser scanning microscopy. After OGD/R-induced primary hippocampal neurons were intervened with serum containing Zishen Huoxue Prescription, cell viability was detected by CCK-8, cell apoptosis was detected by flow cytometry, autophagosomes were detected by transmission electron microscopy, and autophagy-related protein expressions were detected by Western blot. Results 10% Zishen Huoxue Prescription-containing serum could significantly improve cell viability and reduce the proportion of cell apoptosis, increase the number of autophagosomes in neurons, and up-regulate the expression of autophagy-related protein PINK1, Parkin, and pATG16L1. Conclusions Zishen Huoxue Prescription can effectively resist OGD/R-induced apoptosis of primary hippocampal neurons in rats, and its effect may be related to the regulation of PINK1-Parkin pathway to promote mitophagy.

Aim To investigate the role of FKBP38 in inhibiting apoptosis in a rotenone-induced Parkinson's disease(PD)cell model. Methods In vivo experiments:MPTP-induced PD in vivo models were constructed,and the expressions of α-synuclein,TH and FKBP38 in brains of PD mice were detected. In vitro experiments:Dopaminergic neuron MN9D cells were stimulated with rotenone to construct an in vitro model of PD; Western blot was used to detect the expression levels of α-synuclein,TH,Tom20 and FKBP38 in PD in vitro model; FKBP38 lentivirus was transferred into MN9D cells to construct stable overexpression and FKBP38 knockdown cell lines; CCK-8 assay was used to detect the cell viability of FKBP38 overexpression and knockdown cells stimulated by rotenone; Western blot was used to detect anti-apoptotic protein Bcl-2 and apoptosis protein in PD cell model expression levels of Bax. Results The expression level of FKBP38 was significantly down-regulated in both in vitro and in vivo models of PD(P<0.01). Knockdown of FKBP38 aggravated the decline of dopaminergic neuron cell viability caused by rotenone(P<0.05),while overexpression of FKBP38 significantly ameliorated the decline of dopaminergic neuron cell viability caused by rotenone(P<0.05). Western blot results showed that overexpression of FKBP38 could significantly up-regulate the expression level of anti-apoptotic protein Bcl-2 and increase the ratio of Bcl-2/Bax in PD dopaminergic neurons(P<0.05). Conclusion In the PD cell model regulation of FKBP38 can improve the apoptosis of dopaminergic neurons.

Aim To study the inhibitory effect of attenuated salmonella SGN1, overexpressing methioninase, on nasopharyngeal carcinoma (NPC) and the underlying mechanism. Methods The cell proliferation, cell cycle, cell apoptosis, clony formation and migration a-bility of 5-8F, HNE-2, CNE-2 cells were measured u-sing flow cytometry assay, clone formation assay, and wound assay after the methionine restriction treatment. 5-8F, HNE-2, CNE-2 cells were infected with SGN1 at the multiplicity of infection (MOI) of 1: 100 for 5 hours, followed with the measurement of cell growth. A xenograft model was constructed by subcutaneous injection of 5-8F cells in mice to observe the inhibitory effect of SGN1 on nasopharyngeal carcinoma. Results Compared with the control group, methionine restriction significantly inhibited the proliferation, migration ability, and clone formation of nasopharyngeal carcinoma cells and blocked the G

A study was conducted on rural women of childbearing age aged 20-49 who underwent the National Free Preconception Health Examination Project (NFPHEP)in Yunnan Province from 2013 to 2019. Descriptive analysis was conducted to determine the negative rate of IgG antibodies against the rubella virus and its differences among various socio-demographic characteristics. Among the 1 511 203 study subjects, the negative rate of IgG antibodies against the rubella virus was 24.36%. Only 2.64% of the population had received rubella virus vaccine. The negative rate of IgG antibodies among rural childbearing-age women in the preconception period in Yunnan Province decreased with age and educational level (P_trend<0.001). The negative rate of IgG antibodies in ethnic minority women of childbearing age in the preconception period (25.19%) was higher than that of Han women (23.88%). Among the 22 ethnic groups with over 1 000 participants, the negative rates of IgG antibodies in women of childbearing age from the Blang (32.85%), Bouyei (31.03%), Zhuang (31.01%), and Miao (30.70%) ethnic groups were higher than those of women from other ethnic groups. Among the 16 states (cities) in Yunnan Province, the negative rate of IgG antibodies in pregnant women of childbearing age in Wenshan Zhuang and Miao Autonomous Prefecture (38.06%) and Lincang City (32.63%) was higher than that in other states (cities). The negative rate of serum IgG antibodies in women who reported having received rubella virus vaccine (18.60%) was lower than that in other non-vaccinated populations (24.52%). The proportion of rural women of childbearing age in Yunnan Province who were susceptible to the rubella virus before pregnancy was still high. It is necessary to promote rubella vaccination among people susceptible to rubella, especially pregnant women, to prevent rubella virus infection and reduce the incidence rate and disease burden of rubella people.
Pregnancy ; Female ; Humans ; Rubella virus ; Immunoglobulin G ; Ethnicity ; Minority Groups ; China ; Rubella/prevention & control* ; Antigens, Viral ; Vaccines

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.
Mice ; Animals ; Gyrus Cinguli/physiology* ; Pruritus/pathology* ; Mesencephalon ; Cerebral Cortex/pathology* ; Neurons/pathology*

Influenza is an acute respiratory infectious disease caused by influenza virus. Pregnancy is associated with physiologic and immunological changes that may increase the risk for influenza virus infection and influenza-related complications. Influenza vaccination is the most effective way to prevent influenza virus infection. WHO and many countries have classified pregnant women as a priority population for influenza vaccination, however, there are still many challenges for promoting influenza vaccination in pregnant women in China, influenza vaccination coverage in pregnant women remains low and some influenza vaccine package inserts list pregnancy as an absolute contraindication. In this paper, we summarize the research progress in the effects of influenza infection and influenza vaccination during pregnancy both at home and abroad, then discuss the strategies to promote influenza vaccination in pregnancy for the purpose of providing reference for the related research and policy development in China.
Pregnancy ; Female ; Humans ; Pregnant Women ; Influenza, Human/epidemiology* ; Pregnancy Complications, Infectious/epidemiology* ; Influenza Vaccines ; Vaccination ; Orthomyxoviridae