Combining bioinformatics, network pharmacology and artificial intelligence to predict the target genes of S-ketamine for treating major depressive disorder.

BACKGROUND: Ketamine has received attention owing to its rapid and long-lasting antidepressant effects; however, its clinical application is restricted by its addictiveness and adverse effects. S-ketamine, which is the S-enantiomer of ketamine, is considered safer and better tolerated by patients than ketamine. AIMS: This study aimed to identify the key gene targets and potential signalling pathways associated with the mechanism of S-ketamine in major depressive disorder (MDD) treatment. METHODS: The GSE98793 dataset was extracted from the Gene Expression Omnibus database, and differentially expressed genes were identified in blood samples from patients with MDD and healthy individuals. The hub genes among the differentially expressed genes were identified and enrichment analysis was performed. The therapeutic targets and related signalling pathways of S-ketamine in MDD treatment were analysed. The 3D structures of the target proteins were predicted using AlphaFold2, and molecular docking was performed to verify whether S-ketamine could be successfully docked to the predicted targets. A quantitative polymerase chain reaction was performed to determine the effect of ketamine on the screened targets. Among 228 target genes annotated using pharmacophore target gene analysis, 3 genes were identified and 2 therapeutic signalling pathways were discovered. RESULTS: S-ketamine exerts downregulatory effects on TGM2 and HSP90AB1 expression but exerts an up-regulatory effect on ADORA3 expression. The protein structures of the therapeutic targets were successfully predicted using AlphaFold2. CONCLUSIONS: S-ketamine may alleviate depression by targeting specific genes, including TGM2, HSP90AB1 and ADORA3, as well as signalling pathways, including the gonadotropin-releasing hormone and relaxin signalling pathways.

Follicular fluid HD-sevs-mir-128-3p is a key molecule in regulating bovine granulosa cells autophagy.

Follicular fluid (FF) is rich in extracellular vesicles (EVs). EVs carries a variety of miRNA involved in regulating follicular development, the function of cells in follicles, primordial follicular formation, follicular recruitment and selection, follicular atresia, oocyte communication, granulosa cells (GCs) function and luteinization and other biological processes of follicular development. Previous studies in our laboratory have shown that bovine follicular fluid (bFF) high density-small extracellular vesicles (HD-sEVs)-miRNA was enriched in autophagy-related pathways. However, the mechanism of bFF EVs carrying miRNA regulating GCs autophagy is not clear. Thus, this study carried out a series of studies on the previous HD-sEVs sequencing data and miR-128-3p contained in bFF HD-sEVs. A total of 38 differentially expressed genes were detected by RNA-Seq after overexpression of miR-128-3p in bovine GCs (bGCs). Through cell transfection, Western blot (WB) and Immunofluorescence (IF), it was proved that overexpression of miR-128-3p could promote the expression of LC3 (microtubule-associated protein I light chain 3), inhibit p62, promote the number of autophagosome, promote the formation of autophagy lysosome and autophagy flow, and activate bGCs autophagy. MiR-128-3p inhibitor significantly inhibited the expression of LC3 and monodansylcadaverine (MDC) in bGCs, and promoted the expression of autophagy substrate p62, indicating that HD-sEVs-miR-128-3p could activate bGCs autophagy. In addition, through double luciferase assay, bioinformatics analysis, WB and RT-qPCR, it was concluded that bFF HD-sEVs-miR-128-3p could target TFEB (transcription factor EB) and FoxO4 (Forkhead box O4) and activate GCs autophagy.

Allogeneic hematopoietic stem cell transplant for familial hemophagocytic lymphohistiocytosis: a case report and literature review.

Objectives: This study aims to discuss the clinical manifestations and treatment of Familial hemophagocytic lymphohistiocytosis (FHL) caused by a mutation in the UNC13D gene. Methods: A 6-year-old female child presented with unexplained febricity, splenomegaly, pancytopenia, hemophagocytic lymphohistiocytosis in bone marrow, decreased NK cell activity, soluble CD25 levels > 44000ng/ml. Genetic sequencing revealed a mutation in the UNC13D gene. Additionally, the patient experienced intermittent fever with seizures characterized by involuntary twitching of the left upper limb. Head magnetic resonance imaging (MRI) showed white matter lesions. Results: According to the HLH-2004 diagnostic criteria revised by the International Society of Histiocytosis the patient was diagnosed with FHL. Despite receiving HLH-2004 treatment, the disease relapsed. However, after a salvage allogeneic Hematopoietic Stem Cell Transplant (HSCT), febricity, abnormal blood cells, and neurological symptoms significantly improved. Conclusions: Prompt performance of allogeneic HSCT is crucial upon diagnosis of FHL, especially when neurological involvement is present.

Chromosome-level genome assembly of Odontothrips loti Haliday (Thysanoptera: Thripidae).

As the predominant pest of alfalfa, Odontothrips loti Haliday causes great damages over the major alfalfa-growing regions of China. The characteristics of strong mobility and fecundity make them develop rapidly in the field and hard to be controlled. There is a shortage of bioinformation and limited genomic resources available of O. loti for us to develop novel pest management strategies. In this study, we constructed a chromosome-level reference genome assembly of O. loti with a genome size of 346.59 Mb and scaffold N50 length of 18.52 Mb, anchored onto 16 chromosomes and contained 20128 genes, of which 93.59% were functionally annotated. The results of 99.20% complete insecta_odb10 genes in BUSCO analysis, 91.11% short reads mapped to the ref-genome, and the consistent tendency among the thrips in the distribution of gene length reflects the quality of genome. Our study provided the first report of genome for the genus Odontothrips, which offers a genomic resource for further investigations on evolution and molecular biology of O. loti, contributing to pest management.

Transplantation of Neural Stem Cells Loaded in an IGF-1 Bioactive Supramolecular Nanofiber Hydrogel for the Effective Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) leads to massive cell death, disruption, and demyelination of axons, resulting in permanent motor and sensory dysfunctions. Stem cell transplantation is a promising therapy for SCI. However, owing to the poor microenvironment that develops following SCI, the bioactivities of these grafted stem cells are limited. Cell implantation combined with biomaterial therapies is widely studied for the development of tissue engineering technology. Herein, an insulin-like growth factor-1 (IGF-1)-bioactive supramolecular nanofiber hydrogel (IGF-1 gel) is synthesized that can activate IGF-1 downstream signaling, prevent the apoptosis of neural stem cells (NSCs), improve their proliferation, and induce their differentiation into neurons and oligodendrocytes. Moreover, implantation of NSCs carried out with IGF-1 gels promotes neurite outgrowth and myelin sheath regeneration at lesion sites following SCI. In addition, IGF-1 gels can enrich extracellular vesicles (EVs) derived from NSCs or from nerve cells differentiated from these NSCs via miRNAs related to axonal regeneration and remyelination, even in an inflammatory environment. These EVs are taken up by autologous endogenous NSCs and regulate their differentiation. This study provides adequate evidence that combined treatment with NSCs and IGF-1 gels is a potential therapeutic strategy for treating SCI.

A literature review of a meta-analysis of BRAF mutations in non-small cell lung cancer.

BACKGROUND: The research on the relationship between the Braf Proto-oncogene (BRAF) mutation and lung cancer has generated conflicting findings. Nevertheless, there is an argument suggesting that assessing the BRAF status could offer benefits in terms of managing and prognosing individuals with non-small cell lung cancer (NSCLC). To present a comprehensive overview of this subject, we undertook an up-to-date meta-analysis of pertinent publications. METHODS: We conducted an extensive literature search utilizing Medical Subject Headings keywords, namely "BRAF", "mutation", "lung", "tumor", "NSCLC", and "neoplasm", across multiple databases, including PubMed, EMBASE, ISI Science Citation Index, and CNKI. For each study, we calculated and evaluated the odds ratio and confidence interval, focusing on the consistency of the eligible research. RESULTS: The meta-analysis unveiled a noteworthy correlation between BRAF mutation and lung cancer. No significant evidence was found regarding the connection between smoking and staging among individuals with BRAF mutations. Furthermore, a substantial disparity in the rate of BRAF mutations was observed between males and females. CONCLUSION: Our meta-analysis revealed a significant correlation between BRAF mutations and NSCLC. Moreover, we observed a higher incidence of BRAF lung mutations in females compared to males. Additionally, the BRAFV600E mutation was found to be more prevalent among female patients and nonsmokers.

Efficient crop straws biotreatment using the fungus Cerrena Unicolor GC.u01.

Lignin is main composition of agricultural biomass which can be decomposed through enzymatic hydrolysis by fungi. However, there are still needs to identify more efficient and effective fungal stain for biomass valorization. In this study, lignin degrading fungi from birch forest were screened for sustainable degradation of waste agricultural straws. The most effective strain was identified as Cerrena unicolor GC.u01 using 18 S rDNA gene-sequencing technology. Three different crop straws (corn stalk, rice and wheat straws) were used for the biotreatment studies. The activities of lignin degrading enzymes, laccase (Lac), cellulase and xylanase, secreted by C. unicolor were also determined. Scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analyzer (TGA) were further used to monitor the effects of the biotreatment process. The results showed that C. unicolor degraded 34.3% rice straw lignin, a percentage which was higher than other isolated strains after 15 d straw liquid fermentation. The highest Lac activity (8.396 U•mL- 1) was observed with corn stalk on the 7 d. Cellulase and xylanase activities, in the same biomass, were higher than those of wheat and rice straws after 15 d. Furthermore, SEM, FTIR and TGA analyses showed that C. unicolor pretreatment process had significant effects on corn stalk, rice and wheat straws' structures. The newly isolated stain of C. unicolor demonstrated high lignin degradation potential that can provide effective, ecofriendly means of valorizing biomass to industrial useable raw-material.

Identifying clinical risk factors correlated with addictive features of non-suicidal self-injury among a consecutive psychiatric outpatient sample of adolescents and young adults.

Non-suicidal self-injury (NSSI) is an issue primarily of concern in adolescents and young adults. Recent literature suggests that persistent, repetitive, and uncontrollable NSSI can be conceptualized as a behavioral addiction. The study aimed to examine the prevalence of NSSI with addictive features and the association of this prevalence with demographic and clinical variables using a cross-sectional and case-control design. A total of 548 outpatients (12 to 22 years old) meeting the criteria for NSSI disorder of DSM-5 were enrolled and completed clinical interviews by 4 psychiatrists. NSSI with addictive features were determined by using a single-factor structure of addictive features items in the Ottawa self-injury inventory (OSI). Current suicidality, psychiatric diagnosis, the OSI, the revised Chinese Internet Addiction Scale, the Childhood Trauma Questionnaire, and the 20-item Toronto Alexithymia Scale were collected. Binary logistic regression analyses were used to explore associations between risk factors and NSSI with addictive features. This study was conducted from April 2021 to May 2022. The mean age of participants was 15.93 (SD = 2.56) years with 418 females (76.3%), and the prevalence of addictive NSSI was 57.5% (n = 315). Subjects with addictive NSSI had a higher lifetime prevalence of nicotine and alcohol use, a higher prevalence of current internet addiction, suicidality, and alexithymia, and were more likely to have physical abuse/neglect, emotional abuse, and sexual abuse than NSSI subjects without addictive features. Among participants with NSSI, the strongest predictors of addictive features of NSSI were female (OR = 2.405, 95% CI 1.512-3.824, p < 0.0001), alcohol use (OR = 2.179, 95% CI 1.378-3.446, p = 0.001), current suicidality (OR = 3.790, 95% CI 2.351-6.109, p < 0.0001), and psysical abuse in childhood (OR = 2.470, 95% CI 1.653-3.690, p < 0.0001). Nearly 3 out of 5 patients (12-22 years old) with NSSI met the criteria of NSSI with addictive features in this psychiatric outpatients sample. Our study demonstrated the importance of the necessity to regularly assess suicide risk, and alcohol use, as well as focus more on females and subjects who had physical abuse in childhood to prevent addictive NSSI.

Promising response of dabrafenib, trametinib, and osimertinib combination therapy for concomitant BRAF and EGFR-TKI resistance mutations.

Despite the initial promise of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in effectively combating tumor growth, the majority of patients with advanced non-small cell lung cancers (NSCLCs) inevitably develop resistance to these treatments. An infrequent genetic mutation known as BRAFV600E has been identified as a contributing factor to the emergence of acquired resistance to EGFR-TKIs. Genetic alterations in BRAF, particularly V600E, contribute to resistance to osimertinib. However, a combination therapy involving osimertinib, dabrafenib (a BRAF inhibitor), and trametinib has shown effectiveness in overcoming BRAF V600E-mediated resistance in advanced lung adenocarcinoma. This treatment regimen holds promise for similar cases. In our case report, the combination of osimertinib, dabrafenib, and trametinib effectively overcame osimertinib resistance and resulted in sustained partial remission.

Syndromes and Mechanisms of Depression Induced by Second Hit in Mice / 中国实验方剂学杂志

ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.

Wenyang Jieyu Prescription Regulates Hippocampal Neural Plasticity in Depressed Mice via NLRP3/Caspase-1/IL-1β Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effects of Wenyang Jieyu prescription （WJP） on neuroinflammation and synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 （PD0） were randomized into a control group and a modeling group. Maternal separation combined with restraint stress was employed to establish the mouse model of depression. After the removal of female mice， the modeled mice were randomized into model， Wenyang prescription （5.85 g·kg-1）， Jieyu prescription （12.03 g·kg-1）， WJP （16.71 g·kg-1）， and fluoxetine （2.6 mg·kg-1） groups on the weaning day （PD21）， with 15 mice in each group. The mice were administrated with corresponding drugs mixed with the diet from PD21 to PD111. The sucrose preference test， open field test， O-maze test， and novel object recognition test were then carried out to evaluate the depression state， memory， and learning ability of the mice. Immunohistochemistry （IHC） was employed to observe the ionized calcium-binding adapter molecule-1 （Iba-1） in hippocampal microglia. High performance liquid chromatography （HPLC） was employed to measure the content of noradrenaline （NE） and epinephrine （E） in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the content of interleukin （IL）-18 and IL-1β in the hippocampus. Western blot was employed to determine the protein levels of NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， cysteine aspartate-specific protease-1 （Caspase-1）， IL-1β， synaptophysin （Syn）， and postsynaptic density 95 （PSD95）. ResultCompared with control group， the model group showed decreased sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. The microglia in the model group presented amoeba-like appearance， the Iba1 increased. Moreover， the model group showed decreased content of NE and E （P<0.01）， elevated levels of IL-1β and IL-18 （P<0.01）， down-regulated protein levels of PSD95 and Syn （P<0.05， P<0.01）， and up-regulated protein levels of NLRP3， ASC， Caspase-1， and IL-1β （P<0.05， P<0.01）. Compared with model group， WJP and fluoxetine increased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. They recovered the microglia and the Iba1 decreased. Moreover， the drugs increased the content of NE and E （P<0.05， P<0.01）， lowered the levels of IL-1β and IL-18 （P<0.01）， up-regulated the protein levels of PSD95 and Syn （P<0.01）， down-regulated the protein levels of NLRP3， ASC， Caspase-1， and IL-1β （P<0.05， P<0.01）. ConclusionWJP can treat the depressive behavior induced by maternal separation combined with restraint stress in mice， with the performance outperforming Wenyang prescription and Jieyu prescription. It may alleviate the neuroinflammation induced by microglia and improve the synaptic plasticity by regulating the NLRP3 pathway and increasing neurotransmitters in the hippocampus.

Wenyang Jieyu Prescription Regulates Hippocampal Neuron Apoptosis and Improves Synaptic Plasticity in Depressed Mice via BDNF/Akt/mTOR Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Wenyang Jieyu prescription in regulating hippocampal neuron apoptosis and improving synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 （PD0） were randomly assigned into a control group （n=10） and a modeling group （n=50）. Maternal separation combined with restraint stress was adopted to establish the mouse model of depression， and the modeled mice were randomized into model， Wenyang prescription， Jieyu prescription， Wenyang Jieyu prescription， and fluoxetine groups （n=10） on the weaning day （PD21）. From PD21 to PD111， the mice were fed with the diets mixed with corresponding medicines. The sucrose preference test， open field test， O-maze test， and novel object recognition test were then conducted to evaluate the depression， memory， and learning abilities of mice. Immunohistochemistry （IHC） was employed to measure the atomic absorbance （AA） of postsynaptic density protein 95 （PSD95） in the hippocampus. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to detect the apoptosis of hippocampal neurons. Western blot was employed to determine the protein levels of brain-derived neurotrophic factor （BDNF）， phosphorylated tyrosine kinase receptor B/tyrosine kinase receptor B （p-TrkB/TrkB）， phosphorylated protein kinase B/protein kinase B （p-Akt/Akt）， phosphorylated mammalian target of rapamycin/mammalian target of rapamycin （p-mTOR/mTOR）， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X （Bax）， cysteinyl aspartate-specific proteinase-3 （Caspase-3）， synaptophysin （Syn）， and PSD95. ResultCompared with the control group， the modeling decreased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.01）. Furthermore， it decreased the expression of PSD95， increased the neuron apoptosis in the hippocampus （P<0.01）， down-regulated the protein levels of BDNF， p-TrkB/TrkB， p-Akt/Akt， p-mTOR/mTOR， Bcl-2， PSD95， and Syn （P<0.01）， and up-regulated the protein levels of Bax and Caspase-3 （P<0.05） in the hippocampus. Compared with the model group， Wenyang Jieyu prescription and fluoxetine increased the sucrose preference rate， time spent in central zone within 5 min， total movement distance， time spent in the open arm， and cognition index （P<0.05， P<0.01）. Moreover， the drugs increased the expression of PSD95， reduced the neuron apoptosis （P<0.01）， up-regulated the protein levels of BDNF， p-TrkB/TrkB， p-Akt/Akt， p-mTOR/mTOR， Bcl-2， PSD95， and Syn （P<0.01）， and down-regulated the protein levels of Bax and Caspase-3 （P<0.01）. ConclusionWenyang Jieyu prescription outperformed Wenyang prescription and Jieyu prescription in the treatment of the depressive behavior induced by maternal separation combined with restraint stress in mice. It exerted the therapeutic effect by reducing the hippocampal neuron apoptosis and improving the synaptic plasticity via the BDNF/Akt/mTOR pathway.

Establishment of pharmaceutical care pathway based on the problems related to chemotherapy / 中国药房

OBJECTIVE To design pharmaceutical care pathway for the problems related to chemotherapy， and to evaluate whether it contributes to the detection and intervention of drug-related problems （DRPs） in chemotherapy patients. METHODS The pharmaceutical care pathway table and flow charts were constructed and implemented by pharmaceutical care practice experience. The patients who were admitted to our hospital for chemotherapy before and after the implementation of the pharmaceutical care pathway were divided into control group （before the implementation，60 cases） and observation group （after the implementation，64 cases）， respectively； the relevant medical records of patients in the control group were extracted to evaluate DRPs， and pharmaceutical care of chemotherapy-related problems was performed for patients in observation group to extract DRPs. The basic condition， chemotherapy condition， DRPs classification and intervention status， adverse reactions induced by chemotherapy， PCNE classification of DRPs， occurrence time of DRPs， and drug classes related to DRPs were compared between 2 groups. RESULTS There was no statistical significance in the basic situation， chemotherapy regimen and chemotherapy drug category between the two groups （P＞0.05）. DRPs occurred in 46 and 37 patients in control group and observation group， respectively. In both groups， DRPs mainly occurred during chemotherapy， and mainly in the early stage of chemotherapy. Using the new pathway， the detection of DRPs significantly increased from 52.17% in the control group to 91.89% in the observation group （P＜0.05）. The successful intervention rate of DRPs was significantly increased from 32.61% in the control group to 72.97% in the observation group （P＜ 0.05）. The incidence of adverse drug reactions significantly decreased from 28.33% in the control group to 12.50% in the observation group（P＜0.05）. The main problem type of DRPs in the control group was treatment effectiveness， which mainly involved adjuvant antitumor drugs， mainly due to the use of adjuvant anti-tumor drugs for off-label prescribing； that of the observation group was treatment effectiveness and treatment safety， which mainly involved vomiting drugs， mainly due to insufficient medication to prevent nausea and vomiting caused by chemotherapy. CONCLUSIONS The implementation of the pathway helps clinical pharmacists to detect and intervene in DRPs among chemotherapy patients， and reduces the occurrence of chemotherapy-induced adverse reactions.

Effective Ingredients of Chinese Medicine in Prevention and Treatment of Osteoarthritis by Regulating Oxidative Stress： A Review / 中国实验方剂学杂志

Osteoarthritis （OA） is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs （NSAIDs）， which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA， with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope， multiple targets， and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species （ROS）， relieve oxidative stress （OS） damage， and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde （MDA） and superoxide dismutase （SOD）. Through the modulation of signaling pathways such as nuclear factor E2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa B （NF-κB）， c-Jun N-terminal kinase （JNK）， NOD-like receptor protein 3 （NLRP3）， and osteoprotegerin （OPG）， they downregulated the expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， thereby effectively relieving local joint inflammation， protecting chondrocytes and bone tissue， inhibiting chondrocyte apoptosis， and further alleviating the progression of OA. Currently， there are still certain limitations in the medical research status and development trends of OA， necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA， providing new directions and ideas for future research.

LipoxinA4 protects sepsis-induced acute kidney injury via the TLR4/MyD88/NF-κB pathway / 安徽医科大学学报

Objective To study the protective effect of lipoxin A4(LXA4)against sepsis-induced acute kidney in-jury(SAKI)in rats and its effect on the expression of toll-like receptor 4(TLR4),myeloid differentiation factor88(MyD88),nuclear factor kappa B(NF-κB)in the kidney.Methods Forty male specific pathogen-free C57BL/6J mice were randomly divided into SAKI group,SAKI+LXA4 group,sham procedure group,sham procedure+LXA4 group.The mice in SAKI group and SAKI+LXA4 group were given cecum ligation and puncture(CLP)to establish SAKI animal models.The mice in SAKI+LXA4 group and sham procedure+LXA4 group were given LXA4(40 ng/kg)with intraperitoneal injection 30 mins after CLP.All mice were sacrificed at the 24th hour after CLP to collect serum,urine and kidney tissues.The enzyme linked immunosorbent assay(ELISA)was used to test the serum creat-inine(Scr),blood urea nitrogen(Bun),interleukin-1 β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α)and urine neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule 1(KIM-1)levels of mice.The pathologi-cal changes were examined through hematoxylin-eosin(HE)staining and Periodic Acid-Schiff(PAS)staining.And the mRNA levels of TLR4,MyD88,NF-κB p65 were detected through real-time PCR(RT-PCR);the expression lev-els of TLR4,MyD88,NF-κB p65,phospho-NF-KB p65(p-NF-KB p65)were detected through immunohistochemistry(IHC)and Western blot assay.Results ELISA showed that the values of Scr,Bun,IL-1 β,IL-6,TNF-α,NGAL,KIM-1 in SAKI group were higher than those in SAKI+LXA4 group(P＜0.05),and there were no significant differences in Scr,Bun,IL-1 β,IL-6,TNF-α,NGAL,KIM-1 between sham procedure group and sham procedure+LXA4 group.HE and PAS staining showed that SAKI group had severer pathological changes than SAKI+LXA4 group in the kidney structure(P＜0.05),while pathological structures of the kidney were normal in sham proce-dure group and sham procedure+LXA4 group.RT-PCR showed that the mRNA levels of TLR4,MyD88,N F-κB p65 in SAKI group,SAKI+LXA4 group were higher than sham procedure group and sham procedure+LXA4 group(P＜0.05);the mRNA levels of TLR4,MyD88,NF-κB p65 in SAKI group were higher than SAKI+LXA4 group(P＜0.05);The results of IHC,Western blot assay were as follows:The expression levels of TLR4,MyD88,NF-κB p65,p-NF-κB p65 in SAKI group,SAKI+LXA4 group were higher than sham procedure group and sham procedure+LXA4 group(P＜0.05);the expression levels of TLR4,MyD88,NF-κB p65,p-NF-κB p65 in SAKI group were higher than SAKI+LXA4 group(P＜0.05).Conclusion TLR4/MyD88/NF-KB pathway plays an important role in the occurrence and development of SAKI,and LXA4 may reduce SAKI by inhibiting TLR4/MyD88/NF-κB sig-naling pathway.

Study on application of modified anterior pelvic floor functional reconstruction operation in pelvic organ prolapse / 重庆医学

Objective To analyze the application value of modified anterior pelvic floor reconstruction operation in pelvic organ prolapse.Methods A retrospective analysis was adopted.A total of 141 patients with pelvic floor reconstruction surgery in the obstetrics and gynecology department of Chongqing Municipal Ma-ternal and Child Health Care Hospital from January 2020 to December 2021 were included.The patients were divided into the observation group(modified anterior pelvic floor reconstruction operation,n=78)and control group(classic anterior pelvic floor reconstruction operation,n=63)according to the operation methods.The perioperative indicators,pelvic organ prolapse quantitation(POP-Q)score before and after operation,objective cure rate after operation,recurrence situation and pelvic floor quality of life score before and after operation were compared between the two groups.Results There was no significant difference in the surgical time,bleeding volume,duration of antibacteriakl drug use,and length of hospital stay between the two groups(P＞0.05).The POP-Q scores after surgerynin the two groups were signbificantly increase compared with before operation,and the objective cure rate in postoperative 12 months in the observation group was significantly higher than that in the control group at 12 months after surgery(91％.0 vs.81.0％,P＜0.05).There was no recurrence in the observation group after one year follow-up,while there were two cases of recurrence in the control group.The scores of the pelvic floor distress inventory short form 20(PFDI-20),pelvic floor impact questionnake,short form 7(PFIQ-7),and pelvic organ prolapse/incontinence sexual function questionnaire-12(PISQ-12)in 1 month after surgery in the two groups had statisticallyu significant differences compared with those before surgery(P＜0.05).After one year of follow-up,the patient global impression of improvement(PGI-I)score in the observation group was significantly lower than that in the control group(P＜0.05).Con-clusion The modified anterior pelvic floor reconstruction operation can effectively improve the quality of life in the patients,moreover the patients are not easy to relapse,so which is a new type of operation worthy of promotion.

Study on the Distribution of Traditional Chinese Medicine Constitution in Pregnant Women with Iron Deficiency Anemia and Its Influencing Factors / 广州中医药大学学报

Objective To investigate the distribution of traditional Chinese medicine(TCM)constitution in pregnant women with iron deficiency anemia(IDA)and its related influencing factors,so as to provide a reference for the TCM prevention and treatment of IDA in pregnancy.Methods A total of 109 eligible patients with IDA during pregnancy were included in the study.The general data of pregnant women,the TCM constitution types and relevant laboratory indicators including serum ferritin(Fer),hemoglobin(Hb)and mean corpuscular volume(MCV)were collected.Statistical analyses were conducted on the distribution of TCM constitution types of IDA pregnant women and its related influencing factors as well as the pregnancy outcomes.Results(1)The 109 IDA pregnant women were predominated by biased constitution types,accounted for 60 cases(55.05％).The distribution of the constitution types of 109 IDA pregnant women was as follows:balanced constitution(49 cases,44.95％)>damp-heat constitution(13 cases,11.93％)>yang deficiency constitution(12 cases,11.01％)>yin deficiency constitution(11 cases,10.09％)>qi deficiency constitution(10 cases,9.17％)>qi stagnation constitution(9 cases,8.26％)>blood stasis constitution(3 cases,2.75％)>phlegm-damp constitution(2 cases,1.83％).(2)Comparison of Hb and MCV levels in IDA pregnant women with various constitution types showed no statistically significant differences(P>0.05),but Fer level in IDA pregnant women with damp-heat constitution was significantly higher than that in IDA pregnant women with balanced constitution(P<0.01),and the probability of occurrence of amniotic opacity in IDA pregnant women with damp-heat constitution was significantly higher than that in IDA pregnant women with balanced constitution and other biased constitution types(P<0.05).Conclusion Damp-heat constitution is the most common TCM constitution type in pregnant women with IDA,followed by yang deficiency constitution,yin deficiency constitution and qi deficiency constitution.The damp-heat constitution may be the susceptible constitution of pregnant women with IDA,and IDA pregnant women with damp-heat constitution have significantly higher Fer level than those with balanced constitution,and also have the higher probability of occurrence of amniotic opacity than those with balanced constitution and other biased constitution types.

Investigation on the Correlation Between Traditional Chinese Medicine Constitution and Pathogenic Factors in Patients with Ankylosing Spondylitis / 广州中医药大学学报

Objective To study the correlation between traditional Chinese medicine(TCM)constitution and pathogenic factors in patients with ankylosing spondylitis(AS).Methods One hundred patients of AS and their family members who had medical consultation in the Fifth Hospital of Xi'an(i.e.,Shaanxi Hospital of Integrated Traditional Chinese and Western Medicine)in August 2019 and September 2020 were selected as the study subjects.The guidelines of Classification and Determination of Traditional Chinese Medicine Constitution issued by the China Association of Chinese Medicine were adopted to determine the traditional Chinese medicine(TCM)constitution types of the study subjects.The sociodemographic information,living habits,clinical symptoms,and TCM constitution types of the AS patients and their family members were collected by means of questionnaires and clinical investigations,and then the pathogenic factors of the patients with AS were investigated.The binomial Logistic regression model was used to analyze the correlation between TCM constitution types and pathogenic factors in patients with AS.Results(1)Among the 100 AS patients,the majority of them had the biased constitutions,and the biased constitutions with the occurrence frequency in descending order were yang deficiency constitution,qi deficiency constitution,and damp-heat constitution,which accounted for 33.00%,14.00%,and 18.00%,respectively.(2)The prevalence rates of AS in the first-,second-,and third-degree relatives of AS patients were 56.25%,40.00%and 25.00%,respectively.For the positive rates of human leukocyte antigen B27(HLA-B27)in AS patients and their family members,HLA-B27 in AS patients was all positive,while the positive rates of HLA-B27 in the first-,second-,and third-degree relatives of AS patients were 44.31%,30.67%and 15.63%,respectively.(3)The results of regression analysis showed that the disease duration of AS patients was significantly correlated with qi deficiency constitution,the grading of sacroiliac arthritis was correlated with qi stagnation constitution,and age was correlated with blood stasis constitution(P＜0.05 or P＜0.01).The results indicated that disease duration and age were the important factors affecting the constitution types of AS patients,and disease duration was closely related to qi deficiency while age was closely related to blood stasis.Conclusion AS is a highly hereditary autoimmune disease,and its onset is associated with HLA-B27.Yang deficiency is the basic constitution type of AS,and damp-heat constitution is the main constitution type in the progression of AS(especially in the active stage of the disease).The prolongation of the disease will exacerbate the illness condition of AS and then the manifestations of qi deficiency will be more obvious.

Effect of neferine on diabetic nephropathy by regulating SDF-1/CXCR4 signal pathway / 上海交通大学学报（医学版）

Objective·To investigate the effect of neferine(Nef)on renal tissues of diabetic nephropathy(DN)rats and its related mechanism.Methods·DN model rats were constructed by feeding high-fat diet combined with intraperitoneal injection of streptozotocin,and the successfully constructed rats were randomly divided into DN group,Nef(low,medium and high)dose groups and Nef high-dose+pathway antagonist(AMD3100)group,with 10 rats in each group.At the same time,10 common rats were selected as the normal group.The levels of fasting blood glucose(FBG),24 h urinary protein,serum glycosylated hemoglobin(HbA1c),serum creatinine(Scr),blood urea nitrogen(BUN)and renal index of rats in the six groups were measured.Hematoxylin-eosin(H-E)and Masson staining were used to observe the pathological changes of renal tissues.The content of malondialdehyde(MDA)in renal tissues was determined by thiobarbituric acid(TBA)method,and the activities of superoxide dismutase(SOD)and catalase(CAT)in renal tissues were determined by water soluble tetrazolium(WST-1)method and ammonium molybdate method,respectively.The mRNA and protein expressions of stromal cell-derived factor-1(SDF-1)and CXC chemokine receptor 4(CXCR4)in renal tissues were detected by quantitative real-time PCR(qPCR)and Western blotting,respectively.Rat renal tubular epithelium cells NRK-52E were induced by high glucose(30 mmol/L glucose)to establish DN cell model.The cells were divided into control group,high glucose(HG)group,HG+Nef(low,medium and high)dose(i.e.HG+Nef-L,M and H)group,and HG+Nef-H +AMD3100 group.SOD and CAT activities were detected by WST-1 method and ammonium molybdate method,respectively.MDA content was detected by TBA method.The mRNA and protein expressions of SDF-1 and CXCR4 were detected by qPCR and Western blotting,respectively.CCK-8 method and flow cytometry were used to detect cell viability and apoptosis rate,respecti-vely.Results·Compared with the DN group,the levels of FBG,24 h urinary protein,HbA1c,Scr,BUN,renal index and MDA content in Nef(low,medium and high)dose groups and Nef high-dose+AMD3100 group were decreased,the mRNA and protein expressions of SDF-1 and CXCR4 were increased,and the activities of SOD and CAT were increased(all P<0.05).The degree of pathological damage and fibrosis of renal tissues was reduced;all of the above changes were dose-dependent.AMD3100 could weaken the renal protective effect of high-dose Nef on DN rats.Compared with the HG group,NRK-52E cell viability,SOD and CAT activities,and the mRNA and protein expressions of SDF-1 and CXCR4 were increased in HG+Nef-L,M and H groups,while apoptosis rate and MDA content were decreased(all P<0.05).AMD3100 could reverse the protective effect of Nef-H on NRK-52E cell damage.Conclusion·Nef may control blood glucose levels on DN rats and improve antioxidant capacity by activating the SDF-1/CXCR4 signal pathway,playing a renal protective role.

Severity of loneliness and factors associated with social and emotional loneliness among the elderly in three districts in Shanghai / 复旦学报（医学版）

Objective To explore the severity of loneliness among the elderly in communities in Shanghai,and to identify factors associated with social and emotional loneliness respectively.Methods A cross-sectional study was conducted in older adults aged 65 years or above in Pudong New Area,Jing'an District and Huangpu District in Shanghai from Mar to Jun 2021.In Pudong New Area,multi-stage stratified random sampling was conducted based on the age and gender distribution of Shanghai,while in Huangpu District and Jing'an District convenience sampling was conducted.A total of 635 samples were included in the study.Loneliness was assessed using the De Jong Gierveld Loneliness Scale with social and emotional loneliness subscales.Logistic regression analyses were conducted to identify factors associated with social and emotional loneliness.Results Among the 635 participants,only 53 older adults(8.4%)were not lonely.Female(OR=0.46,95%CI:0.31-0.70),higher self-efficacy(OR=0.97,95%CI:0.94-1.00),more objective social support(OR=0.96,95%CI:0.93-0.99)were associated with less severe social loneliness.Meanwhile,higher level of education(secondary education,OR=0.56,95%CI:0.34-0.95;college or above,OR=0.30,95%CI:0.11-0.83)and higher self-efficacy(OR=0.96,95%CI:0.93-0.99)were associated with less severe emotional loneliness,while depression(OR=3.41,95%CI:1.76-6.60)and worse social capital(OR=2.02,95%CI:1.29-3.16)were associated with more severe emotional loneliness.Conclusion Up to 91.6%of the elderly in our study sample were moderately lonely or above.The factors associated with social loneliness include self-efficacy,gender and social support.The factors associated with emotional loneliness are self-efficacy,education level,depression,and social capital.