OBJECTIVE To explore the effects of 5，10-methylenetetetrahydrofolate reductase （MTHFR） gene polymorphism on the adverse reactions in patients with osteosarcoma after the first high-dose methotrexate （HD-MTX） treatment. METHODS A prospective study was conducted to include 53 patients with osteosarcoma treated with HD-MTX at the first admission in General Hospital of Eastern Theater Command. The dose of MTX was evaluated according to the polymorphism of rs1801133 in the METHFR gene and demographic factors， then whole pharmaceutical monitoring was conducted. The data on liver toxicity， renal toxicity， hematological toxicity， and gastrointestinal reaction were collected after the first chemotherapy cycle. Single factor analysis and binary Logistic regression analysis were used to analyze the correlation between MTX dose， 24 h blood drug concentration， and rs1801133 locus genotype with four adverse reactions. RESULTS The MTX dosage in patients with CC wild type was significantly higher than that in TT mutant type （7.97 g/m2 vs. 6.98 g/m2， P＝0.030）， but this difference did not affect the 0 h and 24 h blood drug concentrations of MTX. The above four adverse reactions were not related to the dose of MTX. The results of binary Logistic regression analysis showed that carrying one T allele increased the risk of developing hematological toxicity by 4.13 times（95% confidence interval：1.35-12.62，P＝0.013）. When 24 h plasma concentration threshold of MTX was set to 2.65 µmol/L， the sensitivity and specificity of predicting liver function damage were 53.33% and 86.96%， respectively； when the threshold was set to 7.28 μmol/L， the sensitivity and specificity of predicting renal damage were 100% and 81.63%. CONCLUSIONS The polymorphism of the rs1801133 in the MTHFR gene is associated with hematological toxicity of MTX. Patients who take HD-MTX for the first time and carry the T allele have a high risk of hematological toxicity. The 24 h plasma concentration of MTX is related to liver toxicity and renal toxicity. In addition， monitoring the 24 h blood drug concentration can predict liver and renal toxicity， and take early intervention.

Objective:To investigate the relationship between adiponectin (ADIPOQ) gene polymorphism and postpartum type 2 diabetes mellitus (T2DM) in pregnant women with gestational diabetes mellitus (GDM).Methods:A retrospective study was conducted on 236 GDM postpartum women admitted to the Affiliated Hospital of Jining Medical College from June 2020 to June 2021 as observation subjects. They were divided into a T2DM group and a non T2DM group based on the occurrence of T2DM after delivery. The clinical data of the two groups were compared. The double deoxygenation end termination method was used to detect the single nucleotide polymorphism (SNP) of the ADIPOQ gene, and the four loci rs17366568, rs822395, rs1501299, and rs2241766 were classified. The relationship between ADIPOQ genotype polymorphism and postpartum T2DM was analyzed using a logistic regression model.Results:The G allele carrying the rs2241766 locus in ADIPOQ gene was negatively correlated with the occurrence of T2DM ( OR=0.71, 0.68, P<0.05). Compared with T2DM patients with TT genotype, the GT+ GG genotype at the rs2241766 locus had a lower risk of occurrence for gestational age ≥2 and HbA 1c>85%. Similarly, T2DM patients with pre pregnancy body mass index (BMI)>25 kg/m 2 were more likely to be carriers of the rs2241766 TT genotype ( P=0.026). The (GT+ TT) genotype carrying the T allele at the rs1501299 locus was a protective factor for gestational age and HbA 1c in T2DM patients. Conclusions:The rs2241766 and rs1501299 polymorphisms of the ADIPOQ gene are associated with susceptibility to postpartum T2DM in GDM women. Individuals with rs2241766 and rs1501299 mutant genotypes belong to the high-risk population for T2DM.

Methicillin-anti staphylococcus aureus(MRSA) is one of the common pathogenic bacteria in hospital infection. Many asymptomatic MRSA carriers have been found in clinical practice, which can not only transmit the strain to others, but also cause secondary infection due to their own reasons. Decolonization measures can reduce the number of MRSA colonizers, thereby reducing the risk of endogenous infection and secondary transmission. Early identification is the first step to prevent transmission and secondary infection, which requires high accuracy and sensitivity of detection methods. Xpert MRSA/SA assay (Cepheid, Sunnyvale, CA, USA) may be a better choice, which can shorten the time of traditional methods, and has high specificity and sensitivity. Unlike other rapid detection methods, the Xpert MRSA/SA assay may be more suitable for MRSA colonisation detection.

ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg^-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg^-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg^-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.

OBJECTIVE To investigate the effect mechanism of Gualou guizhi granule on neurological function and synaptic plasticity in rats with cerebral ischemia-reperfusion injury. METHODS The rats were randomly divided into sham operation group， model group and Gualou guizhi granule group （3.6 g/kg）， with 6 rats in each group. The cerebral ischemia-reperfusion injury model was established by the suture occlusion method. Two hours after modeling， the model rats were given relevant medicine or normal saline intragastrically， once a day， for 7 consecutive days. After the last medication， the neurological function of rats was evaluated [calculated by modified neurological severity scores （mNSS） and corner turning percentage]； the neuronal apoptosis rate of brain histiocyte in the ischemic side of rats was detected in each group； the positive expressions of growth associated protein 43 （GAP43） and microtubule associated protein 2 （MAP2） were detected； protein expressions of neuron-specific nuclear protein （NeuN）， synaptophysin-1 （Syn-1）， postsynaptic density protein-95 （PSD-95）， peroxisome proliferators-activated receptor γ （PPARγ）， brain-derived neurotrophic factor （BDNF） and tropomyosin receptor kinase B （TrkB）， as well as mRNA expressions of NeuN， Syn-1 and PSD-95 were detected. RESULTS Compared with the model group， mNSS， corner turning percentage and neuronal apoptotic rate were decreased significantly in Gualou guizhi granule group （P＜0.01）； GAP43 represented weak immunoreactivity， and MAP2 represented moderate immunoreactivity； protein expressions of NeuN， Syn-1， PSD-95， PPARγ， BDNF， TrkB and mRNA expressions of Syn-1， NeuN， PSD-95 were all increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Gualou guizhi granule can promote synaptic plasticity by activating BDNF/TrkB signaling pathway， thus playing a protective role in cerebral ischemia-reperfusion injury in rats.

Ruxolitinib， a small molecule inhibitor， selectively targets Janus kinase （JAK） by competitively binding to adenosine triphosphate on the catalytic site of the JAK1 and JAK2 domain， thereby inhibiting JAK activation and signal transducer and activator of transcription （STAT） phosphorylation and prevents the expressions of the JAK-STAT signaling pathway. Oral ruxolitinib has demonstrated promising efficacy for myelofibrosis and polycythemia vera. The topical Ruxolitinib cream， approved by the US FDA as the first non-segmental vitiligo home treatment drug， is set to be launched in domestic medical pioneer areas in August 2023 and is expected to bring about a breakthrough in the treatment of vitiligo. Clinical cases have also shown that Ruxolitinib cream has significant curative effects on atopic dermatitis， alopecia areata， and other conditions， indicating great application prospects.

In recent years, the incidence of obesity has been rapidly increasing, greatly elevating the incidence of hypertension, heart disease, non-alcoholic fatty liver disease, and other diseases. Reducing the incidence of obesity has become the focus of global concern. There is an urgent need to find effective and safe treatment method. More and more evidence support the efficacy of auricular acupoint therapy for obesity. It has the advantages of safety, effectiveness, convenience, and cheap. This article intends to discuss the research status of auricular acupoint therapy for obesity based on theoretical development, mechanism exploration, and technical innovation in order to promote the clinical application of auricular acupoint therapy for obesity. At present, with the help of multiple disciplines, inheriting and enriching the theoretical connotation of auricular point therapy for obesity, confirming its clinical effectiveness and safety, clarifying its effect mechanism in the treatment of obesity, and improving the traditional auricular acupoint therapy are feasible directions to promote auricular point therapy in the treatment of obesity, and it can make auricular point therapy have a broader application prospect.

Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a pivotal role in regulating glycolipid metabolism;nevertheless,its obesity-combatting potency remains unclear.In this study,a substantial reduction was observed in serum PPP1R3G levels in high-body mass index(BMI)and high-fat diet(HFD)-exposed mice,establishing a positive correlation between PPP1R3G and non-12α-hydroxylated(non-12-OH)BA content.Additionally,hepatocyte-specific overexpression of Ppp1r3g(PPP1R3G HOE)mitigated HFD-induced obesity as evidenced by reduced weight,fat mass,and an improved serum lipid profile;hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology.PPP1R3G HOE considerably impacted systemic BA homeostasis,which notably increased the non-12-OH BAs ratio,particularly lithocholic acid(LCA).16S ribosomal DNA(16S rDNA)sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population,and elevating the relative abundance of Blautia,which exhibited a positive correlation with serum LCA levels.A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiota-dependent.Mechanistically,PPP1R3G HOE markedly suppressed hepatic cholesterol 7α-hydroxylase(CYP7A1)and sterol-12α-hydroxylase(CYP8B1),and concurrently upregulated oxysterol 7-α hydroxylase and Takeda G protein-coupled BA receptor 5(TGR5)expression under HFD conditions.Furthermore,LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels.These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis,which may serve as potential ther-apeutic targets for obesity-related disorders.

Objective:To explore the efficacy and safety of low-and medium-intensity resistance exercise in patients with chronic heart failure(CHF)combined with sarcopenia.Methods:In the randomized controlled study, 100 elderly patients with CHF combined with sarcopenia who were hospitalized in the Department of Cardiology of the Second Affiliated Hospital of Baotou Medical College from October 2020 to August 2022 were selected and divided into the control group and the intervention group according to the randomized numerical scale method.In the control group, angiotensin-converting enzyme inhibitors/angiotensin receptor inhibitors, β receptor antagonists, diuretics and other standard heart failure medications were routinely given, as well as nutritional support, health education and guidance; in the intervention group, low-intensity resistance exercise was given in addition to the treatment of the control group, and the two groups were evaluated for the NYHA cardiac function classification, grip strength, 5 times sitting time, 6-meter walking time, serum B-type natriuretic peptide level before and after 12 weeks of treatment; limb skeletal muscle mass index(ASMI), visceral fat area, extracellular water ratio were measured by body composition analyzer; right ventricular internal diameter, left atrial internal diameter, left ventricular end-diastolic internal diameter, left ventricular ejection fraction(LVEF) were measured by echocardiography.Changes in each index before and after treatment were compared between the 2 groups.Serious adverse cardiovascular events related to training were followed up by outpatient clinic visits or telephone at 4-week interval over 12 weeks.Results:30 cases were dislodged because they could not adhere to the exercise or could not follow up on time, and finally 70 patients were included, 27 in the control group and 43 in the intervention group.Compared with pre-treatment, grip strength[(17.73±4.54)kg vs.(17.00±4.32)kg, t=8.969], limb skeletal muscle mass[(17.57±3.41)kg vs.(17.24±3.34)kg, t=7.170], and ASMI[(6.02±0.72)kg/m 2vs.(5.85±0.67)kg/m 2, t=6.866]were elevated in the intervention group after 12 weeks(all P<0.05); 5 times sitting up time[(16.17±3.25)s vs.(14.54±3.21)s, t=12.808, ]and 6-meter walking time[(12.30±3.24)s vs.(10.76±3.14)s, t=9.391]shortened(all P<0.05).Compared with pre-treatment, the intervention group showed reduced left ventricular end-diastolic internal diameter[(59.62±9.07)mm vs.(58.48±9.71)mm, t=4.552], increased LVEF[(34.69±7.93)% vs.(35.88±7.92)%, t=4.752], and increased extracellular water ratio[(39.27±7.74)% vs.(38.92±7.41)%, t=6.058]after 12 weeks(all P<0.05).At 12 weeks of follow-up, no training-related serious adverse events occurred in the intervention group.The difference in the incidence of serious adverse cardiovascular events between the two groups(3.70% vs.2.33%, P>0.05)was not statistically significant. Conclusions:Treatment combined with low-and moderate-intensity resistance exercise improves muscle mass, muscle strength, physical function, and cardiac function in elderly patients with CHF combined with sarcopenia without increasing the incidence of adverse events.