OBJECTIVE To investigate the ameliorating effect and mechanism of the effective substance groups from Artemisia ordosica（Abbreviated as HSH） on rheumatoid arthritis （RA） based on cluster of differentiation 4/lymphocyte cell-specific protein- tyrosine kinase/zeta-chain-associated protein kinase of 70 kDa/interleukin-17（CD4/LCK/ZAP70/IL-17） signaling pathway. METHODS The rats were divided into normal group， model group， HSH low-dose， medium-dose and high-dose groups （2.7， 10.8， 21.6 mg/kg） and positive control group （Tripterygium glycosides tablet， 6.3 mg/kg）， with 10 rats in each group. Except for normal group， RA rat model was induced by complete Freund’s adjuvant in other groups. After modeling， each group was given relevant medicine or normal saline intragastrically， once a day， for 28 consecutive days. The changes in ankle joint swelling and arthritis index in rats were determined； the pathological changes of ankle joint tissue were observed； the levels of inflammatory factors [IL-1β， IL-21， IL-17A， IL-2， interferon-γ （IFN-γ） and IL-6] in serum and joint fluid of rats were determined； the levels of Th1， Th17 and Treg cells in the whole blood and spleen of rats were detected； protein and mRNA expressions of LCK， proto-oncogene tyrosine-protein kinase Fyn （Fyn）， ZAP70， CD45， RAR-related orphan receptor γt （RORγt）， and forkhead box protein 3 （Foxp3） in ankle synovial tissue were determined. RESULTS Compared with normal group， the changes in ankle joint swelling， arthritis index， the levels of IL-1β， IL-21， IL-17A， IL-2， IFN-γ and IL-6 in serum and joint fluid， the levels of Th1， Th17 cells and Th17/Treg value in whole blood and spleen， and the protein and mRNA expression levels of LCK， Fyn， ZAP70， CD45， and RORγt in ankle joint synovium were all significantly increased/elevated （P＜0.05）. The level of Treg cells in the spleen， as well as the protein and mRNA expression levels of Foxp3 in the ankle joint synovium were significantly decreased （P＜0.05）. Compared with model group， most of the above-mentioned indicators were significantly reversed in the positive control group and all dose groups of HSH （P＜0.05）. The degree of pathological changes in ankle joint tissues was markedly improved， and inflammation was alleviated. CONCLUSIONS HSH can regulate the cascade reactions in the CD4/LCK/ZAP70/IL-17 pathway within the T-cell receptor signaling pathway， thereby modulating the Th17/Treg balance. This leads to the suppression of inflammatory responses and the alleviation of synovial tissue damage in rats with RA.

OBJECTIVE To explore the effect of Jinkui shenqi pill and its potential mechanism on diabetic nephropathy-related osteoporosis （DNOP） in rats. METHODS The rats were randomly divided into blank control group， control group， model group， Jingui shenqi pill low-， medium- and high-dose groups （0.62， 1.24， 2.48 g/kg）， and positive control group （denosumab 3 mg/ kg）， with 12 cases in each group. Except for the blank control group and the control group， models of DNOP were constructed in the remaining groups by high-glucose and high-fat forage， 3% fructose solution for feeding+intraperitoneal injection of streptozotocin solution. At 2 d after successful molding， Jingui shenqi pill low-， medium- and high-dose groups， and positive control group were given intragastric administration or subcutaneous injection of the corresponding drugs， once a day， for consecutive 8 weeks. After the last administration， bone mineral density （BMD） and serum bone metabolism-related indexes [osteocalcin （OC）， calcium， phosphorus， alkaline phosphatase （ALP）， tartrate-resistant acid phosphatase （TRAP）] were detected. The pathological changes of right femoral tissues were observed， and the expressions of receptor activator of NF-κB ligand （RANKL）/receptor activator of NF-κB （RANK）/osteoprotegerin （OPG） pathway-related mRNAs and proteins in left femoral tissues were detected. RESULTS Compared with the blank control group and the control group， there was rupture of bone trabecula and severe structural damage in the model group， and tissue space was obvious. BMD and ALP activities， mRNA and protein expressions of OPG were significantly decreased or down-regulated， while the levels of OC， calcium and phosphorus， TRAP activity， mRNA and protein expressions of RANKL and RANK were significantly increased or up-regulated （P＜0.05）. Compared with the model group， the number of bone trabeculae was increased in all Jingui shenqi pill groups， and the arrangement of bone trabeculae was more regular and dense. The above indexes generally were improved in a certain dose-dependent manner （P＜0.05）. CONCLUSIONS Jingui shenqi pill can promote osteogenesis and regulate the balance of bone metabolism in DNOP rats， which may be related to down-regulating the expressions of RANKL and RANK， and up-regulating the expression of OPG.

OBJECTIVE From the perspective of China’s health system， to evaluate the economic efficiency of Irinotecan liposome+fluorouracil+calcium folinate+oxaliplatin（NALIRIFOX regimen） versus paclitaxel （albumin-bound） combined with gemcitabine （AG regimen） in the first-line treatment of metastatic pancreatic cancer. METHODS A dynamic Markov model was constructed based on the data from the NAPOLI 3 clinical trial， with a cycle period of 28 days and a simulation time limit of 5 years. Incremental cost-effectiveness ratio （ICER） and quality-adjusted life year （QALY） were used as the model output indicators. The willingness-to-pay （WTP） threshold was set at three times China’s 2024 per capita gross domestic product （GDP）， and a discount rate of 5% was adopted. A cost-utility analysis was conducted to analyze the economic efficiency of the NALIRIFOX regimen compared to the AG regimen. Univariate sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the robustness of the model results， and scenario analysis was conducted by reducing the cost of irinotecan liposome by 60% and 70%. RESULTS The base-case analysis showed that the ICER of the NALIRIFOX regimen was 854 669.96 yuan/QALY compared to the AG regimen， which was greater than the WTP threshold （287 247 yuan/QALY）， indicating that the NALIRIFOX regimen was not economically efficient. The univariate sensitivity analysis results indicated that the discount rate， the cost of irinotecan liposome， the utility value of the progression-free survival state， and the utility value of the disease progression state had a significant impact on the ICER. The probabilistic sensitivity analysis results showed that under the WTP threshold of this study， the NALIRIFOX regimen was not economically efficient compared with the AG regimen. The scenario analysis results indicated that when the price was reduced by 70%， the probability of the NALIRIFOX regimen being economically efficient compared with the AG regimen was 9.60%. CONCLUSIONS From the perspective of China’s health system， when the WTP threshold is set at three times China’s 2024 per capita GDP， the NALIRIFOX regimen is not economically efficient in the first-line treatment of metastatic pancreatic cancer， compared with the AG regimen.

Acute hematogenous pulmonary tuberculosis (AHPTB) during pregnancy, combined with acute respiratory distress syndrome (ARDS) and septic shock, is a rare and fatal condition. The two reported patients both underwent in vitro fertilization and embryo transfer (IVF-ET) to assist in pregnancy due to tubal factors. They developed critical AHPTB after pregnancy and subsequently developed respiratory failure. After assisted breathing, early anti tuberculosis treatment, and symptomatic treatment, both patients improved their condition. For women who are pregnant after IVF-ET due to tubal infertility in areas with high incidence of tuberculosis, if they have persistent fever, cough, expectoration and vaginal bleeding during pregnancy, they should be alert to the possibility of tuberculosis and be screened as soon as possible. For patients with pregnancy complicated with AHPTB, active treatment and vigilance against worsening of the condition should be taken.

Objective To investigate the effect of cholecystokinin octapeptide(CCK-8)on glutamate transporter 1(GLT-1)expression in hippocampal astrocytes induced by glutamate(Glu).Methods The mouse hippocampal astrocytes were isolated and the toxicity of CCK-8 at different concentrations on the mouse hippocampal astrocytes was detected.The cells were divided into control group,Glu group,Glu+0.1 μmol/L CCK-8 group,Glu+0.5 μmol/L CCK-8 group and Glu+1.0 μmol/L CCK-8 group.MTT assay was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis.Biochemical kit was used to detect Glu content in the extracellular supernatant,and qRT-PCR was used to detect the mRNA expression of GLT-1 and glutamate/aspartate transporter(GLAST).The protein expressions of Caspase-3,Bcl-2,GLT-1 and GLAST were detected by Western blotting,and the expression of TNF-α in the cell supernatant was detected by ELISA.Results CCK-8 at different concentrations had no significant effect on the proliferation of mouse hippocampal astrocytes.Compared with the control group,the cell proliferation ability and the expression levels of Bcl-2 protein,GLT-1 and GLAST mRNA and protein in Glu group were significantly decreased(all P＜0.01),the apoptosis rate,extracellular Glu content,Caspase-3 protein expression level in cells and TNF-α level in cell supernatant were significantly increased(all P＜0.01);Compared with the Glu group,the cell proliferation a-bility and the expression levels of Bcl-2 protein,GLT-1 and GLAST mRNA and protein in the Glu+0.5 μmol/L CCK-8 group and Glu+1.0 μmol/L CCK-8 group were significantly increased(all P＜0.05),the apoptosis rate,extracellular Glu content,Caspase-3 protein expression level in cells and TNF-α level in cell supernatant were significantly decreased(all P＜0.01).Con-clusion CCK-8 can inhibit Glu-induced inflammatory response of astrocytes,promote the expression of GLT-1,reduce the con-centration of extracellular Glu,promote cell proliferation and inhibit apoptosis.

There are millions of patients with taxane-induced peripheral neuropathy （TIPN）， and there is no effective treatment or prevention measure in clinical practice. The occurrence of TIPN may be related to the dosage form of paclitaxel drugs， genetic and molecular markers， drug dosage and chemotherapy cycle， patient factors， etc. At present， drugs for treating TIPN mainly include those that inhibit axonal degeneration （such as dosazosin， tamsulosin）， prevent mitochondrial dysfunction （such as glutathione trisulfides， antioxidants α -lipoic acid）， improve calcium imbalance in the internal environment （Shaoyao gancao decoction， N-type voltage-gated calcium channel inhibitor IPPQ）， and inhibit neuroinflammation （such as chemokine inhibitors and selective interleukin-8 receptor inhibitors DF2726A）. Further exploration of drug treatment strategies targeting different induction mechanisms is expected to become a new direction for precise clinical prevention and personalized treatment of TIPN.

Inflammation is a key player in various pathophysiological processes and diseases, especially throughout the gestational cycle, and inflammation plays an important role in ovulation, embryo implantation, placental formation, and all stages of pregnancy maintenance. However, excessive inflammatory activity can impair endometrial receptivity, which can lead to clinical problems such as infertility, recurrent implantation failure, and recurrent miscarriage, which in turn can negatively impact women's reproductive health and pregnancy outcomes. Studies have shown that about two-thirds of embryo implantation failures are associated with inadequate endometrial receptivity. Therefore, the precise regulation of inflammatory states is of great significance for increasing pregnancy rates and improving pregnancy outcomes.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine and metabolic disease, and its pathogenesis is closely related to inflammation, insulin resistance, and metabolic disorders. Bilirubin is the final product of the destruction and degradation of senescent red blood cells in the body. In addition, bilirubin can be not only used to evaluate liver function damage and cytotoxicity, but also can anti-inflammatory, antioxidant, alleviate metabolic disorders, etc. Recently, studies have found a certain correlation between low levels of bilirubin and PCOS: the level of bilirubin in patients with PCOS is low, and the anti-inflammatory and antioxidant properties of bilirubin may play a protective role in the pathogenesis of PCOS.

Inflammation is the basic pathological process of a variety of diseases, which involved in the occurrence and development of female infertility-related diseases, especially in bacteria and viruses infection of reproductive system, resulting in infertility. However, inflammatory reactions and factors also exist in normal physiological processes, such as endometrial morphologic changes in menstrual cycles, follicle genesis, ovulation, luteinization, pregnancy, etc. In addition, inflammation is also involved in the occurrence of some reproductive endocrine and metabolic diseases, such as obesity, endometriosis, polycystic ovary syndrome and so on. In the past, the understanding to inflammation in reproductive system was mostly limited to the inflammatory diseases and resulted in fertility decline or sterility, infertility, and other problems, which was not comprehensive. This review summarized the normal physiological inflammation and disease-related inflammation in the reproductive system, and described the evaluation of inflammatory state, as well as relevant prevention and treatment suggestions.

Objective:To compare the efficacy and safety of standard treatment with or without adjuvant chemotherapy in patients with highly malignant non-metastatic prostate cancer.Methods:In this prospective non-randomized controlled study, consecutive non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or Gleason score of 5 admitted to Peking University First Hospital were enrolled. Four to six cycles of chemotherapy using docetaxel ± carboplatin regimen were added or not after standard radical therapy. The primary end point was 5-year event-free survival (EFS), and the secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. The survival curve was drawn by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test.Results:A total of 176 patients were consecutively enrolled from November 2019 to January 2022 of which 138 patients received only standard radical therapy (control group), and 38 patients received adjuvant chemotherapy after standard radical therapy (chemotherapy group). The median follow-up time was 13.4 (2.0-34.0) months. All patients survived. The 30-month EFS rates in the chemotherapy and control groups were 100% and 85.6%, respectively ( P=0.064). There were no events in the chemotherapy group, while there were 12 cases of events in the control group, including 6 cases of biochemical recurrence and 6 cases of imaging progression. The 30-month MFS rates in two groups were 100% and 91.9%, respectively ( P=0.205). After the 1 vs. 2 propensity score matching, the EFS and MFS rates in two groups were 100% vs. 85.7% ( P=0.056), and 100% vs. 92.2% ( P=0.209), respectively. The incidence rates of grade 2 and above urinary toxicity in the chemotherapy and control groups were 2.6% and 7.2% ( P=0.354), respectively. The incidence rates of grade 2 and above rectal toxicity were 5.3% and 5.1% ( P=0.711), respectively. Grade 3 and above chemotherapy-related toxicity in the chemotherapy group were leukopenia (31.6%), thrombocytopenia (2.6%) and alopecia (13.2%). Conclusion:The addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall EFS of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.