ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

ObjectiveTo observe the analgesic efficacy and safety of Qihuang acupuncture theory combined with opioid analgesics in patients with moderate to severe cancer pain due to lung cancer. MethodsPatients with moderate to severe cancer pain from lung cancer were randomly divided into Qihuang acupuncture group and control group， with 33 cases in each group. The control group was treated with long-acting opioid analgesics at maintenance doses and supplementary analgesic medications as needed. In case of breakthrough pain， short-acting opioids were used for rescue. The Qihuang acupuncture group received Qihuang acupuncture treatment in addition to the treatment used in the control group， administered once every other day， with 3 sessions constituting one treatment course. The treatment duration for both groups was 5 days. The primary outcome was the change in pain intensity， measured using the numerical rating scale （NRS） before and after treatment， and the NRS change rate was calculated. Secondary endpoints included the daily NRS change rate， the Eastern Cooperative Oncology Group （ECOG） Performance Status （PS） score， the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire （EORTC QLQ-C30） score， and the 24-hour equivalent hydrocodone sustained-release tablet dose. Laboratory tests， including routine blood， urine， stool， liver function， and kidney function， were performed before and after treatment. Adverse events were recorded throughout the trial. ResultsAll patients completed the trial， and both groups showed a decrease in average NRS scores and PS scores after treatment， with the Qihuang acupuncture group showing lower average NRS scores and PS scores than the control group （P＜0.05 or P＜0.01）. After treatment， the NRS change rate in the Qihuang acupuncture group was （0.42±0.17）， significantly higher than that in the control group （0.14±0.27， P＜0.01）. The daily NRS change rate during treatment was also higher in the Qihuang acupuncture group compared to the control group （P＜0.01）. The Qihuang acupuncture group showed an increase in overall health status and functional scores in the EORTC QLQ-C30， and a decrease in symptom scores for fatigue， nausea and vomiting， pain， dyspnea， insomnia， appetite loss， constipation， and financial difficulties. In contrast， overall health status and constipation scores in the control group increased， while scores of fatigue， nausea and vomiting， pain， and appetite loss decreased （P＜0.05 or P＜0.01）. After treatment， the 24-hour equivalent hydrocodone sustained-release tablet dose did not show significant difference in the Qihuang acupuncture group （P＞0.05）， while the control group showed a significant increase in the 24-hour dose （P＜0.01）. No significant abnormalities were observed in laboratory tests before and after treatment in either group. During the study， the incidence of nausea and vomiting as well as constipation in the Qihuang acupuncture group was both 3.03% （1/33）， while the incidence in the control group was 27.27% （9/33） and 36.36% （12/33）， respectively， with the Qihuang acupuncture group showing significantly lower incidence （P＜0.01）. No serious adverse reactions were observed in either group. ConclusionQihuang acupuncture therapy combined with opioid analgesics is more effective than using opioids alone in relieving pain in patients with moderate to severe cancer pain due to lung cancer. It can improve the patients' physical condition and quality of life， reduce the dose of opioid analgesics， and has good safety.

Objective To investigate the effects of Aconite decoction （AD） on the viability and polarization of murine RAW264.7 macrophages induced by lipopolysaccharide （LPS） or interleukin-4 （IL-4）. Methods Cytotoxicity of AD was assessed by the CCK-8 assay. RAW264.7 cells were polarized toward M1 phenotype by LPS or M2 phenotype by IL-4, followed by treatment with varying concentrations of AD. Macrophage polarization was analyzed by flow cytometry. Quantitative PCR was performed to measure mRNA expression of polarization-associated markers （IL-6, iNOS, Arg1, and Ym1）. ELISA was used to quantify secreted cytokines （TNF-α and IL-10）in the supernatant. Results At non-toxic concentrations, IL-6 and iNOS mRNA levels in LPS-stimulated cells were significantly upregulated while Arg1 and Ym1 expression in IL-4-treated groups were downregulated by AD. Concurrently, TNF-α secretion in LPS-induced M1 polarization was enhanced but IL-10 production in IL-4-induced M2 polarization was suppressed by AD. Conclusion AD could promote macrophage proliferation and viability, augments LPS-driven M1 polarization, and inhibit IL-4-mediated M2 polarization, which provided experimental evidence for the potential application of AD in tumor immunotherapy.

Objective To generate and characterize natural killer cell (NK cell)-conditional Cd226 gene knockout mice using Cre-loxP technology, and to explore the role of CD226 on NK cells in alleviating intestinal inflammation in a murine model of ulcerative colitis (UC). Methods NK cell-conditional Cd226 gene knockout mice were generated by crossing loxP-flanked Cd226 mice with Ncr1-Cre mice via the Cre-loxP system. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used for genotyping. A UC model was established by dextran sulfate sodium (DSS) induction. Flow cytometry was performed to analyze CD226 expression levels on NK cells and the infiltration of related immune cells in colon tissues. Hematoxylin-eosin (HE) staining was performed to assess the degree of colonic inflammation. Results DNA gel electrophoresis and flow cytometry confirmed the successful generation of NK cell-specific Cd226 knockout mice. After conditional knockout of Cd226 in NK cells, inflammation in the UC mouse model was alleviated. Flow cytometry results showed a reduced proportion of NK cells in peripheral blood and the colon lamina propria, while HE staining demonstrated attenuated inflammatory responses. Conclusion Specific knockout of Cd226 in NK cells mitigates intestinal inflammation in UC mice by reducing NK cell numbers and inhibiting their pro-inflammatory functions.
Animals ; Colitis, Ulcerative/pathology* ; Killer Cells, Natural/metabolism* ; Mice, Knockout ; T Lineage-Specific Activation Antigen 1 ; Antigens, Differentiation, T-Lymphocyte/genetics* ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Male

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Thirteen novel diterpenoids, comprising seven tiglianes (walliglianes G-M, 1-7), four rhamnofolanes (wallinofolanes A-D, 8-11), and two daphnanes (wallaphnanes A and B, 12 and 13), together with two known rhamnofolane diterpenoids (euphorwallside H and euphorwallside I, 14 and 15), were isolated and characterized from Euphorbia wallichii(E. wallichii). The chemical structures of these compounds were elucidated through nuclear magnetic resonance (NMR), mass spectrometry (MS), and quantum chemical calculations. Compounds 9 and 11 demonstrated protective effects against H₂O₂-induced BV-2 microglial cell damage. Molecular docking analyses indicated that compound 9 exhibited binding affinity to the anti-oxidant-related targets HMGCR, GSTP1, and SHBG.
Euphorbia/chemistry* ; Antioxidants/isolation & purification* ; Diterpenes/isolation & purification* ; Molecular Structure ; Mice ; Molecular Docking Simulation ; Animals ; Hydrogen Peroxide/toxicity* ; Cell Line ; Microglia/drug effects*

Huangqin Decoction is a classic formula published in the Catalogue of Ancient Classical Famous Prescriptions(the Sec-ond Batch).This paper systematically collates,researches and analyzes the ancient and modern clinical literature that records Huan-gqin Decoction,sorts out key issues such as the prescription origin,composition,medicine origin,processing method,usage and dos-age,efficacy and indications of Huangqin Decoction,and performs predictive analysis on its quality markers(Q-Marker)to provide lit-erature and theoretical support for the clinical application and preparation development of Huangqin Decoction from the entire process of textual research-preparation development-quality evaluation.After analysis and research,it is found that Huangqin Decoction is de-rived from Zhang Zhongjing's Treatise on Cold Damage.It consists of Scutellaria baicalensis,Radix Paeoniae Alba,and Glycyrrhiza,with Jujube serving as the guiding herb.The medicine origin follows the 2020 edition of the Chinese Pharmacopoeia.Scutellaria ba-icalensis and Radix Paeoniae Alba are taken in the raw form;Glycyrrhiza is lightly fried and Jujubes with sliced pieces.The doasge of medicine is 11.19 of Scutellaria baicalensis,7.46 g of Radix Paeoniae Alba and Glycyrrhiza,and jujubes are added or subtracted ac-cording to the situation.The method of preparation and administration is that all herbs are added with 2 000 mL of water,decocting to 600 mL.The decoction can be consumed warm 3 times a day at any suitable time.The formula was commonly used in ancient times for dysentery,but now it is also used for other digestive system diseases such as ulcerative colitis and chronic colitis,which are mainly characterized by diarrhea.The suggested Q-markers for Huangqin Decoction are baicalin,baicalein,wogonin,paeoniflorin,glycyrrhi-zin and glycyrrhizic acid.

Objective To formulate a pharmaceutical service pathway to standardize the pharmacists'whole process of pharmaceutical services for breast cancer patients in medical institutions,promote the standardization of pharmacists'work and improve the rationality of drug use for breast cancer patients in medical institutions.Methods The editorial committee aimed at several challenging problems in the whole process of pharmaceutical services for breast cancer patients in medical institutions through systematic search,referring to the latest domestic and international guidelines and expert consensus of breast cancer and under the relevant drug administration regulations in China,collected and sorted out the professional opinions of doctors,pharmacists,and methodological experts,developed questionnaires and held two rounds of expert argumentation meetings,and finally screened out the most valuable results.The whole process management pathway of pharmaceutical care for breast cancer patients was formulated,and the referral principles of hospitals at different levels and the contents of pharmacist training and assessment were clarified.Results The whole process management pathway of pharmaceutical services for breast cancer patients was developed,including information collection,analysis,evaluation,development implementation of intervention plans,and follow-up.Conclusion This pharmaceutical service pathway can standardize and guide pharmacists in hospitals at different levels to carry out pharmaceutical services for breast cancer patients,achieve the whole process of monitoring drug use,and ensure rational drug use and treatment effectiveness for patients.

In January 2023,the American Heart Association(AHA)released A Scientific Statement:Cancer Therapy Related Hypertension,provided an overview of the mechanisms and clinical management of anticancer therapy related hypertension.Contemporary anticancer drugs are mostly at the expense of cardiovascular toxicities,one of the most common side effects is hypertension,especially vascular endothelial growth factor inhibitors,as well as tyrosine kinase inhibitors and proteasome inhibitors.Cancer therapy related hypertension is often dose limiting,and is usually reversible after interruption or discontinuation of treatment.The exact molecular mechanisms underlying hypertension are unclear,recent discoveries indicate an important role for decreased nitric oxide,increased endothelin-1,endothelial dysfunction,increased sympathetic outflow,and microvascular rarefaction.Based on the International Cardio Oncology Society(IC-OS),this article provides an interpretation of the diagnosis and management of hypertension related to cancer treatment.Insufficient evidence exists supporting an antihypertensive medication strategy specific to patients with anticancer therapy induced hypertension,therefore,antihypertensive management should follow current guidelines for the general population..Multidisciplinary cooperation is needed to optimize management to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.

Objective:To investigate the efficacy of Shuotong ureteroscope combined with flexible ureteroscope in the treatment of 2-3 cm lower calyceal calculi, and analyze the influencing factors.Methods:A total of 102 patients with lower calyceal calculi were treated in the Second People′s Hospital of Yulin from February 2019 to December 2022, and they were divided into the observation group and the control group, with 51 cases in each group. The patients of the observation group were treated with Shuotong ureteroscope combined with flexible ureteroscope, while the patients of the control group were treated with flexible ureteroscope. According to whether the stones were completely removed after operation, all patients were divided into non-stone removal group ( n=13) and stone removal group ( n=89). The operation time, hospitalization time, lithotripsy time, intraoperative blood loss, complication rate and stone clearance rate were compared between the observation group and the control group. Generalized Estimation Equation was used to analyze and evaluate the effects of treatment time, treatment scheme and their interaction on visual analogue scale (VAS), white blood cell (WBC), blood urea nitrogen (BUN), blood creatinine (Cr), hemoglobin (HGB) and procalcitonin (PCT). Univariate and multivariate Logistic regression were used to analyze the risk factors of stone removal rate. Nomogram model was constructed based on risk factors and evaluate the model. Results:Compared with the control group, operation time [(118.72±9.61) min vs (136.65±11.27) min], hospitalization stay [(6.43±1.12) d vs (10.29±2.23) d] and the lithotripsy time [ (51.23±10.38) min vs (56.62±11.43) min] of the observation group were shorter, and the amount of intraoperative blood loss [(128.52±10.20) mL vs (157.53±15.31) mL] were significantly less than those of the control group ( P< 0.05). The results of Generalized Estimation Equation analysis showed that treatment time, treatment regimen and their interaction had significant effects on WBC, HGB, BUN, Cr, PCT and VAS ( P< 0.05). Compared with the control group, the incidence of complications (5.88% vs 19.61%) of the observation group was lower and the stone clearance rate ( 94.12% vs 80.39%) was significantly higher than those in the control group ( P< 0.05). The mode of operation, infundibulopelvic angle(IPA), caliceal pelvic height (CPH) and the maximum diameter of stones were all influencing factors of stone removal rate in patients with 2-3 cm lower calyceal calculi. The nomogram model constructed in this study has good differentiation, calibration and clinical practicability, and can better identify high-risk patients with incomplete removal of 2-3 cm lower calyceal calculi. Conclusions:Shuotong ureteroscope combined with flexible ureteroscope is a safe, effective method for the treatment of 2-3 cm lower calyceal calculi. It has the advantages of simple operation, less intraoperative bleeding, less postoperative complications and high stone clearance rate. IPA, CPH, the maximum diameter of calculi and the mode of operation were all independent factors affecting the stone clearance rate of 2-3 cm lower calyceal calculi. The nomogram model constructed in this study can well identify the high-risk patients with incomplete clearance of 2-3 cm lower calyceal calculi.