OBJECTIVE To analyze the occurrence characteristics and risk factors of adverse drug reactions （ADR） of gemcitabine for injection in national centralized volume-based procurement （hereinafter referred to as “centralized procurement”）， and provide reference for clinical safe drug use. METHODS A retrospective study was conducted to collect the relevant case reports of gemcitabine for injection reported to the National Adverse Drug Reaction Monitoring System by Inner Mongolia Autonomous Region from January 2022 to December 2023； basic information of patients， drug use status， patient outcomes， rational drug use and other information were collected， and the occurrence characteristics of ADRs with leukopenia， myelosuppression， neutropenia， thrombocytopenia and liver dysfunction were analyzed. Univariate analysis and multivariate Logistic regression were used to analyze the correlation of gender， age， combination of antitumor drugs， original malignant tumor and drug dose with ADR. RESULTS A total of 315 cases reports （315 patients） of gemcitabine-induced ADR were included in this study， with a male-to-female ratio of 1.42∶1 and age of （61.17±9.13） years. The primary malignant tumor was pancreatic cancer （73 cases， 23.17%）. Leukopenia， myelosuppression and nausea were the most common ADR， followed by neutropenia， thrombocytopenia， liver dysfunction and so on. The severity grade of ADR was mainly 1-2， and the outcome of most ADR was good. Multivariate Logistic regression analysis showed that combination of antitumor drugs was a risk factor for myelosuppression and neutropenia （RR＝2.154， 95%CI： 1.218- 3.807， P＝0.008； RR＝3.099， 95%CI： 1.240-7.744， P＝0.016）； gender （female） was a risk factor for leukopenia and liver dysfunction （RR＝0.508， 95%CI： 0.302-0.853， P＝0.010； RR＝0.301， 95%CI： 0.102-0.887， P＝0.029）. In terms of drug use rationality， there were 143 cases （45.40%） of drug 126.com use in accordance with the indications of the label， and 172 cases （54.60%） of off-label drug use. Among them， the primary malignant tumors were bladder cancer， bile duct cancer and ovarian cancer， which ranked the top three off-label drug use. CONCLUSIONS The ADR caused by gemcitabine in Inner Mongolia is mainly in the blood and digestive systems. The severity of ADRs is mainly classified as 1-2 levels， and most ADRs have good outcomes. Gender （female） and combination medication are risk factors for gemcitabine-induced ADR. Appropriate chemotherapy regimen should be selected according to the patient’s condition and physical condition， and ADR monitoring in blood and digestive systems should be strengthened during medication of gemcitabine.

OBJECTIVE To investigate the effects of parthenolide （PLT） on systemic inflammation and intestinal injury in rats with acute pancreatitis （AP） by regulating the Kelch-like epichlorohydrin-associated protein 1 （Keap1）/nuclear factor-erythroid-2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. METHODS AP rat model was established by injecting 3.5% sodium taurine cholate solution （1 mL/kg） into the biliary pancreatic duct， and modeled rats were divided into AP group， PLT （300 µg/kg） group， dexamethasone （2 mg/kg） group， inhibitor （11 mg/kg Nrf2 inhibitor ML385） group， and PLT+inhibitor group （300 µg/kg PLT+11 mg/kg ML385）， with 10 rats in each group. Another 10 rats were taken as a sham operation group. Each group was given relevant medicine or normal saline via tail vein/intraperitoneal injection once. After 24 h， serum lipase and amylase levels， the levels of oxidative stress index [superoxide dismutase （SOD） and malondialdehyde （MDA）] and inflammatory factors [interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α）] were detected. The histopathological changes in colon mucosa and pancreas were observed， and Chiu and Schmidt scores were performed. The cell apoptosis in colon mucosa and the protein expressions of Keap1， Nrf2 and HO-1 were detected. RESULTS Compared with the sham operation group， there was obvious inflammatory cell infiltration in colon mucosa and pancreatic tissue， cell shedding or tissue necrosis and severe bleeding； serum levels of lipase， amylase， MDA， IL-1β， IL-6 and TNF-α， Chiu and Schmidt scores， apoptotic rate and protein expression of Keap1 in colonic mucosa were significantly increased or up-regulated， while SOD level and protein expressions of Nrf2 20230993） and HO-1 were decreased or down-regulated significantly （P＜0.05）. Compared with the AP group， the above indexes in the PLT group and dexamethasone group were significantly improved， while those in the inhibitor group further deteriorated （P＜0.05）. Inhibitor could significantly reverse the improvement effect of PLT on the above indexes in AP rats （P＜ 0.05）. CONCLUSIONS PLT inhibits inflammation and oxidative stress in AP rats， alleviates intestinal damage， and its mechanism may be related to inhibiting protein expression of Keap1 and activating Nrf2/HO-1 signaling pathway.

OBJECTIVE To evaluate the cost-effectiveness of vitamin D analogue for postmenopausal osteoporotic women in China. METHODS A Markov microsimulation model was developed to analyze the clinical and economic outcomes of eldecalcitol， alfacalcidol and calcitriol for postmenopausal osteoporosis from the healthcare system perspective in China. The clinical parameters required for the model were derived from network meta-analysis， while cost and utility data were primarily obtained from the literature. The cycle length was 1 year ， the time horizon was life time， and the willingness-to-pay threshold was 0.5 times the gross domestic product per capita in China in 2023（44 679 yuan/QALY）. Model uncertainty was tested with one-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis. RESULTS The quality-adjusted life years （QALYs） for eldecalcitol were calculated to be 12.03 QALYs， which were higher than those for alfacalcidol （11.94 QALYs） and calcitriol （11.92 QALYs）. Meanwhile， the direct medical cost associated with eldecalcitol treatment amounted to 38 805 yuan， which was lower than that of alfacalcidol （45 173 yuan） and calcitriol （45 821 yuan）. The results of the one-way sensitivity analysis showed that the risk ratio of hip fracture and vertebral fracture had a significant impact on the result. The probabilistic sensitivity analysis and scenario analysis showed the robustness of the findings from the base-case analysis. CONCLUSIONS Compared with alfacalcidol and calcitriol， eldecalcitol is likely to be a cost-effective treatment for postmenopausal osteoporotic women in China.

To analyze the distribution of serotypes and antimicrobial resistance of clinical Salmonella isolates from multiple centers across China.

ObjectiveTo establish a polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method for rapid distinguishing Periplocae Cortex from Acanthopanacis Cortex and Lycii Cortex， so as to avoid the influence of genetic confusion on drug safety. MethodThe DSS-tagged sequences of Periplocae Cortex were obtained from the Chloroplast Genome Information Resource （CGIR） and analyzed to find the enzymatic cleavage sites that were different from those of Acanthopanacis Cortex and Lycii Cortex. The specific enzymatic cleavage site， Cla I， of Periplocae Cortex was selected， on the basis of which the primers for PCR-RFLP were designed. Furthermore， the factors such as annealing temperature， number of cycles， Taq enzyme， PCR instruments， and enzymatic treatment time that may influence PCR-RFLP were studied. The established PCR-RFLP method was applied to the identification of Periplocae Cortex， Acanthopanacis Cortex， and Lycii Cortex samples produced in different regions. ResultThe PCR-RFLP at the annealing temperature of 59 ℃ and with 40 cycles showed clear bands of the samples. When the enzyme digestion time was 30 min. The reaction produced the target bands at about 140 bp and 290 bp for both Periplocae Cortex and its original plant and only a band at about 430 bp for Acanthopanacis Cortex， Lycii Cortex， and their original plants. The method can accurately distinguish Periplocae Cortex from its confounders Acanthopanacis Cortex and Lycii Cortex. ConclusionThe PCR-RFLP method for distinguishing Periplocae Cortex from Acanthopanacis Cortex and Lycii Cortex was established. It has high stability， sensitivity， and applicability， providing a reference for the quality control of Periplocae Cortex， Acanthopanacis Cortex， and Lycii Cortex.

The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.

ObjectiveTo investigate the effect of Fuzheng Huayu prescription on hepatocyte extinction and regeneration in fibrotic liver and its mechanism of action in promoting hepatocyte regeneration. MethodsMice were given intraperitoneal injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and there were 10 mice in the model group， 10 in the sorafenib group， 10 in the Fuzheng Huayu prescription group， and 9 in the normal control group. Since week 4 of modeling， the mice in the Fuzheng Huayu prescription group and the sorafenib group were given the corresponding drug by gavage at a dose of 4.8 g/kg and 4 mg/kg， respectively， for three consecutive weeks， and those in the normal group and the model group were given an equal volume of sodium carboxymethyl cellulose. Serum liver function parameters were measured； the METAVIR scoring system was used to evaluate liver inflammation and fibrosis stage； Sirius Red staining and hydroxyproline （Hyp） content in liver tissue were used to evaluate collagen deposition； immunohistochemistry was used to measure the protein expression levels of type IV collagen， CD31， CD32b， Ki67， CyclinD1， glutamine synthetase， Wnt2， and HGF， and Western blot was used to measure the expression levels of Wnt2， LRP6， β-catenin， p-β-catenin， and CyclinD1 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group， the Fuzheng Huayu prescription group and the sorafenib group showed the following changes： significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of Hyp in liver tissue （all P<0.01）； a significant reduction in METAVIR score； significant reductions in the expression levels of type Ⅳ collagen and CD31 （all P<0.05） and a significant increase in the expression level of CD32b （P<0.01）； significant reductions in the number of parenchymal extinction lesions and significant increases in the expression levels of Ki67 and CyclinD1 in liver tissue （all P<0.01）； significant increases in the protein expression levels of Wnt2， LRP6， β-catenin， and CyclinD1 and a significant reduction in the protein expression level of p-β-catenin （all P<0.05）； significant increases in the number of cells stained positive for both CD32b and Wnt2. ConclusionFuzheng Huayu prescription can inhibit hepatic sinusoidal capillarization， improve the Wnt2 exocrine function of liver sinusoidal endothelial cells， activate the Wnt/β-catenin signaling pathway associated with hepatocyte regeneration， and finally reverse liver cirrhosis.

Inflammatory bowel disease （IBD）， mainly including ulcerative colitis （UC） and Crohn's disease （CD）， is a common chronic inflammatory disease of the gastrointestinal tract， with its incidence increasing year by year. Due to its long treatment duration， difficulty in treatment， prolonged remission， and high costs， it has attracted global attention. Exploring safe， effective， and sustainable treatment regimens has become an urgent global issue. The pathogenesis of IBD is complex， involving intestinal mucosal injury，disturbances in the internal environment， and inflammatory responses. In recent years， research has found that ferroptosis is also one of the important pathogenic factors of IBD. Ferroptosis， as a new form of non-apoptotic cell death， is characterized by iron dependence， lipid peroxidation， and imbalance in the redox system. Studies have shown that inhibiting ferroptosis in intestinal epithelial cells can protect the intestinal mucosa. Targeted intervention in ferroptosis may be a new direction for the treatment of IBD. IBD is mainly treated with drugs， including corticosteroids， aminosalicylates， biologics， and immunomodulators， but drug resistance and adverse reactions are common. Traditional Chinese medicine （TCM） has unique advantages such as low cost， low drug resistance， and fewer side effects， and has accumulated rich experience in the treatment of IBD. Scholars have confirmed that TCM can inhibit ferroptosis， and recent studies have shown that TCM can not only inhibit iron-dependent lipid peroxidation in intestinal cells but also enhance the antioxidant and anti-inflammatory abilities of intestinal mucosa， thus playing a role in the treatment of IBD. Increasing evidence suggests that TCM may treat IBD by interfering with ferroptosis. This article explores the relevance of TCM intervention in ferroptosis and the treatment of IBD， discusses the possible mechanisms of ferroptosis in IBD， and aims to provide a basis for the diagnosis and treatment of IBD.

As a classic prescription for invigorating spleen and replenishing qi, Sijunzi Decoction has a good clinical efficacy in the treatment of gastric cancer. It can improve chemotherapy resistance, reduce the toxic and side effects of chemotherapy, promote postoperative recovery, enhance immunity, improve the nutritional status of patients, improve the quality of life of patients and prevent precancerous lesions. Network pharmacology studies have shown that Sijunzi Decoction exerts anti-gastric cancer effects through multiple active ingredients, multiple targets and multiple pathways, and quercetin may be the main active component in Sijunzi Decoction to exert anti-gastric cancer effects. The main mechanisms of Sijunzi Decoction in the treatment of gastric cancer include regulating the expression of cell cycle and apoptosis-related gene proteins, and inhibiting the proliferation, migration, invasion and gastric cancer stem cell characteristics of gastric cancer cells.

Objective To discuss the safety and efficacy of arterial embolization combined with local ablation in the treatment of recurrent and refractory chest wall tumors.Methods The clinical data of 11 patients with chest wall tumor that recurred after surgery and progressed after treatment were retrospectively analyzed.On the basis of the original treatment regimen,DSA-guided arterial embolization and CT-guided local ablation were employed.VAS score of pain relief and postoperative complications were recorded,and the therapeutic efficacy was evaluated Results All the patients were follow up for a median time of 18.5 months.Successful DSA-guided arterial embolization was accomplished in all patients.Seven patients(9 lesions in total)initially received CT-guided radiofrequency ablation(RFA),and tumor reoccurred in 2 patients,who had to receive RFA once more.Four patients(5 lesions in total)initially received CT-guided microwave ablation(MWA),and tumor reoccurred in one patient,who had to receive MWA again.According to mRECIST criteria,the 6-month,12-month and 18-month objective response rates(ORR)were 72.7%(8/11),45.5%(5/11)and 18.2%(2/11)respectively,the 6-month,12-month and 18-month overall survival rates were 81.8%(9/11),63.6%(7/11)and 27.3%(3/11)respectively,with a median survival time of 13.2 months.The postoperative one-month and 3-month VAS scores were(2.42±1.25)points and(1.91±1.24)points respectively,which were strikingly lower than preoperative(6.78±1.13)points,the differences were statistically significant(P＜0.05).After surgery,3 patients developed pleural effusion,which disappeared after puncture and drainage treatment,and 2 patients developed fever,which was improved after symptomatic treatment.One patient died of respiratory failure six months after treatment.Conclusion Arterial embolization combined with local ablation can improve the symptoms of pain and prolong the survival time of patients with chest wall tumors.This combination therapy is less traumatic and clinically safe,and it can be used as an effective treatment for patients with recurrent and refractory chest wall tumors.