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.

Objective: To investigate the factors affecting carotid plaques among perimenopausal women, so as to provide the basis for the prevention and early intervention of cardiovascular diseases in perimenopausal women. Methods: Perimenopausal women aged 40-60 who underwent health check-ups at Xingtai People's Hospital from January 2022 to January 2023 were selected as subjects by convenient sampling method. Demographic information, lifestyle, waist-to-hip ratio, and blood biochemical indicators were collected through questionnaire surveys, physical examinations, and laboratory tests. Carotid plaques were detected using a Doppler ultrasound diagnostic instrument. Factors affecting carotid plaques among perimenopausal women were identified using a multivariable logistic regression model. Results: Totally 2 146 perimenopausal women were surveyed, with an age of (50.04±5.82) years. Carotid plaques were detected in 525 cases, with a detection rate of 24.46%. Multivariable logistic regression analysis showed that older age (45-<50 years old, OR=1.474, 95%CI: 1.062-2.047; 55-60 years old, OR=1.779, 95%CI: 1.276-2.481), residing in urban areas (OR=1.601, 95%CI: 1.079-2.376), drinking (OR=1.805, 95%CI: 1.108-2.941), hypertension (OR=1.815, 95%CI: 1.290-2.553), abnormal waist-to-hip ratio (OR=2.479, 95%CI: 1.982-3.101), and abnormal atherogenic index of plasma (OR=1.325, 95%CI: 1.064-1.650) were associated with a higher risk of carotid plaques. College degree or above (college, OR=0.659, 95%CI: 0.502-0.865; bachelor's degree or above, OR=0.517, 95%CI: 0.397-0.673), physical exercise (OR=0.621, 95%CI: 0.494-0.781) were associated with a lower risk of carotid plaques. Conclusion The carotid plaques among perimenopausal women mainly affected by age, place of residence, educational level, alcohol consumption, physical exercise, hypertension, waist-to-hip ratio and atherogenic index of plasma.

Objective To explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P＜0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P＜0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Rice (Oryza sativa L.), as a thermophilic crop, is highly susceptible to cold stress during its growth process. Chilling injury at the plumule stage and seedling stage often affects the morphological development and leads to yield reduction of rice. The exploration and utilization of cold tolerance genes are among the most direct and effective approaches to address cold stress in rice. To identify quantitative trait loci (QTLs) associated with cold tolerance at plumule and seedling stages, in this study, we measured the seedling rates and survived seedling rates of the indica rice cultivar 'HZ', the japonica cultivar 'Nekken2', and their 120 recombinant inbred lines (RILs) under cold stress. A previously constructed high-density genetic linkage map was used for the mapping of the QTLs conferring cold tolerance at the plumule and seedling stages. A total of 4 QTLs for plumule-stage cold tolerance and 9 QTLs for seedling-stage cold tolerance were detected, with the maximum limit of detection reaching 5.20. Notably, a genetically overlapping QTL for both plumule and seedling stages was identified on chromosome 8, spanning a physical interval of 24 432 953-25 295 129 bp. Candidate genes within the detected QTL intervals were screened, and quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze the gene expression during the plumule and seedling stages. The results revealed that LOC_Os03g06570, LOC_Os03g07100, LOC_Os06g08280, LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540 exhibited significantly differential expression between the parental lines. These genes were either significantly downregulated or upregulated under cold stress. Among them, the first three gene (LOC_Os03g06570, LOC_Os03g07100, and LOC_Os06g08280) were hypothesized to be key candidates regulating the cold tolerance of rice seedlings, while the latter three genes (LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540) were identified as comprehensive regulators of cold tolerance during both plumule and seedling stages. These findings lay a foundation for the fine mapping and cloning of cold tolerance genes at the plumule and seedling stages, providing valuable insights for breeding cold-tolerant rice varieties.
Quantitative Trait Loci/genetics* ; Oryza/growth & development* ; Seedlings/growth & development* ; Cold Temperature ; Chromosome Mapping ; Gene Expression Regulation, Plant