ObjectiveTo analyze the epidemiological characteristics of patients with hepatitis C in Jinhua City, Zhejiang Province from 2005 to 2023, so as to provide a scientific basis for the prevention and control of hepatitis C. MethodsThe data on patients with hepatitis C, as well as whose current address is in Jinhua City, from 2005 to 2023 were collected from the infectious disease surveillance system of the China Disease Control and Prevention Information Management System. Descriptive epidemiological methods were used to analyze the temporal, spatial and demographic distribution characteristics of hepatitis C. ResultsA total of 2 326 cases of hepatitis C were reported in Jinhua from 2005 to 2023, including 2 death cases, with an average annual incidence rate of 2.19/100 000, showing a trend which rose first and then declined and then rose again. Hepatitis C was reported all the year round without significant seasonal pattern. In terms of the number of reported cases and the average annual incidence rate, Yiwu City ranked the first place. From 2005 to 2023, a total of 1 438 (61.82%) male cases and 888 (38.18%) female cases were reported, and the reported incidence rate was higher for males (2.62/100 000) than that for females (1.74/100 000), showing a statistically significant difference (χ²=92.937, P<0.001). Most cases aged between 30 to <50 years old (1 175, 50.52%), and the incidence rate of hepatitis C among the age group of 40‒<50, 50‒<60, 60‒<70 years old was showing an upward trend, with farmers (1 024, 44.02%) as the main occupation . ConclusionThe prevalence of hepatitis C in Jinhua City is generally at a low level, with an incidence rate of increasing and then decreasing, but rise up again after 2019. Therefore, epidemic surveillance and health education among the male, middle-aged and elderly people and farmers, as well as the key regions where the migrant workers flows in should be enhanced.

Objective To investigate the association between the pattern of carotid artery calcification and the prognosis of patients with acute cerebral infarction after 3 months of treatment. Methods A total of 112 patients who were diagnosed with acute ischemic stroke （AIS） in our hospital from March 2021 to September 2022 were enrolled as subjects. CT angiography was performed within 24 hours after admission， and the carotid artery was assessed in terms of calcification pattern （no calcification， intimal calcification， and medial calcification） and calcification load （low and high calcification）. After 7 days of treatment， CT reexamination was performed to evaluate hemorrhagic transformation and infarct volume. The patients were followed up for 3 months， and according to the modified Rankin Scale （mRS） score， they were divided into good prognosis group （82 patients with an mRS score of <3 points） and poor prognosis group （30 patients with an mRS score of ≥3 points）. Results Compared with the good prognosis group， the poor prognosis group had a significantly higher proportion of patients with an age of ≥70 years， a mean systolic blood pressure of ≥165 mmHg， a fasting blood glucose level of ≥7.5 mmol/L， an NIHSS score of ≥12 on admission， intimal calcification， medial calcification， high calcification， hemorrhagic transformation， and an infarct volume of ≥50 mm3 （P<0.05）. The multivariate logistic regression analysis showed that NIHSS score ≥12 on admission， intimal calcification， hemorrhagic transformation， and infarct volume ≥50 mm3 were risk factors for poor prognosis （P<0.05）. Conclusion Intimal calcification of the carotid artery may be associated with the poor short-term prognosis of AIS patients， which can be used as a new noninvasive indicator for predicting prognosis.
Prognosis

OBJECTIVE To investigate the absorption characteristics and tissue distribution of silybin （Sy） nanocrystals prepared by two methods in different intestinal segments of rats. METHODS Sy nanocrystals （i.e. Sy-NS-G and Sy-NS-F） with comparable particle sizes were prepared using high-pressure homogenization and anti-solvent precipitation methods， respectively. Rats were randomly divided into three groups： Sy raw drug group， Sy-NS-G group， and Sy-NS-F group. Each group was further divided into three subgroups with low， medium， and high （60， 120， 180 μg/mL） mass concentrations （calculated based on Sy）， with 3 rats in each subgroup. The absorption rate constant （Ka） and apparent absorption coefficient （Papp） of Sy raw drug， Sy-NS-G and Sy-NS-F in different intestinal segments were investigated by using the in vivo one-way intestinal perfusion experiment. Additionally， the rats were divided into three groups: Sy raw drug group， Sy-NS-G group， and Sy-NS-F group， with 20 rats in each group. Rats in each group were administered a single intragastric dose of 50 mg/kg （calculated based on Sy）. They were sacrificed at 0.3， 1， 4， 10， and 24 hours post-administration respectively， to investigate the tissue distribution of Sy raw drug， Sy- NS-G， and Sy-NS-F in the heart， liver， spleen， lungs， kidneys， brain and intestines. RESULTS In duodenum and jejunum， the Ka and Papp of the nanocrystals prepared by the two methods remained unchanged with the increase of Sy concentration， and there was no significant difference （P＞0.05）； the absorption of Sy-NS-F in the duodenum was greater than that of Sy-NS-G； the absorption sites of Sy-NS-G and Sy raw drug were mainly in the ileum， while those of Sy-NS-F were mainly in the duodenum and ileum. The concentrations of Sy-NS-G and Sy-NS-F in different tissues of rats were different； Sy-NS-G peaked in most tissues at 1 h， and the distribution concentration was as follows： intestine＞spleen＞heart＞lungs＞liver≈brain＞kidneys. Sy-NS-F reached its peak at 1 h， and the distribution concentration was in the order of intestine＞spleen＞kidney＞lung＞heart≈liver＞brain. CONCLUSIONS The absorption mode of Sy nanocrystals in the duodenum and ileum is mainly passive diffusion. In the duodenum， the absorption of Sy-NS-F is greater than that of Sy-NS-G； there are significant differences in the tissue distribution of Sy-NS-G and Sy-NS-F in rats.

ObjectiveTo explore the role and potential mechanism of circulating glutamate in enhancing insulin sensitivity by aerobic exercise. This research may provide a novel strategy for preventing metabolic diseases through precise exercise interventions. MethodsTo investigate the effects of elevated circulating glutamate on insulin sensitivity and its potential mechanisms, 18 male C57BL/6 mice aged 6 to 8 weeks were randomly divided into 3 groups: a control group (C), a group receiving 500 mg/kg glutamate supplementation (M), and a group receiving 1 000 mg/kg glutamate supplementation (H). The intervention lasted for 12 weeks, with treatments administered 6 d per week. Following the intervention, an insulin tolerance test (ITT) and a glucose tolerance test (GTT) were conducted. Circulating glutamate levels were measured using a commercial kit, and the activity of the skeletal muscle InsR/IRS1/PI3K/AKT signaling pathway was analyzed via Western blot. To further investigate the role of circulating glutamate in enhancing insulin sensitivity through aerobic exercise, 30 male C57BL/6 mice were randomly assigned to 3 groups: a control group (CS), an exercise intervention group (ES), and an exercise combined with glutamate supplementation group (EG). The ES group underwent treadmill-based aerobic exercise, while the EG group received glutamate supplementation at a dosage of 1 000 mg/kg in addition to aerobic exercise. The intervention lasted for 10 weeks, with sessions occurring 6 d per week, and the same procedures were followed afterward. To further elucidate the mechanism by which glutamate modulates the InsR/IRS1/PI3K/AKT signaling pathway, C2C12 myotubes were initially subjected to graded glutamate treatment (0, 0.5, 1, 3, 5, 10 mmol/L) to determine the optimal concentration for cellular intervention. Subsequently, the cells were divided into 3 groups: a control group (C), a glutamate intervention group (G), and a glutamate combined with MK801 (an NMDA receptor antagonist) intervention group (GK). The G group was treated with 5 mmol/L glutamate, while the GK group received 50 μmol/L MK801 in addition to 5 mmol/L glutamate. After 24 h of intervention, the activity of the InsR/IRS1/PI3K/AKT signaling pathway was analyzed using Western blot. ResultsCompared to the mice in group C, the circulating glutamate levels, the area under curve (AUC) of ITT, and the AUC of GTT in the mice of group H were significantly increased. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle were significantly downregulated. Compared to the mice in group CS, the circulating glutamate levels, the AUC of ITT, and the AUC of GTT in the mice of group ES were significantly reduced. Additionally, the expression levels of p-InsRβ, IRS1, p-AKT, and p-mTOR proteins in skeletal muscle of group ES mice were significantly upregulated. There were no significant changes observed in the mice of group EG. Compared to the cells in group 0 mmol/L, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in cells of group 5 mmol/L were significantly downregulated. Compared to the cells in group C, the expression levels of p-InsRβ, p-IRS1, p-PI3K, and p-AKT proteins in the cells of group G were significantly downregulated. No significant changes were observed in the cells of group GK. ConclusionLong-term aerobic exercise can improve insulin sensitivity by lowering circulating levels of glutamate. This effect may be associated with the upregulation of the InsR/IRS1/AKT signaling pathway activity in skeletal muscle. Furthermore, glutamate can weaken the activity of the InsR/IRS1/PI3K/AKT signaling pathway in skeletal muscle, potentially by binding to NMDAR expressed in skeletal muscle.

Pulmonary endometriosis (PEM) is a rare disease with diverse clinical manifestations, most commonly presenting as hemoptysis, while patients presenting solely with pulmonary nodules are less common. Here, we report three female patients (aged 32, 19, and 46 years, respectively). One patient sought medical attention due to hemoptysis during menstruation, while the other two had no obvious symptoms and were found to have pulmonary nodules during routine physical examinations. Two patients had a history of cesarean section, and one had a history of miscarriage. Pathologically, one patient of PEM showed extensive hemorrhage in the alveolar spaces, with fragmented endometrial glandular epithelium observed within the hemorrhagic foci. The other two patients exhibited proliferative endometrial glands and stroma, surrounded by old hemorrhage. Immunohistochemistry revealed that the endometrial glands and stroma in all three patients were positive for estrogen receptor, progesterone receptor, and vimentin, with CD10 positivity in the endometrial stroma. All three patients were definitively diagnosed as PEM by pathology and underwent thoracoscopic pulmonary wedge resection. Follow-up periods were 18, 31, and 49 months, respectively, with no recurrence observed in any of the patients.

Objective To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in elderly hypertensive population. Methods Elderly physical examination population who received dual-energy bone mineral density examination and bone metabolic marker test in the hospital were selected from January 2021 to December 2024. According to whether they had hypertension and dual-energy bone mineral density results, the enrolled patients were divided into hypertension OP group (142 cases ), hypertension non-OP group (173 cases), non-hypertension OP group (102 cases) and non-hypertension non-OP group (100 cases). GNRI of all study subjects was measured. The correlation of GNRI and the occurrence of OP was explored by logistic regression analysis. The predictive efficiency of GNRI on the occurrence of OP was evaluated by receiver operating characteristic (ROC) curve. Results The BMD and GNRI in the hypertension group, and the non-hypertension OP group were significantly lower than those in the non-hypertension non-OP group (P<0.05). Compared with the hypertension non-OP group, the BMI, GNRI, BMD, and 25-OH Vit D in the hypertension OP group were significantly reduced (P<0.05) while the PTH level was significantly enhanced (P<0.05).logistic regression analysis showed that GNRI, 25-OH Vit D and PTH were closely related to OP in the elderly hypertensive population (P < 0.05). ROC curve analysis manifested that the AUC value of GNRI alone in predicting OP in elderly hypertensive population was 0.802, which was higher than that of 25-OH Vit D (AUC=0.723) and PTH (AUC=0.643). The AUC, sensitivity and specificity of combination of GNRI, 25-OH Vit D and PTH in predicting OP in elderly hypertensive population were 0.837, 66.20% and 86.13% (P<0.05). Conclusion GNRI is closely related to the occurrence of OP in elderly hypertensive population, and GNRI can be used as a potential indicator to assess the risk of OP.

Non-small cell lung cancer （NSCLC）， as the most common subtype of lung cancer， has a high incidence and mortality rate among global cancer cases. Although modern medicine has made remarkable progress in the treatment of NSCLC with advances in screening technologies and continuous optimization of therapeutic regimens， current treatments inevitably result in adverse outcomes such as high tumor recurrence rates， significant toxic side effects， and poor quality of life for patients. Traditional Chinese medicine （TCM） holds that the core pathogenesis of lung cancer lies in ''deficiency of healthy Qi and excess of pathogenic factors''. It originates from congenital insufficiency or acquired malnourishment， leading to an imbalance of Yin and Yang， deficiency of healthy Qi， and inability to eliminate pathogenic factors. The interactions among Qi stagnation， phlegm accumulation， blood stasis， and toxins give rise to disease. The root is deficiency， while the manifestation is excess. Therefore， the treatment of lung cancer in TCM is generally guided by the principle of "supporting the healthy Qi and eliminating the pathogens". A large number of clinical and pharmacological studies have shown that TCM and its active components can， through multiple targets and mechanisms， alleviate postoperative and chemoradiotherapy-related adverse reactions， inhibit tumor growth and recurrence， and improve the quality of life of patients with NSCLC. It is worth noting that although extensive studies have been conducted on the therapeutic patterns and pharmacological mechanisms of TCM and its active substances in NSCLC treatment， issues such as the diversity of medicinal materials， the complexity of chemical components， the scientific basis of herbal compatibility， and the flexibility of dosage indicate that there is still considerable room for further clinical and basic research. This review summarizes recent literature on the clinical syndromes， drug selection， medication patterns， and pharmacological mechanisms of TCM and its active components in the treatment of NSCLC， aiming to provide guidance for clinical medication in TCM therapy for NSCLC and to deepen the understanding and research of its therapeutic mechanisms.

Objective To establish the drug use evaluation(DUE)standard of bivalirudin for injection,and to evaluate the use of the drug by weighted TOPSIS method,so as to provide a reference for rational use of bivalirudin.Methods Based on the package insert,clinical guidelines and consensus of experts of bivalirudin,the DUE standards were developed,and the weighted TOPSIS method was used to evaluate the rationality of the discharge medical records of Shanxi Bethune Hospital from January 1st to June 30th in 2022.Results Incorporating 108 medical records involving the use of bivalirudin for injection,88 cases(81.48％)exhibited a high degree of adherence(Ci≥0.8)between the prescribed drug regimens and the optimal recommendations,which is considered reasonable.Additionally,19 cases(17.59％)fell within the range of 0.6＜Ci＜0.8,indicating a generally reasonable adherence.Only one case(0.93％)had a Ci＜0.6,suggesting an unreasonable level of adherence.The irrational situations about various evaluation indicators in the DUE were mainly manifested in the inappropriate dosages of administration(12.04％),inappropriate disposal of adverse reactions(11.11％),using medicine with contraindications(3.70％),using medicine without indication(1.85％),inappropriate monitoring of adverse reactions(0.93％),etc.Conclusion The established DUE standards for bivalirudin are intuitive and comprehensive,and the evaluation results show that there are some unreasonable situations in the use of bivalirudin in the hospital,and it is necessary to standardize the use of bivalirudin in terms of dosages,disposal of adverse reactions,indication and contraindication.

Objective To establish the drug use evaluation(DUE)criteria of recombinant human prourokinase(rhPro-UK),and to provide reference for the rational clinical application of rhPro-UK.Methods Based on the drug instructions of rhPro-UK,DUE standard rules were established by referring to relevant guidelines,expert consensus,authoritative literature and expert consultation.The medical records of hospitalized patients treated with rhPro-UK from January 2019 to May 2022 in Xilin Gol League Central Hospital were evaluated by retrospective investigation.The effectiveness of rhPro-UK was evaluated based on clinical outcome,and its safety was evaluated based on the incidence and severity of adverse reactions.Results A total of 230 cases were included,and 4 cases fully met the evaluation criteria(medication indication,medication process,medication results),accounting for 1.74％.There were 226 patients(98.26％)with irrational drug use,mainly manifested in two aspects of drug indication and drug process(administration mode and dosage).Treatment was effective in 221 patients,with an overall effective rate of 96.09％;139 patients experienced adverse reactions,with an incidence rate of 60.43％.Conclusion The clinical use of rhPro-UK in our hospital is irrational in the indication of medication and the process of medication,and the establishment of the DUE standard rules of rhPro-UK can provide a reference to standardize the clinical application of rhPro-UK and promote its rational use.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.