Roxadustat is the world's first small molecule hypoxia-inducible factor prolyl hydroxylase inhibitor. Its adverse effect of causing hypothyroidism with low thyroid-stimulating hormone (TSH) is relatively rare and manifests subtly in elderly patients with multiple coexisting diseases. This article reports a case of an elderly patient with renal anemia who developed reversible low-TSH hypothyroidism after taking roxadustat for 12 days, with a significant decrease in thyroid hormone levels. After discontinuing roxadustat for 15 days, the thyroid hormone levels gradually returned to normal. Due to the worsening of renal anemia, the patient took roxadustat again, and 9 days later, the thyroid function-related indicators decreased upon re-examination, leading to the initiation of levothyroxine replacement therapy. In conjunction with relevant literature, this article analyzes the adverse reactions that occur during the oral administration of roxadustat in elderly patients with chronic kidney disease, aiming to provide reference for drug treatment of such patients.

ObjectiveTo investigate the inhibitory effect of Huoluo Xiaolingdan on triple negative breast cancer （TNBC） in mice through its regulation of TCF1⁺CD8⁺ stem cell-like T cells infiltration. MethodsA mouse model of TNBC was established and the mice were randomly divided into the model group， low-dose （3.9 g·kg^-1）， medium-dose （7.8 g·kg^-1） and high-dose （15.6 g·kg^-1） Huoluo Xiaolingdan groups， and anti-PD-1 antibody treatment group. Each group was given a dose of 0.01 mL·g^-1， while the model group and the anti-PD-1 treatment group were also given an equivalent volume of normal saline. The drug was administered for 21 days. In the anti-PD-1 antibody group， mice were intraperitoneally injected with 100 μg of mouse anti-PD-1 antibody twice a week， for a total of five injections. The tumor volume， survival time and tumor mass were measured at different time points. Hematoxylin-eosin （HE） staining was used to observe the histological changes of the tumor. The expression of CD8⁺T cells and TCF1⁺CD8⁺ stem-like T cells in tumor tissues was detected by immunohistochemistry and immunofluorescence staining. Flow cytometry was used to detect the difference of immune cell subsets in tumors and the expression difference of TCF1⁺CD8⁺ stem cell-like T cells in tumors and peripheral blood. The expression level of PD-L1 in tumor tissues was detected by Western blot. ResultsCompared with model group， the tumor volume and mass of in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group were decreased （P<0.05， P<0.01）. The median survival time of mice in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group was as follows： 27.00 days （95%CI， 0.45-2.65）， 31.00 days （95%CI， 0.32-1.89）， 34.00 days （95%CI， 0.40-2.33）， and 35.00 days （95%CI， 0.42-2.47）. All of them were higher than that of the model group ［24.50 days （95%CI， 0.37-10.5）］. Flow cytometry showed that compared with the model group， the proportion and number of infiltrating CD8⁺ T cells in tumor were increased in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group （P<0.05， P<0.01）， while the proportion of tumor regulatory T cells （Treg） and M2 macrophages decreased （P<0.05）. Compared with the model group， the proportion of IFN-γ⁺CD8⁺ T and GrzB⁺CD8⁺ T cells in tumors in low-， medium- and high-dose Huoluo Xiaolingdan groups and anti-PD-1 group was increased （P<0.01）， and the proportion of TCF1⁺CD8⁺ T cells in tumor and peripheral blood was also increased. Immunofluorescence staining further showed that the number of TCF1⁺CD8⁺ T cells in tumor tissues increased in low-， medium- and high-dose Huoluo Xiaolingdan groups. Western blot analysis showed no significant decrease in the PD-L1 protein expression in tumor tissues between the Huoluo Xiaolingdan groups and the model group. ConclusionHuoluo Xiaolingdan can inhibit TNBC in mice by increasing tumor infiltration of TCF1⁺CD8⁺ stem-like T cells， enhancing CD8⁺ T cell activity， and regulating immune cell subgroups such as M2 macrophages and Treg cells to enhance anti-tumor immunity. This study provides a theoretical basis for the clinical application of Huoluo Xiaolingdan in breast cancer treatment and combination therapy.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Objective: To analyze the characteristics and safety risks of preservatives and sweeteners in beverages sold near schools in Anshun City, so as to provide a evidence for formulating targeted regulatory strategies in campus. Methods: From December 2023 to July 2024, 834 beverage samples were collected from sales points near primary and secondary schools in Xixiu District and four surrounding townships of Anshun City by a stratified random sampling method. High performance liquid chromatography was used to detect three preservatives (sorbic acid, benzoic acid and dehydroacetic acid) and four sweeteners (sodium saccharin, acesulfame-K, aspartame, and neotame). Differences were analyzed using the Chi-square test. Results: The overall exceedance rate of preservative was 8.6% (72 samples), with dehydroacetic acid showing the highest exceedance rate (7.0%, 58 samples), significantly higher than sorbic acid (0.6%, 5 samples) and benzoic acid (0.4%, 3 samples) ( χ 2=90.85, P <0.01). The overall exceedance rate of sweetener was 10.4% (87 samples), with sodium saccharin having the highest exceedance rate ( 6.2 %, 52 samples),significantly higher than neotame (2.8%, 23 samples), acesulfame-K (0) and aspartame (0) ( χ 2=262.04, P <0.01). Potential risks were identified due to the co occurrence of multiple additive exceedances, including 0.7% (6 samples) for mixed preservatives and 1.6% (13 samples) for mixed sweetener. No statistically significant differences were found in preservative (7.2%, 26 samples) or sweetener (12.3%, 44 samples) exceedance rates between micro enterprises and large, medium and small enterprises ( χ 2=2.67, 5.16, both P >0.05). Conclusion Systemic misuse risk of food additives in beverages sold near school necessitates a risk traceability based regulatory framework, with emphasis on standardizing enterprise production practices and strengthening oversight of sales outlets near campuses.

BACKGROUND:The development of steroid-induced osteonecrosis of the femoral head is a complex process involving multiple mechanisms.There is still no standard therapeutic drug for early intervention of this disease.Current studies have shown that baicalein has various pharmacological activities such as regulating lipid metabolism,bone metabolism,apoptosis and anti-oxidative stress,which provides an idea for the prevention and treatment of steroid-induced osteonecrosis of the femoral head. OBJECTIVE:To observe the preventive effect of baicalein against steroid-induced osteonecrosis of the femoral head and to investigate its possible mechanism. METHODS:Thirty-six 10-week-old male Sprague-Dawley rats were randomly divided into three groups(n=12 per group):blank control group,model group,and baicalein intervention group.In the model group and baicalein intervention group,intraperitoneal lipopolysaccharide and intramuscular injection of methylprednisolone sodium succinate were performed for modeling,while normal saline was used as a substitute for the modeling drug in the blank control group.Baicalein 300 mg/kg was administered by gavage(once a day for 6 weeks)at the time of initial intramuscular glucocorticoid injection in the baicalein intervention group,and baicalein was replaced by normal saline in the other two groups.The serum level of malondialdehyde in rats was detected at 2 weeks of the experiment.Blood lipid indicators and bone formation metabolic markers were detected at 6 weeks of the experiment,the histomorphometric changes of the femoral head were analyzed by hematoxylin-eosin staining,anti-tartaric acid phosphatase staining and TUNEL staining,and the femoral head was subjected to Micro-CT scanning and three-dimensional reconstruction of the bone in order to analyze the alterations of bone tissue structure and parameters. RESULTS AND CONCLUSION:The serum levels of malondialdehyde,triglyceride,β-collagen type Ⅰ carboxy-terminal peptide were increased and the serum levels of bone specific alkaline phosphatase and pre-collagen type Ⅰ amino-terminal peptide were decreased in the model group compared with the blank control group(P＜0.05).The serum level of malondialdehyde decreased in the baicalein intervention group compared with the model group(P＜0.05),but there was no significant difference between the baicalein intervention group and blank control group(P＞0.05).The serum level of triglyceride was higher in the baicalein intervention group than the blank control group(P＜0.05),but had no significant difference between the baicalein intervention group and model group(P＞0.05).There were also no significant differences in the levels of bone specific alkaline phosphatase and β-collagen type Ⅰ carboxy-terminal peptide between the baicalein intervention group and the other two groups(P＞0.05).The serum level of the baicalein intervention group was lower in the baicalein intervention group than the blank control group(P＜0.05)but had no significant difference between the baicalein intervention group and model group(P＞0.05).Histomorphological analysis of the femoral head showed that the rate of bone empty lacuna,osteoclast counting and cell apoptosis rate in the femoral head of model group rats were significantly higher than those of the other two groups(P＜0.05).There was a significant increase in the number of adipocytes in the bone marrow cavity of the femoral head,bone trabeculae were thinned and sparsely arranged with more disruptions in the continuity.The incidence of osteonecrosis was higher in the model group(75%)than in the baicalein intervention group(25%;bilateral and unilateral exact significance results were both 0.05).There was also an increase in the number of adipocytes in the bone marrow cavity of the femoral head in the baicalein intervention group,and the trabecular changes were roughly similar to those in the model group.Micro-CT results showed that bone volume fraction,trabecular thickness,trabecular number,and bone mineral density decreased and trabecular separation increased in the model group compared with the blank control group(P＜0.05).Overall significant bone mass loss was observed in the model group.Bone tissue parameters in the baicalein intervention group were significantly improved than those in the model group,which were reflected in bone volume fraction,trabecular thickness and trabecular separation(P＜0.05),and trabecular number and bone mineral density had no significant difference between the baicalein intervention group and blank control group(P＞0.05).Although baicalein failed to significantly ameliorate dyslipidemia and promote bone formation in rats with steroid-induced osteonecrosis of the femoral head,it could reduce the incidence of steroid-induced osteonecrosis of the femoral head by reducing oxidative stress damage,decreasing cell apoptosis,inhibiting osteoclasts,suggesting its effectiveness in the early prevention of steroid-induced osteonecrosis of the femoral head.

To examine the global research trends and emerging focal points in the field ofgeriatric interdisciplinary team (GIT) from 2000 to 2023, so as to offer insights and reference for related research in China.

To investigate the collective influence of sarcopenia on the extended prognosis of hospitalized elderly individuals with type 2 diabetes mellitus(T2DM).

Objective: To explore the clinical application value of neural network technology,and to screen the clinical early warning indicators of severe hand-foot-mouth disease(HFMD) by constructing a back propagation neural network(BPNN) model. Methods: The clinical data of children with HFMD admitted to the Department of Infectious Diseases and Pediatrics of the First Affiliated Hospital of Xinxiang Medical University from January2019 to January 2023 were collected.The data were divided into 70% training samples and 30 % test samples using SPSS Modeler 18.0.The BPNN model and Logistic model were constructed to compare and evaluate the prediction accuracy and screening effect of the model. Results: The clinical data of 589 children were collected and analyzed,including 324 cases in the mild group and 265 cases in the severe group.The prediction accuracy of the test set(n=178) of BP neural network model and Logistic regression model was 82.02% and 84.83%,respectively.The area under the ROC curve(95% CI) was 0.791(0.749-0.834) and 0.625(0.577-0.674),respectively.Among the predictive variables output by the BPNN model,the top five factors that had the greatest impact on the grouping were highest body temperature,duration of fever,glutamyl transpeptidase,aspartate aminotransferase,and globulin.There were 3 of the top 10 overlaps in the importance of the predictive variables output by the two models,which were the highest body temperature,duration of fever and limb shaking. Conclusion The BPNN model and Logistic regression model perform well in screening and verifying the risk factors of severe hand-foot-mouth disease,but the comprehensive prediction performance of BP neural network model is better.The top five influencing factors of severe HFMD screened by the BPNN model are the highest body temperature,duration of fever,glutamyl transpeptidase,aspartate aminotransferase and globulin.

Objective:To report the long-term outcomes of Chinese rectal cancer patients after adopting a Watch and Wait (W&W) strategy following neoadjuvant therapy (NAT).Methods:This multicenter, cross-sectional study was based on real-world data. The study cohort comprised rectal cancer patients who had achieved complete or near complete clinical responses (cCRs, near-cCRs) after NAT and were thereafter managed by a W&W approach, as well as a few patients who had achieved good responses after NAT and had then undergone local excision for confirmation of pathological complete response. All participants had been followed up for ≥2 years. Patients with distant metastases at baseline or who opted for observation while living with the tumor were excluded. Data of eligible patients were retrospectively collected from the Chinese Wait-and-Watch Data Collaboration Group database. These included baseline characteristics, type of NAT, pre-treatment imaging results, evaluation of post-NAT efficacy, salvage measures, and treatment outcomes. We herein report the long-term outcomes of Chinese rectal cancer patients after NAT and W&W and the differences between the cCR and near-cCR groups.Results:Clinical data of 318 rectal cancer patients who had undergone W&W for over 2 years and been followed up were collected from eight medical centers (Peking University Cancer Hospital, Fudan University Shanghai Cancer Center, Sun Yat-sen University Cancer Center, Shanghai Changhai Hospital, Peking Union Medical College Hospital, Liaoning Cancer Hospital, the First Hospital of Jilin University, and Yunnan Cancer Hospital.) The participants comprised 221 men (69.4%) and 107 women (30.6%) of median age 60 (26-86) years. The median distance between tumor and anal verge was 3.4 (0-10.4) cm. Of these patients, 291 and 27 had achieved cCR or near-cCR, respectively, after NAT. The median duration of follow-up was 48.4 (10.2-110.3) months. The 5-year cumulative overall survival rate was 92.4% (95%CI: 86.8%-95.7%), 5-year cumulative disease-specific survival (CSS) rate 96.6% (95%CI: 92.2%-98.5%), 5-year cumulative organ-preserving disease-free survival rate 86.6% (95%CI: 81.0%-90.7%), and 5-year organ preservation rate 85.3% (95%CI: 80.3%-89.1%). The overall 5-year local recurrence and distant metastasis rates were 18.5% (95%CI: 14.9%-20.8%) and 8.2% (95%CI: 5.4%-12.5%), respectively. Most local recurrences (82.1%, 46/56) occurred within 2 years, and 91.0% (51/56) occurred within 3 years, the median time to recurrence being 11.7 (2.5-66.6) months. Most (91.1%, 51/56) local recurrences occurred within the intestinal lumen. Distant metastases developed in 23 patients; 60.9% (14/23) occurred within 2 years and 73.9% (17/23) within 3 years, the median time to distant metastasis being 21.9 (2.6-90.3) months. Common sites included lung (15/23, 65.2%), liver (6/23, 26.1%), and bone (7/23, 30.4%) The metastases involved single organs in 17 patients and multiple organs in six. There were no significant differences in overall, cumulative disease-specific, or organ-preserving disease-free survival or rate of metastases between the two groups (all P>0.05). The 5-year local recurrence rate was higher in the near-cCR than in the cCR group (41.6% vs. 16.4%, P<0.01), with a lower organ preservation rate (69.2% vs. 88.0%, P<0.001). The success rates of salvage after local recurrence and distant metastasis were 82.1% (46/56) and 13.0% (3/23), respectively. Conclusion:Rectal cancer patients who achieve cCR or near-cCR after NAT and undergo W&W have favorable oncological outcomes and a high rate of organ preservation. Local recurrence and distant metastasis during W&W follow certain patterns, with a relatively high salvage rate for local recurrence. Our findings highlight the importance of close follow-up and timely intervention during the W&W process.

Objective:The current study aimed to evaluate the possible protective effects of N-acetylcysteine (NAC) against Indum-tin oxide (ITO) nanoparticle (Nano-ITO) -induced pulmonary alveolar proteinosis (PAP) in rats, especially via modulation of nuclear factor kappa B (NF-κB) signaling.Methods:In October 2019, 50 adult male Sprague-Dawley rats were randomly allocated into five groups (10 rats each) as follows: blank control group, saline control group, NAC control group (200 mg/kg), Nano-ITO group (receiving a repeated intratracheal dose of 6 mg/kg Nano-ITO) and NAC intervention group (pre-treated intraperitoneally with 200 mg/kg NAC 1.5 h before the administration of an intratracheal dose of 6 mg/kg Nano-ITO). The rats were exposed twice a week for 12 weeks. Rats were then euthanized under anesthesia, and their lungs were removed for histopathological and immunohistochemical analysis. The comparison of indicators reflecting oxidative stress and pulmonary inflammation among groups was conducted using one-way analysis of variance (ANOVA) and Bonferroni's test. The effect of NAC on Nano-ITO induced NF-κB signaling pathway in rats was analyzed.Results:Histopathological examination of Nano-ITO exposed rats revealed diffuse alveolar damage, including PAP, cholesterol crystals, alveolar fibrosis, pulmonary fibrosis, and alveolar emphysema. Immunohistochemical results of Nano-ITO exposed rats showed strong positive for nuclear factor κB p65 (NF-κB p65) and nuclear factor Kappa B inhibitory factor kinase (IKK-β) and weak positive for nuclear factor κB inhibitory protein α (IκB-α) in the nuclei of bronchiolar and alveolar epithelial cells. Compared with blank control group, saline control group and NAC control group, the level of total protein (TP) in bronchoalveolar lavage fluid of rats in Nano-ITO group was significantly increased ( P<0.05), and the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) were significantly increased ( P<0.05), the levels of proinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were significantly increased ( P<0.05), and the levels of NF-κB p65, IKK-β, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) in lung tissue were significantly increased ( P<0.05). Compared with Nano-ITO group, the levels of TP, T-AOC, MDA and TNF-α in bronchoalveolar lavage fluid of rats in NAC intervention group were significantly decreased ( P<0.05), and the levels of NF-κB p65 and ROS in lung tissue were significantly decreased (P<0.05). Western blot results showed that compared with the control groups, the protein expressions of NF-κB p65 and IKK-β in the lung tissue of Nano-ITO group were increased, while the protein expression of IκB-α was decreased ( P<0.05). Compared with Nano-ITO group, the protein expressions of NF-κB p65 and IKK-β in lung tissue of rats in NAC intervention group were decreased, while the protein expression of IκB-α was increased ( P<0.05) . Conclusion:The study demonstrated that Nano-ITO might induce pulmonary toxicity through the activation of NF-κB signaling pathway, and NAC could antagonize the pulmonary toxicity of Nano-ITO by inhibiting the NF-κB signaling pathway.