OBJECTIVE To conduct a clinical comprehensive evaluation of five marketed thrombopoietin receptor agonists （TPO-RA） approved in China， providing quantitative evidence for drug selection and therapeutic decision-making in medical institutions. METHODS Relevant data on Romiplostim for injection， Eltrombopag olamine tablets， Herombopag olamine tablets， Avatrombopag maleate tablets， and Lusutrombopag tablets were collected. Based on the Chinese Rapid Guide for Drug Evaluation and Selection in Medical Institutions （Second Edition）， 12 formulations of these five TPO-RA were scored quantitatively and comparatively across five dimensions： pharmacological characteristics， efficacy， safety， cost-effectiveness， and other attributes. RESULTS The comprehensive scores of the 12 formulations ranged from 62.56 to 75.50 points， with most scoring ≥70 points. Using the highest-scoring formulation for each generic name as a representative， the overall rankings of the five TPO-RA were as follows： Lusutrombopag tablets （75.50 points）， Eltrombopag olamine tablets （75.10 points）， Avatrombopag maleate tablets （70.40 points）， Romiplostim for injection （63.93 points）， and Herombopag olamine tablets （63.52 points）. Lusutrombopag tablets scored relatively high in pharmacological characteristics， safety， and cost-effectiveness， while Eltrombopag olamine tablets performed well in efficacy and cost-effectiveness. The other formulations showed varying scores across evaluation dimensions. CONCLUSIONS The five TPO-RA demonstrate favorable overall clinical value， with Lusutrombopag tablets and Eltrombopag olamine tablets ranking higher in comprehensive scores， these two drugs should be prioritized in drug selection and formula optimization by medical institutions.

Objective To assess the current status of microbial and parasitic quality control for laboratory animals in Jiangxi Province by analyzing microbiological and parasitic test results from production facilities between 2020 and 2024, and to provide a basis for enhancing quality control measures. MethodsIn accordance with the current national standards for laboratory animals at the time of testing, the Jiangxi Provincial Laboratory Animal Quality Inspection Station (affiliated to Institute of Occupational Medicine of Jiangxi) conducted microbial and parasitic testing on 451 laboratory animals of 4 species from 6 laboratory animal production units in Jiangxi Province between 2020 and 2024, and analyzed the quality status of laboratory animals in the province. ResultsPasteurella pneumotropica was detected in one mouse sample in 2020, with a detection rate of 5.00%. Pseudomonas aeruginosa was detected in one mouse sample and mouse hepatitis virus antibody was detected in another mouse sample in 2023, with a detection rate of 2.78%, respectively. No microorganisms or parasites that should be excluded from SPF grade mice as specified in the national standards were detected in 2021, 2022, or 2024, with a qualification rate of 100.00%. Pasteurella pneumotropica was detected in four rat samples in 2020, with a detection rate of 20.00%. Pseudomonas aeruginosa was detected in two rat samples in 2021, with a detection rate of 10.00%, and Tyzzer's disease agent antibody was detected in four rat samples in 2024, with a detection rate of 10.00%. No microorganisms or parasites that should be excluded from SPF grade rats as specified in the national standards were detected in 2022 or 2023, with a qualification rate of 100.00%. For rabbits and guinea pigs, no microorganisms or parasites required to be tested for conventional grade rabbits and guinea pigs as specified in the national standards were detected from 2020 to 2024, with the qualification rate of both species reaching 100.00%. ConclusionBased on the microbial and parasitic testing results, the quality of rabbits and guinea pigs in Jiangxi Province is satisfactory. However, some issues persist with rats and mice. It is recommended to enhance the quality of experimental animals in Jiangxi Province by increasing the frequency of random inspections by quality testing units or by improving the self-inspection capabilities of production and user facilities.

ObjectiveTo determine whether Jinshui Huanxian component formula Ⅱ （ECC-JHF Ⅱ） and matrix hardness interfere with the process of epithelial-mesenchymal transition （EMT） during pulmonary fibrosis by regulating integrin β₁ （ITG β₁）， and to elucidate the underlying mechanism. MethodsA pulmonary fibrosis mouse model was established by a single intratracheal instillation of bleomycin （BLM）. To observe the disease progression at various time points， the mice were sacrificed before modeling and on days 7， 14， 21， 28 and 42 after modeling for assessment of relevant indicators. To evaluate the therapeutic effect of drug intervention， the mice were given ECC-JHF Ⅱ and pirfenidone （PFD） by gavage starting on day 29 after modeling for 14 days of treatment， after which the mice were sacrificed. Pulmonary function， pathological changes， collagen deposition， lung tissue hardness and EMT markers were detected. Polyethylene glycol （PEG） composite hydrogels with different hardness were prepared in vitro using biomaterials such as eight-arm polyethylene glycol thiol （PEG-SH） and eight-arm polyethylene glycol maleimide （PEG-MAL）. Human type Ⅱ alveolar epithelial cells cultured in hard matrix culture dishes were treated with low， medium， and high doses of ECC-JHF Ⅱ （15.31， 30.63， 61.25 mg·L^-1） to observe the intervention effect of ECC-JHF Ⅱ on EMT induced by transforming growth factor beta 1 （TGF-β₁）. Human type Ⅱ alveolar epithelial cells cultured on soft （3.8 kPa） and hard （culture dishes， ~ GPa） matrices were treated with ECC-JHF Ⅱ， respectively. The mRNA and fluorescence expression levels of the epithelial marker E-cadherin （CDH1）， the mesenchymal marker N-cadherin （CDH2） and vimentin （VIM）， as well as ITG β₁， were detected by real-time quantitative polymerase chain reaction （Real-time PCR） and immunofluorescence. Western blot was used to detect the protein expression of CDH1， CDH2 and ITG β₁， and the biomechanical mechanism of ECC-JHF Ⅱ on EMT and pulmonary fibrosis was further verified by knocking down and specific activation of ITG β₁. ResultsECC-JHF Ⅱ treatment improved BLM-induced pulmonary fibrosis in mice， as evidenced by significantly increased minute ventilation （MV） and 50% expiratory flow at tidal volume （EF₅₀） （P<0.05）， and significantly increased tidal volume （TV） after treatment （P<0.01） compared with the model group. Immunohistopathological analysis revealed attenuated inflammation and alveolar injury， reduced deposition of type Ⅰ collagen （Col-Ⅰ）， and significantly decreased lung tissue stiffness （P<0.01）， thereby alleviating disease progression. The real-time PCR results showed that， compared with the model group， the ECC-JHF Ⅱ group showed increased CDH1 expression and decreased CDH2 and VIM expression in mouse lung tissues （P<0.05， P<0.01）， indicating that ECC-JHF Ⅱ inhibited the EMT process to ameliorate pulmonary fibrosis. In vitro experimental results showed that both ECC-JHF Ⅱ and matrix softening reversed the EMT phenotype switch. Specifically， compared with the hard matrix group， the cells cultured on the soft matrix exhibited significantly upregulated expression of the epithelial marker CDH1 （P<0.01） and significantly downregulated expression of the mesenchymal markers CDH2 and VIM （P<0.05）. Furthermore， ECC-JHF Ⅱ inhibited the expression of ITG β₁ both in vitro and in vivo. Knockdown and specific activation of ITG β₁ further confirmed that ITG β₁ is involved in the regulatory process by which ECC-JHF Ⅱ inhibits EMT and ameliorates pulmonary fibrosis. ConclusionECC-JHF Ⅱ and matrix softening can block the EMT process and ameliorate pulmonary fibrosis， and the underlying mechanism may be associated with the inhibition of ITG β₁-mediated mechanotransduction. This study reveals a novel mechanism of ECC-JHF Ⅱ intervention in pulmonary fibrosis from a biomechanical perspective.

Background/Aims: Non-pharmacological treatments are crucial for managing irritable bowel syndrome (IBS), yet patient engagement remains a challenge. Understanding patients' knowledge, attitudes, and practices regarding these treatments is essential for improving care. Methods: A cross-sectional study was conducted across 5 hospitals, from October 2023 to February 2024. A self-designed knowledge, attitudes, and practices questionnaire along with the IBS quality of life and IBS severity scoring system was administered, and 496 valid responses were analyzed. Statistical analyses included correlation tests, multivariate linear regression, and mediation effect analysis. Results: The median scores for knowledge, attitude, and practice were 28, 25.5, and 21, respectively. Significant positive correlations were found between knowledge-attitude (r = 0.195), knowledge-practice (r = 0.364), and attitude-practice (r = 0.151). The multivariate linear regression analysis further indicated that knowledge (β = 0.399, P < 0.001) and attitude (β = 0.219, P = 0.022) positively correlated with the practical performance. SEM revealed that knowledge had a significant direct effect on both attitude (β = 0.186, P = 0.013) and practice (β = 0.356, P = 0.006). However, the direct effect of attitude on practice was not significant, and attitude did not mediate the relationship between knowledge and practice. Conclusions IBS patients exhibit a significant gap between their positive attitudes and their actual practices concerning non-pharmacological treatments. Knowledge is a direct driver of practice, but positive attitudes alone are insufficient to translate into behavior. Healthcare providers must move beyond simply fostering positive attitudes and focus on targeted educational interventions that provide actionable knowledge and skills to improve patient outcomes.

AIM: To compare the differences in intraocular pressure and anterior segment biometric parameters among Tibetan populations permanent residing at different altitudes in Xizang autonomous region, and to explore the impact of high-altitude environments on ocular characteristics.

METHODS:This was a retrospective cross-sectional study. Data were collected from Tibetan patients who visited the People's Hospital of Xizang Autonomous Region from September 2019 to October 2021. Participants were divided into two groups based on their permanent residence altitude: a higher altitude group(2 500-3 750 m)and a very high-altitude group(>3 750 m). The eye with better best corrected visual acuity was selected for each participant. Intraocular pressure, refractive error, and anterior segment biometric measurements \〖white-to-white corneal diameter(WTW), central corneal thickness(CCT), anterior chamber depth(ACD), lens thickness(LT), axial length(AL)\〗 were recorded and compared between the two groups.

RESULTS: A total of 43 Tibetan patients(43 eyes)were enrolled in this study, comprising 23 males and 20 females, with a mean age of 57.88±13.90 y. There were 19 patients(19 eyes)in the very high-altitude group and 24 patients(24 eyes)in the higher altitude group. The mean intraocular pressure in the very high-altitude group was 11.79±1.72 mmHg, which was significantly lower than 13.44±2.43 mmHg in the higher altitude group(P=0.019). CCT in the very high-altitude group was 482.70±23.76 μm, significantly thinner than 503.00±31.09 μm in the higher altitude group(P=0.012). AL in the very high-altitude group was 22.96±0.96 mm, significantly shorter than 23.64±1.10 mm in the higher altitude group(P=0.020). No statistically significant differences were found between the two groups in WTW, ACD, LT, or refractive error(all P>0.05).

CONCLUSION:Among the Tibetan population in Xizang autonomous region, as the altitude of residence increases, intraocular pressure significantly decreases, CCT becomes thinner and AL shortens. These morphological changes suggest possible adaptive remodelling of the eye in very high-altitude environments, and a thinner cornea may be an important factor contributing to the lower measured intraocular pressure values.

Epilepsy is a chronic neurological disease characterized by abnormal synchronous discharges of brain neurons. The mutation of GRIN1， a key gene encoding the essential GluN1 subunit of N-methyl-D-aspartate （NMDA） receptors， is closely associated with the pathogenesis and progression of epilepsy. This review summarizes research advances in GRIN1 mutation-related epilepsy， with a focus on its molecular mechanisms， clinical phenotypes， factors influencing phenotypic heterogeneity， and treatment strategies. In terms of molecular mechanisms， GRIN1 mutations affect NMDA receptor function through gain-of-function and loss-of-function mechanisms. Clinical phenotypes show significant heterogeneity， including seizure types， age of onset， and comorbid neurodevelopmental disorders. This heterogeneity may be related to the domain where the mutation is located， the mutation type， and the degree of impact on receptor function. Regarding treatment， gain-of-function mutations can be managed with NMDA receptor antagonists， while loss-of-function mutations may be treated with positive allosteric modulators. The ketogenic diet has also demonstrated potential therapeutic effects. This review aims to provide references for basic research and clinical translation in GRIN1 mutation-related epilepsy， and to promote the development of precision diagnosis and treatment.

Objective:To conduct a systematic review of reported cases of autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by uromodulin ( UMOD) gene mutations (ADTKD- UMOD) in China, summarize the clinical, pathological and genetic variation characteristics, and analyze the genotype-phenotype correlation. Methods:It was a retrospective systematic analysis study. The search terms "UMOD", "ADTKD-UMOD", "uric acid kidney disease (UAKD)", "medullary cystic kidney disease type 2 (MCKD2)", and "familial juvenile hyperuricemic nephropathy type 1 (FJHN1)" were used, and relevant literature on ADTKD- UMOD cases in China were retrieved from PubMed, CNKI, Wanfang Data and Chinese Medical Journal Full-text Database. The data of the cases involved in the literature were collected and summarized, and the clinical and pathological characteristics and genetic variation features of Chinese ADTKD- UMOD patients were analyzed. The patients were divided into exon 3 mutation group and non-exon 3 mutation group based on the mutation sites, and the differences of clinical phenotypes between the two groups were compared. The patients were also divided into domain 8 cysteine (D8C) mutation group and non-D8C mutation group based on the mutation regions, and the differences of clinical phenotypes between the two groups were compared. Results:A total of 17 relevant articles on ADTKD- UMOD cases in China were retrieved, involving 57 patients from 34 families. The age at first diagnosis was 24.0 (20.0, 39.5) years. Fifty-three patients (93.0%) had a family history of nephropathy or hyperuricemia. Among the 48 patients with recorded blood uric acid levels, 36 patients (75.0%) had hyperuricemia, with age of 24.0 (20.3, 37.3) years. Fifty-four patients had chronic kidney disease assessment records, among which 46 patients (85.2%) developed chronic kidney disease, and 21 patients (38.9%) developed end-stage renal disease. The age of end-stage renal disease was 39.0 (24.0, 46.0) years, with age of 33.0 (21.0, 46.5) years in males and 39.5 (25.5, 45.5) years in females ( Z=-0.649, P=0.516). Twenty patients underwent renal biopsies, and 19/20 patients had tubular or interstitial lesions, and 9/20 patients had glomerular lesions, mainly manifested as focal segmental or global glomerulosclerosis. Forty patients had renal ultrasound examination records, among which 36 patients (90.0%) had abnormal results, with renal cysts being the most common type (12 patients, 30.0%). Among the 34 family cases, no ADTKD- UMOD hotspot mutation was found in the UMOD gene mutations. Thirty-two families (94.1%) were missense mutations, 26 families (76.5%) had mutation sites in exon 3, and 16 families (47.1%) had mutation regions in D8C. The proportion of hypertension in the non-exon 3 mutation group was higher than that in the exon 3 mutation group ( χ2=9.84, P=0.002). The proportion of males in the non-D8C mutation group was higher than that in the D8C mutation group ( χ2=4.97, P=0.026). Conclusions:The main clinical manifestations of Chinese ADTKD- UMOD patients are hyperuricemia, and the main renal histopathological changes are tubular and interstitial lesions. Some patients have glomerular lesions, which need to be differentiated from focal segmental glomerulosclerosis. Renal cysts detected by renal ultrasound can suggest the diagnosis of the disease. Missense mutation is the main type of UMOD gene mutations. The gene mutation region may be correlated with hypertension and gender.

Objective:To estimate the radiation dose to caregivers and the public from 177Lu- peptide receptor radionuclide therapy (PRRT) for pediatric neuroblastoma patients and determine the duration of contact restrictions, in order to provide a reference for relevant radiation protection measures. Methods:A retrospective study was conducted by collecting data from 18 pediatric neuroblastoma patients, aged between 3 and 13 (6.72±2.72), who received 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid-D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) treatment at the Nuclear Medicine Department of Shandong Cancer Hospital from June 2023 to July 2023. Absorbed dose rate in air at 0, 0.1, 0.5, 1 and 2 m from the patients was measured using a radiation-survey at 1, 4, 24, 48 and 96 h after administration. The whole-body region of interest was delined using HERMES software. Subsequently, curve regression fitting was performed using a biexponential function model. By incorporating hypothesized social contact durations, the effective doses received by family members and the public in contact with patients were estimated. Additionally, MIM software was used to outline the whole-body VOI to obtain the total volume of lesions, and the Pearson or Spearman correlation coefficient was employed to analyze the relationship between the absorbed dose rate in air and clinical indicators as well as the total volume of lesions. Results:The 177Lu-DOTATATE administration dose was (4 353.42±1 451.51) MBq. All patients were discharged from hospital 24 h after 177Lu-DOTATATE administration. At the time of discharge, patients had excreted (76.70±3.99)% of the administered activity, and the absorbed dose rate in air at 0.1, 1 and 2 m from the patients were (32.74±6.98), 3.68(3.01, 4.70) and (1.22±0.51) μSv/h, respectively. After being discharged, the radiation doses to caregivers from children aged 2-5 years and 5-13 years were (2.47±1.80) mSv and (0.88±0.47) mSv, respectively. The contact restriction duration was 2 d for nighttime sleeping with family members and 1 d for contact with other children. On the day of discharge, patients should limit their time on public transportation within 4 h and do not need to restrict private transportation. Conclusions:To ensure the effective dose kept within the safety limits stipulated by current regulations, it is necessary to implement contact restrictions for patients’ family members and the public. After implementing preventive measures, 177Lu-DOTATATE treatment is a safe radionuclide therapeutic option.

Objectives:This study aimed to explore the association between perceived mental stress (MS), lymphocyte subset variations, and coronary lesion severity in patients with coronary artery disease (CAD).Methods:Patients with CAD were enrolled in this study from September 2023 to May 2024. Perceived Stress Scale-14 (PSS-14) was used to evaluate MS during the last 1 month. Lymphocyte subsets were analyzed, including the percentage and absolute counts of CD3 +, CD3 +CD4 +, CD3 +CD8 +, CD3 -CD19 +, CD3 -CD56 +16 +, and the Th/Ts ratio. Statistical analysis was conducted using SPSS 24.0. Results:This study recruited patients with 323 CAD, with an average age of 61 (56, 68) years, including 203 males and 120 females. According to the PSS-14, a score of 14-42 and 43-70 were categorized as normal and increased MS, respectively. Patients with CAD with increased MS had significantly higher Gensini scores than those with normal MS [37(19,64) vs. 28(12,50), Z=-2.19, P=0.029]. Male CAD patients with increased MS exhibited significantly higher Gensini scores [39(20, 58) vs. 26(12, 45), Z=-2.37, P=0.018], levels of CD3 +CD8 +%[28.3%(23.6%,36.6%) vs. 25.9%(21.0%,32.4%), Z=-2.05, P=0.041], and CD3 +CD8 +absolute value [485 (346, 675) vs. 396 (309, 510) cells/μl, Z=-2.55, P=0.011] than those with normal MS. In male patients with CAD, a positive correlation was observed between Gensini scores (correlation coefficient: 0.181, P=0.011), PSS-14 scores, and CD3 +CD8 +absolute value (correlation coefficient: 0.162, P=0.038). Conclusion:This study reveals a positive correlation between MS and coronary stenosis severity, with notable sex differences. In male patients with CAD, higher levels of MS are associated with more severe coronary stenosis. The potential underlying mechanism may involve the regulation of lymphocyte subsets .