OBJECTIVE To investigate the cognition， attitudes， and current practices of Chinese physicians regarding biosimilars and their clinical switching， so as to provide a basis for the rational clinical application of biosimilars in China and the improvement of related policies.METHODS A national cross-sectional online questionnaire survey was conducted in 2025. Quota sampling was adopted， with quotas based on physicians’ sex， city tier， and specialty. Questionnaire invitations were distributed to licensed physicians， and physicians who had prescribed monoclonal antibody biosimilars were included for analysis. The questionnaire covered their familiarity with biosimilars， attitudes， clinical switching practices， and reasons. Data were processed using reliability and validity tests， dispersion analysis， and cross-tabulation analysis.RESULTS The questionnaire scale showed good reliability and validity， with Cronbach’s α coefficient ＞0.7 and KMO value ＞0.6. A total of 2 071 survey invitations were distributed， and 300 valid questionnaires were returned， with an effective response rate of 14.5%. Among the respondents， 75.3% had prescribed 3-5 types of monoclonal antibody biosimilars； only 35.3% were aware that China currently has no clear regulatory provisions on biosimilar switching； 46.3% and 47.3% of respondents believed that there was no difference in safety and efficacy， respectively， between biosimilars and originator products； 63.0% of respondents were concerned about the immunogenicity risk of long-term switching between originator drugs and biosimilars. A total of 92.3% of respondents had experience with biosimilar switching， 87.7% of which involved switching from originator products to biosimilars， and 28.2% of respondents had completed three or more switches in the same patient. Among the primary reasons for switching， non-medical factors accounted for 57.4%， higher than medical factors at 42.6%； “lower treatment cost after switching” was the most important reason for switching； 95.3% of respondents believed that informed consent should be obtained from patients before switching.CONCLUSIONS The surveyed physicians had basic knowledge of biosimilars， but their understanding of the relevant regulations of the national drug regulatory authority was insufficient. Although most physicians were concerned about the risks of non-medical switching， clinical switching was mostly driven by non-medical factors. It is recommended to strengthen policy education for medical professionals and standardize clinical switching behavior. The National Medical Products Administration should also promptly improve the interchangeability review standards and post-marketing surveillance system for biosimilars, so as to promote the rational use of biosimilars.

ObjectiveTo explore the mechanism of Huoxue Rongluo prescription （HXRLP） in repairing the blood-brain barrier （BBB） after ischemic stroke （IS）. MethodsMale C57BL/6 mice were randomly divided into sham operation （Sham） group， cerebral infarction model （MCAO） group， environmental circadian disruption with cerebral infarction model （ECD-MCAO） group， low-， medium-， and high-dose HXRLP （HXRLP-L， M， and H） groups （8.5， 17， 34 g·kg^-1·d^-1， respectively）， and positive drug butylphthalide （NBP） group （0.23 mL·d^-1）. In the Sham group， only the exposed blood vessels were isolated without suture insertion. In the other groups， the middle cerebral artery occlusion （MCAO） model of mice was prepared. In the ECD-MCAO group， HXRLP groups， and NBP group， the environmental circadian disruption （ECD） model was prepared. The mice in the Sham group， MCAO group， and ECD-MCAO group were given the same volume of soybean oil by gavage， while those in the other groups were given the corresponding drugs by gavage. Samples were collected after 7 consecutive days of administration. The mNSS score was used to evaluate the repair effect of HXRLP on neurological deficits after IS. Hematoxylin-eosin （HE） staining was used to assess the impact of HXRLP on the pathological damage of brain tissue after IS. 2，3，5-Triphenyltetrazolium chloride （TTC） staining and cerebral blood perfusion status were used to evaluate the repair effect of HXRLP on brain tissue damage after IS. Evans blue staining and transmission electron microscopy were used to evaluate the improvement effect of HXRLP on the permeability injury of BBB after IS. Immunofluorescence （IF） staining was used to observe the expression of von Willebrand Factor （vWF）， brain and muscle Arnt-like 1 （Bmal1）， and Occludin in brain tissue. Western blot was used to detect the protein expression of Bmal1， Occludin， tight junction protein （Claudin-5）， vascular endothelial growth factor （VEGF）， and angiopoietins（Ang）， and related analysis was conducted. ResultsCompared with the Sham group， the MCAO group exhibited significantly aggravated neurological deficits， cerebral infarction volume， brain pathological damage， and BBB leakage （P0.01） and significantly reduced cerebral blood perfusion （P0.01）. The expression of Bmal1， vWF， vascular endothelial growth factor A （VEGFA）， and Ang in brain tissue was significantly enhanced （P0.01）， while the expression of Occludin and Claudin-5 was significantly weakened （P0.01）. Compared with the MCAO group， the ECD-MCAO group showed significantly aggravated neurological deficits， cerebral infarction volume， and BBB leakage （P0.01）， obviously worsened brain pathological damage （P0.05）， significantly reduced cerebral blood perfusion （P0.01）， and significantly decreased expression of Bmal1， vWF， VEGFA， Ang， Occludin， and Claudin-5 in brain tissue （P0.01）. Compared with the ECD-MCAO group， the HXRLP groups of all doses presented significantly improved neurological deficits， cerebral infarction volume， brain pathological damage， and BBB leakage （P0.01）， significantly increased cerebral blood perfusion （P0.01）， and enhanced expression levels of Bmal1， vWF， VEGFA， Ang， Occludin， and Claudin-5 in brain tissue （P0.01）. ConclusionHXRLP can regulate the clock protein Bmal1 and promote the expression of VEGFA， Ang， Occludin， and Claudin-5， thereby improving BBB damage after IS.

Objective: To evaluate the safety and efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in the treatment of refractory autoimmune hemolytic anemia (AIHA). Methods: A retrospective analysis was performed on the clinical data of AIHA patients who underwent therapeutic whole blood exchange combined with lymphoplasmapheresis at our hospital from March 2022 to May 2025. Efficacy was assessed by comparing changes in hemoglobin, platelet count, and bilirubin levels before and after treatment. Safety was evaluated by analyzing vital signs before and after the procedure, parameters during the exchange, and adverse reactions. Results: A total of 12 AIHA patients were enrolled, completing 19 exchange procedures. The number of procedures per patient ranged from 1 to 3. The median treatment duration was 67 (65-73) minutes, with a median exchange volume of 2 025 (1 851-2 121) mL, comprising 4.5 (4-6) units of red blood cells and 1 350 (1 200-1 400) mL of plasma. Ten patients achieved partial remission, one achieved complete remission, and one showed no response, yielding an response rate of 91% (11/12). After a single session, hemoglobin increased significantly by 17.58±9.85 g/L (P<0.01), while platelets counts decreased by 45 (17.5, 79)×10 /L (P<0.05), and both systolic and diastolic blood pressure showed a significant elevation (P<0.05). However, no statistically significant differences were observed in total bilirubin, indirect bilirubin, white blood cell count, or heart rate. During the procedures, 4 adverse reactions occurred in 3 patients: one child experienced severe heart rate fluctuation twice consecutively, and two adults developed plasma allergies. All reactions resolved spontaneously without pharmacological intervention. Conclusion: The combination of therapeutic whole blood exchange and lymphoplasmapheresis appears to be a safe and effective treatment for refractory AIHA patients.

BACKGROUND:Traditional Chinese medicine has unique advantages in preventing and treating spleen-deficiency and hyperlipidemia.In basic studies,models of spleen-deficiency and hyperlipidemia are commonly found in rats,pigs,and other animals.This has limitations for medical research that can only use mouse models.It is urgent to establish and evaluate mouse models of spleen-deficiency and hyperlipidemia to support basic research on traditional Chinese medicine in preventing and treating spleen-deficiency and hyperlipidemia.OBJECTIVE:To establish a mouse model of spleen-deficiency hyperlipidemia.METHODS:Totally 24 C57BL/6J mice were randomly divided into normal group(n=12)and spleen-deficiency hyperlipemia group(n=12).Mice in normal group were fed basic diet.Mice in the spleen-deficiency hyperlipemia group were prepared with a diet disorder+fatigue internal injury+high-fat feeding method to establish a spleen-deficiency high-fat model.In the first 2 weeks,the mice were forced to swim to their endurance limit on a single day and were only fed cabbage,with free access to water.They were also gavaged with refined lard+high-fat feed on two-day intervals.After 2 weeks,the mice were fed a high-fat diet every day and the diet continued until 12 weeks.The mice were fed with a high-fat diet for 4 and 12 weeks,and their body weight,food intake,gripping strength,fecal water content,small intestinal charcoal propulsion rate,serum D-xylose and gastrin levels,spleen index and thymus index,blood lipid level,total body fat mass,body fat percentage,and liver lipid deposition were tested.RESULTS AND CONCLUSION:(1)Compared with the normal group,the body weight,fecal water content,total body fat mass,body fat percentage,triglyceride and total cholesterol levels of the mice in the spleen-deficiency hyperlipemia group fed with high-fat diet for 4 and 12 weeks were increased(P＜0.05);the daily food intake,gripping force,and D-xylose level of the mice fed with high-fat diet for 4 and 12 weeks were decreased(P＜0.05);the spleen index of the mice fed with high-fat diet for 4 weeks was increased(P＜0.05);the small intestinal carbon propulsion rate,gastrin level,spleen index,and thymus index of the mice fed with high-fat diet for 12 weeks were decreased(P＜0.05);the low-density lipoprotein cholesterol level of the mice fed with high-fat diet for 12 weeks was increased(P＜0.05).(2)The results of liver oil red O staining showed that the lipid deposition in the spleen-deficiency hyperlipemia group after 4 weeks of high-fat diet feeding was slightly more than that in the normal group,and the lipid deposition in the high-fat diet feeding for 12 weeks was significantly more than that in the normal group.(3)The results show that a stable spleen deficiency and hyperlipidemia mouse model can be prepared by the compound method of eating disorders,exhaustion,and high-fat feeding.

Objective:To analyze the relationship among thyroid autoimmunity (TAI), thyroid function, and gestational diabetes mellitus (GDM) in early pregnant women in Xi'an.Methods:A prospective study included pregnant women who underwent prenatal check-ups at the Northwest Women's and Children's Hospital from November 2020 to October 2021, with a gestational age of 6 to 14 weeks. Thyroid function, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and urinary iodine levels were measured, and the prevalence of thyroid disease and GDM was monitored. The subjects were divided into four groups: TPOAb positive only, TgAb positive only, both TPOAb and TgAb positive, and both TPOAb and TgAb negative, to compare the differences in the prevalence of thyroid disease and GDM among the groups. Statistical analysis was performed using Kruskal-Wallis rank-sum test, Bonferroni correction, Chi-square test, and a multivariate logistic regression model was used to analyze the relationship between TAI, thyroid disease, and GDM. Results:A total of 20 243 early pregnant women were included in this study, among which 1 615 (7.98%) were positive for TPOAb only; 865 (4.27%) were positive for TgAb only; 1 672 (8.26%) were positive for both TPOAb and TgAb (both positive group); and 16 091 (79.49%) were negative for both TPOAb and TgAb (both negative group). The thyroid stimulating hormone levels in the TPOAb positive only group, TgAb positive only group, and both positive group were significantly higher than those in the both negative group, respectively (Bonferroni correction, all P<0.05); the free thyroxine level in the TPOAb positive only group was significantly lower than that in the both negative group ( P<0.05). After adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing hypothyroidism during pregnancy was significantly increased in the both positive group ( OR=11.49, 95% CI: 2.84-46.39); the risk of developing subclinical hypothyroidism during pregnancy was significantly increased in the TgAb positive only group ( OR=1.99, 95% CI: 1.05-3.76) and the both positive group ( OR=3.74, 95% CI: 2.49-5.63); the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.43, 95% CI: 1.04-1.96) and the both positive group ( OR=1.94, 95% CI: 1.53-2.46). Among early pregnant women with normal thyroid function, after adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.46, 95% CI: 1.06-2.02) and the both positive group ( OR=1.80, 95% CI: 1.40-2.32). Conclusion:TgAb positive only is a risk factor for subclinical hypothyroidism and GDM. Screening for thyroid autoantibodies, especially TgAb, during pregnancy helps in the early identification of high-risk pregnant women for thyroid dysfunction and GDM.

Objective:To compare the clinical and laboratory characteristics and survival between Chinese and Western patients with myelodysplastic neoplasms (MDS) .Methods:Clinical and laboratory data were collected from 1,464 primary adult patients diagnosed with MDS at the Institute of Hematology & Blood Diseases Hospital from August 2016 to June 2024. Collected data were retrospectively analyzed and compared with 2,191 patients from the International Working Group for the Prognosis of Myelodysplastic Syndromes (IWG-PM) .Results:Chinese patients were significantly younger (median age: 56 years vs. 72 years, P<0.001) and experienced more severe hematopenia ( P<0.001) compared with patients from the IWG-PM. Further, Chinese patients exhibited a higher percentage of isolated del (20q), +8, and complex karyotypes as well as a lower percentage of normal karyotypes, del (5q), and -Y ( P<0.001). Higher U2AF1, NRAS, and NPM1 mutation rates and lower ASXL1, SF3B1, and RUNX1 mutation rates were observed in Chinese patients than in participants from the IWG-PM ( P<0.05). No significant difference in overall survival (OS) was found between the two groups (median OS: 48 [95% CI: 40 - 56]months, vs. 45[95% CI: 40 - 49] months; P=0.449). Among participants aged ≤45 years, Chinese patients demonstrated more trisomy 8 ( P=0.070) and U2AF1 mutation ( P<0.001) and higher 4-year OS rate compared with those from the IWG-PM (75.5% vs. 62.1%, P=0.001). Among participants aged ≥70 years, Chinese patients exhibited more complex karyotypes but fewer del (5q) as well as more NPM1 but less SF3B1 and TET2 compared with those from the IWG-PM ( P<0.05). Chinese patients demonstrated shorter survival (median OS: 20 [95% CI: 13 - 27] months vs. 37 [95% CI: 32 - 42] months, P<0.001) . Conclusion:Chinese and Western MDS patients differ in age of onset, clinical features, and cytogenetic or molecular genetic abnormalities, with significant differences persisting in age-matched groups. Although the OS is similar, disparities exist in survival for younger and older patients between the two populations.

Objective:To investigate the association between pre- and post-treatment gene mutation profiles and clinical outcomes (treatment response and prognosis) in patients with myelodysplastic syndromes with excess blasts (MDS-EB) receiving hypomethylating agent (HMA) monotherapy.Methods:The clinical characteristics, treatment efficacy, and survival outcomes of 69 treatment-naive patients with MDS-EB who underwent next-generation sequencing (NGS) before treatment and completed at least 4 cycles of HMA monotherapy at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC, between June 2016 and September 2023, were retrospectively analyzed.Results:① The cohort comprised 47 males and 22 females with a median age of 62 years (range: 41-80). Thirty-nine patients were classified as MDS-EB1 and 30 as MDS-EB2. The median number of treatment cycles was 6 (range: 4-35). The median follow-up duration was 22 months (range: 5-72), and the median overall survival (OS) was 32 months (95% CI: 27-43). ② The presence of DTA (DNMT3A, TET2, or ASXL1) mutations, signaling pathway mutations, transcription factor mutations, or splicing factor mutations before HMA treatment showed no significant association with the best response within 4 treatment cycles, duration of response (DOR), or OS. TP53 mutation status was significantly associated with DOR and shorter OS. The median DOR was 3 months (95% CI: 1-10) for patients with biallelic TP53 mutations, 10 months (95% CI: 3-34) for those with monoallelic TP53 mutations, and 16 months (95% CI: 8-27) in patients without TP53 mutations ( P=0.032). The median OS was 16 months (95% CI: 7-38), 15 months (95% CI: 6-40), and 35 months (95% CI: 14-91), respectively ( P<0.001). ③ Neither the Revised International Prognostic Scoring System (IPSS-R) nor the Molecular International Prognostic Scoring System (IPSS-M) could predict the best response within 4 treatment cycles or DOR in patients receiving HMA therapy. ④ Among patients without TP53 mutations, the median OS was 55 months (95% CI: 9-106) for the major clone significant clearance group ( n=14) and 31 months (95% CI: 16-184) for the major clone non-significant clearance group ( n=10) ( P=0.013). For patients who responded to HMA treatment and had significant major clone clearance, the 3-year OS rate reached (77.8±13.9) %. Conclusion:For MDS-EB patients receiving HMA monotherapy, single gene mutations, IPSS-R, and IPSS-M could not effectively predict treatment outcomes before therapy. However, for patients without TP53 mutations, monitoring the degree of major clone clearance by NGS during treatment may predict the long-term efficacy in MDS patients receiving HMA therapy.

Objective:To analyze the clinical characteristics, therapeutic responses, and survival outcomes of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) .Methods:We retrospectively reviewed clinical data from 16 consecutive patients diagnosed with L-HES at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, between July 2019 and October 2024. A control group of 65 patients with idiopathic hypereosinophilic syndrome (iHES), diagnosed during the same period, was used for comparison. Clinical and laboratory characteristics, therapeutic responses, and survival outcomes were compared between the two groups.Results:The most frequently involved organs at presentation in patients with L-HES were the skin (75.0%), gastrointestinal tract (25.0%), respiratory tract (18.8%), lymph nodes (18.8%), heart (12.5%), and spleen (6.3%). Compared with iHES patients, patients with L-HES had a significantly higher incidence of skin involvement ( P=0.016), with no statistically significant differences observed in the involvement of other organs. No statistically significant differences were found in complete blood count parameters between the two groups. Multiparameter flow cytometry revealed that the median percentage of CD3 -CD4 + T cells in the peripheral blood of patients with L-HES was 4.08% ( IQR: 1.64%-32.78%), with a median absolute count of 0.10 (0.05-0.55) ×10 9/L. Serum immunoglobulin E (IgE) levels were significantly higher in the L-HES group than in the iHES group ( P<0.001). Clonal rearrangement of T-cell receptor genes was detected in 75.0% of patients with L-HES. After diagnosis, 14 patients with L-HES received glucocorticoids as first-line therapy, yielding an overall response rate of 92.9%. During glucocorticoid tapering, 11 patients experienced recurrent eosinophilia or worsening of clinical symptoms. Three patients received interferon-alpha as a second-line therapy, with two achieving complete remission. After a median follow-up of 16 months ( IQR: 8-28 months), one patient died of cardiac insufficiency 8 months after diagnosis, and no cases of lymphoma transformation were observed. The 2-year overall survival rate was (91.7±8.0) %, which did not significantly differ from that of the iHES group (96.2±2.6) % ( P=0.746) . Conclusions:Patients with L-HES generally have a favorable prognosis and are often characterized by skin involvement and significantly elevated serum IgE levels at diagnosis. They typically respond well to glucocorticoid therapy, although relapse is common during dose tapering. Interferon-alpha may serve as an effective second-line therapeutic option.

Objective:To identify the prognostic value of the Revised 15-item Myelodysplastic Syndrome-specific frailty scale (FS-15) in Chinese patients with myelodysplastic syndromes (MDS) .Methods:This retrospective study analyzed 812 patients with newly diagnosed MDS admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from August 2016 to June 2023. Patients were assessed using the FS-15 and subsequently categorized into frail and non-frail groups. Clinical and laboratory characteristics, as well as overall survival (OS), were compared between these groups.Results:① The median patient age was 55 years ( IQR 45–64), with a median follow-up of 22.5 months (95% CI: 20.2–24.9) and a median OS of 43.3 months (95% CI: 36.8–49.8). The median FS-15 score was 0.42, with a cutoff value of 0.44. Male patients demonstrated higher median FS-15 scores than female patients (0.42 vs 0.38, P=0.006). In both the Revised International Prognostic Scoring System (IPSS-R; P=0.001) and Molecular International Prognostic Scoring System (IPSS-M; P=0.014) stratifications, FS-15 scores were significantly higher in the very high-risk group compared with the very low-risk group. ② The median OS was 54.7 months (95% CI: 47.5–NA) and 31.5 months (95% CI: 22.9–41.0) in the nonfrail ( n=452) and frail groups ( n=360), respectively ( P<0.001). The 3-year OS rates were (63.2 ± 3.2) % and (46.4 ± 3.6) % for the non-frail and frail groups, with 5-year OS rates of (49.9 ± 4.7) % and (32.0 ± 4.3) %, respectively ( P<0.001). ③Subgroup analysis revealed that nonfrail patients demonstrated significantly higher 3-year OS rates than frail patients in both the IPSS-M low-risk and very high-risk groups (all P<0.05). Similarly, nonfrail patients demonstrated superior 3-year OS rates compared with frail patients in the IPSS-R very low-risk, low-risk, and high-risk groups (all P<0.05). ④Among patients receiving hypomethylating agent therapy, the overall response rate was significantly higher in the non-frail group than in the frail group (86.7% vs 64.6%, P=0.007). Moreover, the frail group experienced higher rates of treatment-related adverse events, including febrile neutropenia (67.1% vs 47.4%, P=0.016) and liver function abnormalities (30.0% vs 14.5%, P=0.023), compared with the non-frail group. Conclusion:The FS-15 frailty score is a feasible and effective tool for assessing frailty in patients newly diagnosed with MDS in China and serves as a valuable prognostic indicator.