Objective:To investigate the infection rate of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with severe aplastic anemia (SAA) after intensive immunosuppressive therapy in combination with a thrombopoietin receptor agonist (lST+TPO-RA) as well as assess the clinical impact of treatment.Methods:A retrospective, case series study was undertaken involving patients with SAA who were admitted to Soochow Hopes Hematonosis Hospital, The First Affiliated Hospital of Soochow University, and Zhengzhou Third People′s Hospital from June 2022 to February 2025. Thirty patients with complete CMV and EBV monitoring data after IST+TPO-RA treatment were enrolled. The first activation time of CMV and EBV, the maximum viral load, the first negative conversion time, and blood routine tests within 3 days before CMV and EBV positivity, during the positive period, and within 3 days after turning negative were recorded. The patients were followed up for 9 months after the completion of IST. One-way analysis of variance was used to compare the changes of blood routine before and after virus positivity and after turning negative. The χ2 test was used to compare the viral infection rate and the therapeutic effect of IST between the two groups. Results:The 30 SAA patients comprised 15 males and 15 females with an average age of (40.0±16.9) years. Of the 30 patients, 18 (60.0%) were infected with CMV and 6 (20.0%) with EBV. Among them, 17 cases received rabbit anti-human thymocyte immunoglobulin (r-ATG) treatment (r-ATG group), 13 cases received porcine anti-human lymphocyte immunoglobulin (p-ALG) treatment (p-ALG group). The CMV infection rate was significantly higher in the r-ATG group than in the p-ALG group (15/17 vs. 3/13, χ2=13.03, P<0.001); meanwhile, the rate of EBV infection was only slightly higher in the r-ATG group than in the p-ALG group, and the difference did not reach statistical significance (5/17 vs. 1/13, χ2=2.17, P=0.196). In patients infected with CMV, neutrophil, hemoglobin, and platelet counts were significantly decreased during the infection phase, followed by significant increases after CMV clearance ( F=14.48, 11.38, 4.73; all P<0.05). No significant differences in treatment efficacy were found between the r-ATG and p-ALG groups at 3, 6, and 9 months post-IST (all P>0.05). Conclusions:This preliminary study showed that the incidence of CMV and EBV infection in patients with SAA increased after IST, with CMV infections occurring significantly more frequently than EBV infections. The CMV infection rate was significantly higher in patients treated with r-ATG than in those receiving p-ALG. CMV infection was associated with notable alterations in hematological parameters, highlighting the need for close clinical monitoring.

Age-related macular degeneration(AMD)is one of the leading causes of blindness in the elderly.Wet AMD(nAMD)accounts for more than 90％of AMD-related vision loss.Pathologically,nAMD is defined by choroidal neovascu-larization(CNV)and chronic retinal inflammation driven by oxidative stress,complement activation,pro-inflammatory cy-tokines,and overexpression of vascular endothelial growth factor(VEGF).Yet anti-VEGF monotherapy often falls short.The nuclear factor kappa-B(NF-κB)signaling cascade,acting through both canonical and non-canonical pathways,or-chestrates the expression of genes governing immunity,inflammation,apoptosis,and angiogenesis.In nAMD,oxidative stress and complement fragments ignite NF-κB,unleashing a repertoire of pro-inflammatory and pro-angiogenic mediators that fuel CNV.Pharmacologic or genetic suppression of NF-κB dampens both inflammation and neovascularization,attenua-ting experimental CNV.Thus,dissecting the molecular machinery of NF-κB signaling in nAMD may uncover novel combina-tion strategies that enhance therapeutic efficacy and curb anti-VEGF resistance.

Age-related macular degeneration(AMD)is one of the leading causes of blindness in the elderly.Wet AMD(nAMD)accounts for more than 90％of AMD-related vision loss.Pathologically,nAMD is defined by choroidal neovascu-larization(CNV)and chronic retinal inflammation driven by oxidative stress,complement activation,pro-inflammatory cy-tokines,and overexpression of vascular endothelial growth factor(VEGF).Yet anti-VEGF monotherapy often falls short.The nuclear factor kappa-B(NF-κB)signaling cascade,acting through both canonical and non-canonical pathways,or-chestrates the expression of genes governing immunity,inflammation,apoptosis,and angiogenesis.In nAMD,oxidative stress and complement fragments ignite NF-κB,unleashing a repertoire of pro-inflammatory and pro-angiogenic mediators that fuel CNV.Pharmacologic or genetic suppression of NF-κB dampens both inflammation and neovascularization,attenua-ting experimental CNV.Thus,dissecting the molecular machinery of NF-κB signaling in nAMD may uncover novel combina-tion strategies that enhance therapeutic efficacy and curb anti-VEGF resistance.

Objective:To investigate the infection rate of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with severe aplastic anemia (SAA) after intensive immunosuppressive therapy in combination with a thrombopoietin receptor agonist (lST+TPO-RA) as well as assess the clinical impact of treatment.Methods:A retrospective, case series study was undertaken involving patients with SAA who were admitted to Soochow Hopes Hematonosis Hospital, The First Affiliated Hospital of Soochow University, and Zhengzhou Third People′s Hospital from June 2022 to February 2025. Thirty patients with complete CMV and EBV monitoring data after IST+TPO-RA treatment were enrolled. The first activation time of CMV and EBV, the maximum viral load, the first negative conversion time, and blood routine tests within 3 days before CMV and EBV positivity, during the positive period, and within 3 days after turning negative were recorded. The patients were followed up for 9 months after the completion of IST. One-way analysis of variance was used to compare the changes of blood routine before and after virus positivity and after turning negative. The χ2 test was used to compare the viral infection rate and the therapeutic effect of IST between the two groups. Results:The 30 SAA patients comprised 15 males and 15 females with an average age of (40.0±16.9) years. Of the 30 patients, 18 (60.0%) were infected with CMV and 6 (20.0%) with EBV. Among them, 17 cases received rabbit anti-human thymocyte immunoglobulin (r-ATG) treatment (r-ATG group), 13 cases received porcine anti-human lymphocyte immunoglobulin (p-ALG) treatment (p-ALG group). The CMV infection rate was significantly higher in the r-ATG group than in the p-ALG group (15/17 vs. 3/13, χ2=13.03, P<0.001); meanwhile, the rate of EBV infection was only slightly higher in the r-ATG group than in the p-ALG group, and the difference did not reach statistical significance (5/17 vs. 1/13, χ2=2.17, P=0.196). In patients infected with CMV, neutrophil, hemoglobin, and platelet counts were significantly decreased during the infection phase, followed by significant increases after CMV clearance ( F=14.48, 11.38, 4.73; all P<0.05). No significant differences in treatment efficacy were found between the r-ATG and p-ALG groups at 3, 6, and 9 months post-IST (all P>0.05). Conclusions:This preliminary study showed that the incidence of CMV and EBV infection in patients with SAA increased after IST, with CMV infections occurring significantly more frequently than EBV infections. The CMV infection rate was significantly higher in patients treated with r-ATG than in those receiving p-ALG. CMV infection was associated with notable alterations in hematological parameters, highlighting the need for close clinical monitoring.

Objective:This study aimed to compare the efficacy and safety between high-dose intravenous iron and oral iron in treating iron deficiency anemia (IDA) .Methods:This prospective randomized controlled study (1∶1) enrolled 338 patients with IDA at The First Affiliated Hospital of Soochow University, Suzhou Hongci Hematology Hospital, and Huai’an Second People’s Hospital from June 1, 2022, to January 19, 2024. Of all the patients, 169 received high-dose intravenous iron therapy and 169 received oral iron treatment for 12 weeks of observation. Focus on the hemoglobin (HGB) change from baseline to week 4, secondary focus was on the HGB and iron metabolism parameters (serum iron [SI], transferrin saturation [TSAT], total iron binding force [TIBC], serum ferritin [SF]), and changes in the fatigue score, efficacy, and treatment-related adverse effects were monitored throughout in the two treatment groups.Results:The HGB levels were improved in both treatments, but the HGB improved faster in the intravenous group compared with the oral group. HGB increased from (76.8±15.0) g/L to (118.0±13.3) g/L in the intravenous group and from (77.9±11.6) g/L to (104.3±15.0) g/L in the oral group after 4 weeks of treatment. The increase from baseline in the intravenous group (40.7±17.3) g/L was significantly higher than that in the oral group (27.2±17.5) g/L ( P<0.001). The intravenous group demonstrated a more significant early effect than the oral group in terms of iron metabolism parameter improvement. SI, TSAT, TBIC, and SF increased better from baseline at 4 weeks in the intravenous group than in the oral group ( P<0.001). Additionally, the intravenous group exhibited better fatigue scores for early improvement than the oral group ( P<0.001). The incidence of total adverse effects was similar in the intravenous group as compared to the oral group (3.5% [6/169] vs 5.9% [10/169], P=0.442) . Conclusion:High doses of intravenous iron quickly boost HGB early, causing rapid improvement in SI, TSAT, TBIC, SF, and patient fatigue scores. The patient was well tolerated.

Objective:This study aimed to compare the efficacy and safety between high-dose intravenous iron and oral iron in treating iron deficiency anemia (IDA) .Methods:This prospective randomized controlled study (1∶1) enrolled 338 patients with IDA at The First Affiliated Hospital of Soochow University, Suzhou Hongci Hematology Hospital, and Huai’an Second People’s Hospital from June 1, 2022, to January 19, 2024. Of all the patients, 169 received high-dose intravenous iron therapy and 169 received oral iron treatment for 12 weeks of observation. Focus on the hemoglobin (HGB) change from baseline to week 4, secondary focus was on the HGB and iron metabolism parameters (serum iron [SI], transferrin saturation [TSAT], total iron binding force [TIBC], serum ferritin [SF]), and changes in the fatigue score, efficacy, and treatment-related adverse effects were monitored throughout in the two treatment groups.Results:The HGB levels were improved in both treatments, but the HGB improved faster in the intravenous group compared with the oral group. HGB increased from (76.8±15.0) g/L to (118.0±13.3) g/L in the intravenous group and from (77.9±11.6) g/L to (104.3±15.0) g/L in the oral group after 4 weeks of treatment. The increase from baseline in the intravenous group (40.7±17.3) g/L was significantly higher than that in the oral group (27.2±17.5) g/L ( P<0.001). The intravenous group demonstrated a more significant early effect than the oral group in terms of iron metabolism parameter improvement. SI, TSAT, TBIC, and SF increased better from baseline at 4 weeks in the intravenous group than in the oral group ( P<0.001). Additionally, the intravenous group exhibited better fatigue scores for early improvement than the oral group ( P<0.001). The incidence of total adverse effects was similar in the intravenous group as compared to the oral group (3.5% [6/169] vs 5.9% [10/169], P=0.442) . Conclusion:High doses of intravenous iron quickly boost HGB early, causing rapid improvement in SI, TSAT, TBIC, SF, and patient fatigue scores. The patient was well tolerated.

With the boom of China's innovative pharmaceutical industry, licensing-in model has gradually become an important research and development model for innovative pharmaceutical companies. The in-licensed drugs at different stages need different research and development (R&D) strategy in China. The pharmaceutical companies take the responsibility to comprehensively collate the oversea clinical data and conduct a detailed analysis of clinical pharmacology, safety, efficacy and ethnic sensitivity. Clinical R&D strategy should be made based on the results of the above data and analysis. We encourage high-quality drugs which fill unmet clinical needs licensed in, and as early as possible, so as to conduct multi-regional clinical trials (MRCTs). The clinical R&D strategy in China is particularly important for the drug's approval. Guidelines published by the National Medical Products Administration (NMPA) and clinical associations should be followed. Communications about clinical R&D strategy with Center of Drug Evaluation (CDE) are encouraged.
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Antineoplastic Agents/therapeutic use* ; China ; Drug Industry ; Humans ; Lung Neoplasms/drug therapy* ; Pharmaceutical Preparations

The rapid changes in the research and development environment of new anti-tumor drugs in China have brought various challenges to drug innovation. How to explore the clinical advantages of new drugs in the early phase, and design scientific, reasonable and efficient pivotal clinical trials for drug registration accordingly, is one of the key challenges. This article takes innovative new drugs for hematological malignancies as an example, comprehensively elaborates the considerations on the timing for entering the pivotal clinical trial and the key elements of the trial design from the perspective of clinical reviewers.

Hemophilia is the only rare hereditary hemorrhagic disorder included in the First Rare Diseases catalogue. However, rare bleeding diseases identified in the clinic are far more common than hemophilia. Most other rare hemorrhagic disorders have less effective treatment than hemophilia. Hemophilia has a history of successful drug development in rare hemorrhagic diseases, and the cycle between clinical research and drug development has been gradually realized. Drug research and pharmaceutical companies can refer to the drug research and development process in the field of hemophilia, learn from the experience of hemophilia drug research and develop treatments. The industry can increase drug development by strengthening basic research, focusing on the value of natural history research, the application of quantitative pharmacological tools and improving the efficiency of drug development to meet the urgent unmet medical needs of patients with rare hemorrhagic diseases.

Objective To investigate the effects of shoes type (barefoot, ordinary running shoes, minimalist shoes) and walking speed (jogging, walking at normal speed) on biomechanical parameters of knee joint, so as to provide theoretical reference for scientific fitness. Methods Vicon three-dimensional （3D） motion capture system and Kistler 3D force plate were used to collect biomechanical parameters of lower limbs from 10 subjects during walking at different speed with different shoes. Two-way (2 walking conditions × 3 shoe conditions) repeated measures analysis of variance was used to statistically analyze each dependent variable. Results Compared with jogging, the lateral excursion of plantar center of pressure (COP) was greater, the moment arm in frontal plane, the adduction moment and peak loading rate of knee joint were smaller, but the angular impulse of knee joint in frontal plane was greater. Compared with ordinary running shoes, the stride length was decreased, the lateral excursion of COP was greater, and the moment arm of knee joint in frontal plane, the knee adduction moment, the peak load rate and the angular impulse of knee joint in frontal plane were smaller. Conclusions In order to reduce the angular impulse and peak loading rate of knee joint in frontal plane, it is recommended to jog with small strides for ordinary people with minimalist footwear.