Clinical Benefit, Price, and Regulatory Approval of Cancer Drugs Granted Breakthrough Therapy Designation in China, 2020-2024.

Importance: The China National Drug Administration (NMPA) established the breakthrough therapy designation (BTD) in 2020 to encourage the accelerated development of drugs for the prevention and treatment of diseases that are life-threatening. However, the differences between BTD and non-BTD cancer drugs regarding clinical benefit, regulatory approval, and price are unclear. Objectives: To compare BTD and non-BTD cancer drugs in clinical benefit (defined as efficacy and safety), novelty, time to approval, and average monthly treatment price. Design, Setting, and Participants: This cross-sectional study analyzes the original indication of BTD and non-BTD novel cancer drugs approved by the NMPA between July 8, 2020, and July 8, 2024. Data on efficacy, safety, regulatory approval, and price of cancer drugs were extracted from pivotal clinical trials based on review reports published by the NMPA, peer-reviewed articles or meeting reports, and winning bid prices for cancer drugs in the Chinese provincial-level centralized procurement process. Main Outcomes and Measures: The main outcome was the efficacy and safety associated with BTD vs non-BTD cancer drugs, including progression-free survival (PFS), response rate (RR), duration of response, serious adverse events, grade 3 or higher adverse events, and treatment-related deaths. In addition, the time to approval, novelty, and initial and latest average monthly treatment prices were evaluated, as well as the average annual reduction rate (AARR; the sum of the reduction rates divided by the number of years for the monthly treatment price) for these cancer drugs. Results: Between July 2020 and July 2024, 18 BTD (36%) and 32 non-BTD (64%) cancer drugs were approved by the NMPA. The median (IQR) clinical development time for BTD drugs was significantly shorter than for non-BTD drugs (5.6 [95% CI, 4.3-7.3] vs 6.6 [95% CI, 6.0-8.5] years; P = .02). No significant differences were observed in PFS (HR, 0.44 [95% CI, 0.38-0.52] vs HR, 0.51 [95% CI, 0.40-0.65]; P = .20), PFS gained (median [IQR], 5.4 [3.9-7.0] vs 2.7 [2.6-5.9] months; P = .77), RR (58% [95% CI, 45%-74%] vs 59% [95% CI, 51%-69%]; P = .85), and duration of response (median [IQR], 18.0 [15.0-21.6] vs 11.1 [7.4-17.4] months; P = .09) between BTD and non-BTD drugs. The rates of serious adverse events (37% [95% CI, 26%-52%] vs 32% [95% CI, 27%-36%]; P = .45), adverse events grade 3 or higher (64% [95% CI, 53%-77%] vs 55% [95% CI, 45%-68%]; P = .31), and treatment-related deaths (2% [95% CI, 1%-4%] vs 1% [95% CI, 1%-2%]; P = .10) were similar between BTD and non-BTD drugs. BTD drugs are more likely to be first-in-class drugs (5 of 18 [28%] vs 1 of 32 [3%]; P = .02). Differences in the median (IQR) initial ($5665 [$3542-$9321] vs $3361 [$2604-$5474]; P = .06) and latest ($5665 [$1553-$9321] vs $2145 [$1318-$4276]; P = .18) average monthly treatment prices for BTD drugs and non-BTD drugs were not significant. The median (IQR) AARRs for BTD drugs and non-BTD drugs were 15.2% (0%-46.9%) and 19.8% (1.0%-42.9%), respectively. Conclusions and Relevance: The findings of this cross-sectional study suggest that BTD has facilitated faster time to market for cancer drugs and improved novelty, but the price of treatment is relatively higher. There was no significant difference on comparative efficacy and safety.

Mapping the cell therapy landscape: insights into clinical trials and regulatory advances in China.

In recent years, cell therapy research and commercialization have significantly accelerated, especially after the US FDA approved CAR-T therapy. While cell therapy now leads immuno-oncology in clinical trials, challenges such as redundant R&D, target clustering, and unmet clinical need remain. Since 2017, China has established a dual-track regulatory framework, facilitating rapid growth in its cell therapy pipeline, making it the second largest in the world. Despite this progress, China faces similar global challenges. Our study covers 2,794 registered cell therapy clinical trials in China, including 2,045 for immune cell, 683 for stem cell, and 66 for other somatic cell. It compares cell therapy products approved in China, the US, EU, and Japan, analyzes the evolving clinical trials landscape, and highlights the characteristics of investigator-initiated trials (IITs) and industry-sponsored trials (ISTs) in China. Our findings indicate that despite the high disease burden and unmet clinical needs for solid tumors in China, over 38% of trials between 2021 and 2023 focused on hematologic malignancies with established targets like CD19 and BCMA. Over 90% of trials are IITs, which show notable clinical differences from ISTs. We recommend that Chinese regulators establish specific guidelines to promote clinical-value-driven research. Stricter regulatory standards should also be implemented to minimize redundant R&D. Additionally, a value-based reimbursement system for within-class targeted cell therapy products may further reduce duplicated R&D efforts. Given the prevalence of IITs, specifying requirements for IITs could create a new pathway to accelerate product development and better address unmet clinical needs in China.

Exploration on cold adaptation of Antarctic lichen via detection of positive selection genes.

Lichen as mutualistic symbiosis is the dominant organism in various extreme terrestrial environment on Earth, however, the mechanisms of their adaptation to extreme habitats have not been fully elucidated. In this study, we chose the Antarctic dominant lichen species Usnea aurantiacoatra to generate a high-quality genome, carried out phylogenetic analysis using maximum likelihood and identify genes under positive selection. We performed functional enrichment analysis on the positively selected genes (PSGs) and found that most of the PSGs focused on transmembrane transporter activity and vacuole components. This suggest that the genes related to energy storage and transport in Antarctic U. aurantiacoatra were affected by environmental pressure. Inside of the 86 PSGs screened, two protein interaction networks were identified, which were RNA helicase related proteins and regulator of G-protein signaling related proteins. The regulator of the G-protein signaling gene (UaRGS1) was chosen to perform further verification by the lichen genetic manipulation system Umbilicaria muhlenbergii. Given that the absence of UmRgs1 resulted in elevated lethality to cold shock, the role for UaRgs1 in Antarctic U. aurantiacoatra resistance to cold can be inferred. The investigation of lichen adaptation to extreme environments at the molecular level will be opened up.

Role of arterial blood glucose and interstitial fluid glucose difference in evaluating microcirculation and clinical prognosis of patients with septic shock: a prospective observational study.

BACKGROUND: Microcirculation abnormality in septic shock is closely associated with organ dysfunction and mortality rate. It was hypothesized that the arterial blood glucose and interstitial fluid (ISF) glucose difference (GA-I) as a marker for assessing the microcirculation status can effectively evaluate the severity of microcirculation disturbance in patients with septic shock. METHODS: The present observational study enrolled patients with septic shock admitted to and treated in the intensive care unit (ICU) of a tertiary teaching hospital. The parameters reflecting organ and tissue perfusion, including lactic acid (Lac), skin mottling score, capillary refill time (CRT), venous-to-arterial carbon dioxide difference (Pv-aCO2), urine volume, central venous oxygen saturation (ScvO2) and GA-I of each enrolled patient were recorded at the time of enrollment (H0), H2, H4, H6, and H8. With ICU mortality as the primary outcome measure, the ICU mortality rate at any GA-I interval was analyzed. RESULTS: A total of 43 septic shock patients were included, with median sequential organ failure assessment (SOFA) scores of 10.5 (6-16), and median Acute Physiology and Chronic Health Evaluation (APACHAE) II scores of 25.7 (9-40), of whom 18 died during ICU stay. The GA-I levels were negative correlation with CRT (r = 0.369, P < 0.001), Lac (r = -0.269, P < 0.001), skin mottling score (r=-0.223, P < 0.001), and were positively associated with urine volume (r = 0.135, P < 0.05). The ICU mortality rate of patients with septic shock presenting GA-I ≤ 0.30 mmol/L and ≥ 2.14 mmol/L was significantly higher than that of patients with GA-I at 0.30-2.14 mmol/L [65.2% vs. 15.0%, odds ratio (OR) = 10.625, 95% confidence interval (CI): 2.355-47.503]. CONCLUSION: GA-I was correlated with microcirculation parameters, and with differences in survival. Future studies are needed to further explore the potential impact of GA-I on microcirculation and clinical prognosis of septic shock, and the bedside monitoring of GA-I may be beneficial for clinicians to identify high-risk patients.

Phase 3 study of gilteritinib versus salvage chemotherapy in predominantly Asian patients with relapsed/refractory FLT3-mutated acute myeloid leukemia.

The phase 3 COMMODORE trial evaluated gilteritinib versus salvage chemotherapy (SC) in a predominantly Asian relapsed/refractory (R/R) FLT3-mutated (FLT3mut+) acute myeloid leukemia (AML) patient population. The primary endpoint was overall survival (OS); secondary endpoints included event-free survival (EFS) and complete remission (CR) rate. As of June 30, 2020 (interim analysis: 32.2 months after study initiation), 234 patients were randomized (gilteritinib, n = 116; SC, n = 118). Median OS was significantly longer with gilteritinib versus SC (9.6 vs. 5.0 months; HR 0.566 [95% CI: 0.392, 0.818]; p = 0.00211) with a median follow-up of 10.3 months. Median EFS was also significantly longer with gilteritinib (2.8 vs. 0.6 months; HR 0.551 [95% CI: 0.395, 0.769]; p = 0.00004). CR rates with gilteritinib and SC were 16.4% and 10.2%, respectively; composite CR rates were 50.0% and 20.3%, respectively. Exposure-adjusted grade ≥3 adverse event (AE) rates were lower with gilteritinib (58.38 events/patient-year [E/PY]) versus SC (168.30 E/PY). Common AEs with gilteritinib were anemia (77.9%) and thrombocytopenia (45.1%). Gilteritinib plasma concentration peaked ~4 h postdose; ~3-fold accumulation occurred with multiple dosing. The COMMODORE trial demonstrated that gilteritinib significantly improved OS and EFS in predominantly Asian patients, validating the outcomes of gilteritinib from the ADMIRAL trial in R/R FLT3mut+ AML.

A Modeling Study Recurrent Tuberculosis Towards End TB Strategy - China, 2025-2035.

What is already known about this topic?: The recurrence of tuberculosis (TB) following successful treatment presents a significant challenge. What is added by this report?: Achieving the global End TB Strategy milestones and targets with the current strategies in China is challenging. However, interventions following recovery to prevent recurrence, in conjunction with preventive treatment for latent TB infection (LTBI), will aid in meeting these objectives. What are the implications for public health practice?: Implementing interventions to mitigate recurrence is essential for improving TB control strategies both in China and worldwide. Concurrently, the development of new drugs and vaccines should focus on preventing TB recurrence.

Case report: a rare case of intradural and pleural wall cystic echinococcosis.

BACKGROUND: Cystic echinococcosis (CE) is prevalent in livestock farming regions around the world. However, it remains relatively rare compared to other infectious diseases. CE typically affects the liver, lungs, brain, and kidneys. Spinal and pleural wall involvement is exceedingly rare. We report a unique case of intradural and pleural wall CE in a young male, successfully treated with surgery and postoperative medication. CASE PRESENTATION: A 19-year-old Tibetan male from the Qinghai-Tibet Plateau was diagnosed with intradural and pleural wall CE through imaging, serology, and surgical pathology. According to the Dew/Braithwaite & Lees (BL) classification, his condition was an exceptionally rare form of spinal echinococcosis, compounded by an even rarer pleural wall involvement. Prompt surgical intervention and postoperative medication resulted in significant improvement in spinal cord compression symptoms. CONCLUSIONS: This case highlights the diagnostic and therapeutic challenges of rare CE locations. MRI proved superior to CT in diagnosing bony cystic echinococcosis. Early surgical intervention combined with medication facilitates spinal cord function recovery, providing valuable insights for managing similar cases.

Strengthening China's National Essential Public Health Services Package for hypertension and diabetes care: protocol for an interrupted time series study with mixed-methods process evaluation and health economic evaluation.

BACKGROUND: Despite major primary health care (PHC) reforms in China with the 2009 launch of the National Essential Public Health Service Package, the country experiences many challenges in improving the management of non-communicable diseases in PHC facilities. "EMERALD" is a multifaceted implementation strategy to strengthen the management of hypertension and type-2 diabetes mellitus (T2DM) in PHC facilities. The study aims to: (1) examine the effectiveness of EMERALD in improving hypertension and T2DM management; (2) evaluate the implementation of the interventions; and (3) use the study findings to model the long-term health economic impact of the interventions. METHODS: The EMERALD intervention components include: (1) empowerment for PHC providers through training and capacity building; (2) empowerment for patient communities through multi-media health education; and  (3) empowerment for local health administrators through health data monitoring and strengthening governance of local PHC programs. An interrupted time series design will be used to determine the effectiveness of the interventions based on routinely collected health data extracted from local health information systems. The primary effectiveness outcome is the guideline-recommended treatment rates for people with hypertension and T2DM. Secondary effectiveness outcomes include hypertension and T2DM diagnosis and control rates, and enrolment and adherence rates to the recommended care processes in the National Essential Public Health Service Package. A mixed-methods process evaluation will be conducted to evaluate the implementation of the interventions, including the reach of the target population, adequacy of adoption, level of implementation fidelity, and maintenance. Qualitative interviews with policy makers, health administrators, PHC providers, and patients with hypertension and/or T2DM will be conducted to further identify factors influencing the implementation. In addition, health economic modelling will be performed to explore the long-term incremental costs and benefits of the interventions. DISCUSSION: This study is expected to generate important evidence on the effectiveness, implementation, and health economic impact of complex PHC interventions to strengthen the primary care sector's contribution to addressing the growing burden of non-communicable diseases in China. TRIAL REGISTRATION: The study has been registered on Chinese Clinical Trial Registry at https://www.chictr.org.cn/ (Registration number ChiCTR2400082036, on March 19th 2024).

Hsa_circ_0043533 modulates apoptosis and viability of granulosa cells via miR-409-3p/BCL2 and EMT signalling in PCOS: Providing novel perspective of metformin.

Polycystic ovary syndrome (PCOS) represents a significant cause of infertility among women of reproductive age. Studies have established a close association between granulosa cells (GCs) and the abnormal follicle formation and ovulation processes characteristic of PCOS. The interactions among hsa_circ_0043533, miR-409-3p, and BCL2 were verified through luciferase activity assays. In PCOS patients, granulosa cells exhibit notably reduced apoptosis but enhanced growth, leading to their accumulation and the development of polycystic ovaries. The involvement of non-coding RNAs in PCOS has been documented, with elevated levels of hsa_circ_0043533 observed in this condition. A comprehensive series of experiments were conducted to explore the role of hsa_circ_0043533 in PCOS and elucidate its underlying mechanisms. Silencing hsa_circ_0043533 was found to promote apoptosis and hinder the migration, proliferation, and viability of KGN cells. Furthermore, we uncovered the regulatory effects of hsa_circ_0043533 on the miR-409-3p/BCL2 axis and key markers of Epithelial-Mesenchymal Transition (EMT). Additionally, it was observed that metformin modulates the hsa_circ_0043533/miR-409-3p/BCL2 axis. Overall, this study provides novel insights into the molecular mechanisms regulating granulosa cell proliferation and apoptosis in PCOS, further elucidating the molecular pathogenesis of this condition.

Insights into the Flavor Profile of Yak Jerky from Different Muscles Based on Electronic Nose, Electronic Tongue, Gas Chromatography-Mass Spectrometry and Gas Chromatography-Ion Mobility Spectrometry.

It is well known that different muscles of yak exhibit distinctive characteristics, such as muscle fibers and metabolomic profiles. We hypothesized that different muscles could alter the flavor profile of yak jerky. Therefore, the objective of this study was to investigate the differences in flavor profiles of yak jerky produced by longissimus thoracis (LT), triceps brachii (TB) and biceps femoris (BF) through electronic nose (E-nose), electronic tongue (E-tongue), gas chromatography-mass spectrometry (GC-MS) and gas chromatography-ion mobility spectrometry (GC-IMS). The results indicated that different muscles played an important role on the flavor profile of yak jerky. And E-nose and E-tongue could effectively discriminate between yak jerky produced by LT, TB and BF from aroma and taste points of view, respectively. In particular, the LT group exhibited significantly higher response values for ANS (sweetness) and NMS (umami) compared to the BF and TB groups. A total of 65 and 47 volatile compounds were characterized in yak jerky by GC-MS and GC-IMS, respectively. A principal component analysis (PCA) model and robust principal component analysis (rPCA) model could effectively discriminate between the aroma profiles of the LT, TB and BF groups. Ten molecules could be considered potential markers for yak jerky produced by different muscles, filtered based on the criteria of relative odor activity values (ROAV) > 1, p < 0.05, and VIP > 1, namely 1-octen-3-ol, eucalyptol, isovaleraldehyde, 3-carene, D-limonene, γ-terpinene, hexanal-D, hexanal-M, 3-hydroxy-2-butanone-M and ethyl formate. Sensory evaluation demonstrated that the yak jerky produced by LT exhibited superior quality in comparison to that produced by BF and TB, mainly pertaining to lower levels of tenderness and higher color, taste and aroma levels. This study could help to understand the specific contribution of different muscles to the aroma profile of yak jerky and provide a scientific basis for improving the quality of yak jerky.

Quantifying attention in children with intellectual and developmental disabilities through multicenter electrooculogram signal analysis.

In a multicenter case-control investigation, we assessed the efficacy of the Electrooculogram Signal Analysis (EOG-SA) method, which integrates attention-related visual evocation, electrooculography, and nonlinear analysis, for distinguishing between intellectual and developmental disabilities (IDD) and typical development (TD) in children. Analyzing 127 participants (63 IDD, 64 TD), we applied nonlinear dynamics for feature extraction. Results indicated EOG-SA's capability to distinguish IDD, with higher template thresholds and Correlation Dimension values correlating with clinical severity. The template threshold proved a robust indicator, with higher values denoting severe IDD. Discriminative metrics showed areas under the curve of 0.91 (template threshold) and 0.85/0.91 (D2), with sensitivities and specificities of 77.6%/95.9% and 93.5%/71.0%, respectively. EOG-SA emerges as a promising tool, offering interpretable neural biomarkers for early and nuanced diagnosis of IDD.

Patient mistreatment, emotional exhaustion and work-family conflict among nurses: a moderated mediation model of social sharing of negative work events and perceived organizational support.

BACKGROUND: Nursing literature suggested that patient mistreatment has significant impacts on nurses' emotions and job burnout. Yet, further research is needed to understand the underlying mechanism and the spillover effect on nurses' families. Leveraging the goal progress theory, this study aimed to examine the association between patient mistreatment, nurses' emotional exhaustion, and work-family conflict, as well as the mediating role of social sharing of negative work events and the moderating role of perceived organizational support. METHODS: During the COVID-19 pandemic in China, a cross-sectional study was conducted with a sample of 1627 nurses from the Hematology Specialist Alliance of Chongqing from October to November 2022. Questionnaires were administered to measure patient mistreatment, perceived organizational support, social sharing of negative work events, emotional exhaustion, and work-family conflict. Hierarchical linear regression and conditional processes were used for statistical analyses. RESULTS: Patient mistreatment was positively associated with emotional exhaustion (ß = 0.354, p < 0.001) and work-family conflict (ß = 0.314, p < 0.001). Social sharing of negative work events played a partial mediating role in the relationship between patient mistreatment and emotional exhaustion (effect = 0.067, SE = 0.013), and work-family conflict (effect = 0.077, SE = 0.014). Moderated mediation analysis found that the mediation effect was stronger when the perceived organizational support was high. CONCLUSION: Our findings reveal the amplifying effect of social sharing of negative work events on nurses' emotional exhaustion and work-family conflict. Perceived organizational support strengthens the positive effect of patient mistreatment on the social sharing of negative work events, thus resulting in increased emotional exhaustion and work-family conflict. We also discuss practical implications, limitations, and directions for future research.

Effect of moxibustion on ATP-sensitive potassium channel (KATP) of bladder in detrusor overactivity rats. / 隔姜隔盐灸"神阙"å¯¹é€¼å°¿è‚Œè¿‡åº¦æ´»åŠ¨å¤§é¼ è†€èƒ±ATP敏感性钾离子通道的影响.

OBJECTIVES: To observe the effect of ginger-salt-partitioned moxibustion on ATP-sensitive potassium (KATP) channel of bladder in detrusor overactivity (DO) rats. METHODS: Female SD rats were randomly divided into sham operation, model, moxibustion and antagonist groups (n=9 in each group). Thorax (T) 10 spinal cord transection was performed by surgery. Ginger-salt partitioned moxibustion was applied to "Shenque" (CV8) for 3 cones, once daily for 14 consecutive days. Rats of the antagonist group were intraperitoneally injected with KATP channel specific antagonist glibenclamide (10 µg·kg-1·d-1) once daily for 14 consecutive days. Urodynamic tests were performed after treatment. The distribution and expression of KATP channel tetrameric subunit (SUR2B) in the bladder of rats was observed by immunofluorescence. The protein and mRNA expression levels of SUR2B in bladder tissue were detected by Western blot and qPCR respectively. RESULTS: Compared with the sham operation group, rats of the model group showed intensive and large phasic contractions of the detrusor during bladder filling, the frequency and amplitude of phasic contractions of the detrusor 5 min before leakage were significantly increased (P<0.001)；the voiding threshold pressure was significantly decreased (P<0.001)；the bladder perfusion volume was increased (P<0.001)；the SUR2B protein and mRNA expression in bladder tissue were significantly reduced (P<0.001). Compared with the model group and the antagonist group, the above-mentioned indicators in the moxibustion group were all reversed (P<0.01, P<0.001, P<0.05). CONCLUSIONS: Ginger-salt partitioned moxibustion can reduce the frequency and amplitude of detrusor phase contraction during bladder filling and prolong the time of first phase contraction in DO rats, which may be associated with up-regulating the expression level of KATP channel protein and mRNA, promoting the outflow of potassium ions, and inhibiting the inflow of calcium ions, thus improve the stability of detrusor during storage.

Construction of Yolk@shell Nanocomposite Particles with Controlled Multisized Pore Structures by Monomicelle Confined Assembly.

Hollow nanoparticles with tunable structures and spatial and chemical specificity are considered as promising carriers. However, it remains a formidable challenge to endow hollow nanomaterials with precisely controlled multisized macro/mesoporous structures up to now. This paper demonstrates a "polydopamine (PDA) expansion-shrinkage" strategy combined with a monomicelle interfacial confined assembly method to achieve the highly controllable preparation of a series of yolk@shell PDA@SiO2 composite nanoparticles with structural asymmetry and a tunable multisized pore in the shell. The strategy allows systematic manipulation of the average pore size of large slit pores in the range of 15.4-86.5 nm by adjusting the reaction temperature. Benefiting from advantages such as an asymmetric structure and multilevel porosity, they exhibit excellent performance in the applications of on-demand loading of dual-sized cargoes, dual-propelled nanomotors, and particle size-selected encapsulation and separation. These findings provide inspiration for the construction of asymmetric yolk@shell structures with tunable multisized pores for a wide range of biological and chemical applications.

Observation of the hexatic phase in a two-dimensional complex plasma using machine learning.

Complex plasmas consist of ionized gas and charged solid microparticles, representing the plasma state of soft matter. We apply machine learning methods to investigate a melting transition in a two-dimensional complex plasma. A convolutional neural network is constructed and trained with the numerical simulation. The hexatic phase is successfully identified and the evolution of topological defects is studied during melting transition in both simulations and experiments.

Effects of platelet-rich fibrin on human endometrial stromal cells behavior in comparison to platelet-rich plasma.

Introduction: Intrauterine transfusion of platelet-rich plasma (PRP) has become a new treatment for thin endometrium (TE) in recent years, but its low efficacy due to rapid release of growth factors limits its clinical use. Platelet-rich fibrin (PRF) starts the coagulation cascade reaction immediately after the blood comes into contact with the test tube. The natural coagulation process results in stable platelet activation and the slow release of growth factors. Methods: In our study, primary human endometrial stromal cells (hESCs) were extracted from endometrial tissue. PRP and PRF were prepared from the patient cubital vein blood. Stromal cells were cultured in conditioned medium supplemented with PRP and PRF. Differences in cell behavior were observed by cell proliferation test and cell migration test. The relative expression levels of apoptotic Bax and antiapoptotic Bcl-2 genes were measured by qRT-PCR. The release of growth factors from PRP and PRF was detected by ELISA. Results: We found that both PRP and PRF inhibited apoptosis of hESCs, which favored cell proliferation and migration. In addition, PRF releases growth factors for a longer period of time compared to PRP. Discussion: PRF offer a more sustained therapeutic effect compared to PRP, which provides a new idea for endometrial regeneration and repair.

Injectable GelMA Hydrogel Microspheres with Sustained Release of Platelet-Rich Plasma for the Treatment of Thin Endometrium.

Platelet-rich plasma (PRP) intrauterine infusion has been demonstrated to be effective in treating thin endometrium and achieving pregnancy. However, the rapid release of growth factors limits its effectiveness in clinical applications, and thus, multiple intrauterine infusions are often required to achieve therapeutic efficacy. In this study, a GelMA hydrogel microsphere biomaterial is developed using droplet microfluidics to modify the delivery mode of PRP and thus prolong its duration of action. Its biocompatibility is confirmed through both in vivo and in vitro studies. Cell experiments show that PRP-loaded microspheres significantly enhance cell proliferation, migration, and angiogenesis. In vivo experiments show that the effects of PRP-loaded microspheres on repairing the endometrium and restoring fertility in mice could achieve the impact of triple PRP intrauterine infusions. Further mechanistic investigations reveal that PRP could facilitate endometrial repair by regulating the expression of E2Fs, a group of transcription factors. This study demonstrates that hydrogel microspheres could modify the delivery of PRP and prolong its duration of action, enabling endometrial repair and functional reconstruction. This design avoids repeated intrauterine injections of PRP in the clinic, reduces the number of patient visits, and provides a new avenue for clinical treatment of thin endometrium.

A luminescent Cu2I2P2S2-type binuclear complex and its fluorescence sensing for pyridine.

Luminescent CuI complexes are an important class of coordination compounds due to their relative abundance, low cost and ability to display excellent luminescence. The title Cu2I2P2S2-type binuclear complex, di-µ-iodido-bis[(thiourea-κS)(triphenylphosphine-κP)copper(I)], [Cu2I2(CH4N2S)2(C18H15P)2], conventionally abbreviated as Cu2I2TPP2TU2, where TPP and TU represent triphenylphosphine and thiourea, respectively, is described. In this complex, each CuI atom adopts a CuI2PS four-coordination mode and pairs of atoms are connected to each other by two µ2-I ligands to form a centrosymmetric binuclear cluster. It was also found that the paper-based film of this complex exhibited obvious luminescence light-up sensing for pyridine and 4-methylpyridine.

From Novice to Mastery: Learning Curve and Efficacy Analysis of Short-Term Spinal Cord Stimulation for Diabetic Foot Ulcers.

BACKGROUND: To analyze the learning curve of novices in mastering short-term Spinal cord stimulation (st-SCS) for diabetic foot, evaluating the efficacy, safety, and difficulty of this technique. METHODS: A retrospective review of diabetic foot patients treated with st-SCS at our hospital was conducted. All procedures were performed by the same physician and patients were sequentially numbered according to the order of surgery. Learning curves were plotted using segmented linear regression and cumulative sum curves based on surgery duration. Patients were divided into 2 groups according to the inflection points on the learning curve: the learning group and the mastery group. Pre- and postoperative efficacy indicators were recorded and compared, along with general patient data, perioperative parameters, and incidence of complications. RESULTS: A total of 36 patients were included. Significant improvements were observed post-st-SCS in ulcer size (from 7.00 cm2 to 4.00 cm2), visual analog scale (from 7.00 to 3.00), foot temperature (from 30.06°C to 32.37°C), and Pittsburgh Sleep Quality Index (from 14.42 to 8.36) (P < 0.05). The physician could proficiently perform st-SCS after 9 cases. Surgery time was significantly shorter in the mastery group (1-9 cases) compared to the learning group (10-36 cases) (28.04 vs. 43.56 min, P < 0.05). There were no significant differences between the 2 groups in baseline data, improvement in efficacy indicators, or complications (P > 0.05). CONCLUSIONS: St-SCS is beneficial for wound healing, pain relief, improving peripheral circulation, and improving sleep quality. Surgeons can master this simple and safe technique in about 9 cases.

Application patterns and outcomes of hematopoietic stem cell transplantation in peripheral T-cell lymphoma patients: a multicenter real-world study in China.

The optimal timing and type of hematopoietic stem cell transplantation (HSCT) for treating peripheral T-cell lymphoma (PTCL) remain controversial. This retrospective real-world study investigated the application pattern and outcomes of HSCT in China. The analysis encompassed 408 PTCL patients with a median age of 45.5 years, all of whom received initial adequate therapy at five hospitals. Among patients with nodal PTCL who responded effectively to first-line therapy (the "responders", n = 127) and subsequently underwent HSCT consolidation (n = 47, 37.0%), 93.6% received auto-HSCT, while 6.4% underwent allo-HSCT. Front-line auto-HSCT showed potential for long-term disease control in nodal PTCL responders. Among non-nodal PTCL responders (n = 80) with HSCT (n = 26, 32.5%), 46.2% underwent allo-HSCT and 53.8% received auto-HSCT. Upfront allo-HSCT provides longer progression-free survival (PFS) for non-nodal PTCL responders, with lower 3-year cumulative incidence of relapse (CIR) (16.7% vs. 56.0%) and comparable non-relapse mortality (NRM) (10.4% vs. 11.0%) compared to auto-HSCT. For patients who achieved remission with second-line salvage regimens, allo-HSCT was the primary choice (82.4%) for non-nodal PTCL, while auto-HSCT was more common (82.4%) in nodal PTCL. Nodal PTCL patients underwent auto-HSCT after ≥ 3 lines of treatment had a higher 3-year CIR (81.0%) compared to those treated in the first (26.0%) or second line (26.0%). Non-nodal PTCL patients underwent allo-HSCT after ≥ 3 lines had a higher 3-year NRM (37.5%) compared to after first (10.4%) or second line treatment (8.5%). These findings highlight distinct HSCT application patterns for PTCL in China, emphasizing the impact of early disease control and upfront consolidative HSCT.