OBJECTIVE To systematically analyze the trends in the volume and value of out-licensing deals by Chinese biopharmaceutical companies over the past two decades， and to quantitatively identify factors associated with deal value， thereby providing an evidence base for policymakers and corporate managers. METHODS Based on the PharnexCloud database， information on out-licensing deals disclosed by Chinese biopharmaceutical companies between January 1， 2005 and December 31， 2025 was collected， and executed deals with disclosed specific financial terms were included for analysis. Descriptive statistical analyses of deal value， product characteristics and deal characteristics were performed using Stata SE 18.0； with the natural logarithm of deal value as the dependent variable， stepwise multiple regression models were constructed to examine the associations of product and deal characteristics with deal value. RESULTS A total of 210 out-licensing deals were included， with a cumulative deal value of approximately 214.151 billion dollars and a mean deal value of 1.020 billion dollars . The trading market expanded rapidly from 2020 onward， with the annual deal value reaching a record 95.687 billion dollars in 2025. Multiple regression analysis showed that the deal value of products at the drug discovery stage was significantly lower than that at the preclinical stage [regression coefficient （ β ） ＝－1.995， 95% confidence interval （CI）： －3.256 to －0.734， P ＜0.05 ] ； the deal value of oncology products was significantly higher than that of other therapeutic areas （ β ＝0.828， 95%CI： 0.224 to 1.431， P ＜0.05）； global licensing （ β ＝1.690， 95%CI： 1.107 to 2.273， P ＜0.05） and co-development arrangements （ β ＝0.849， 95%CI： 0.084 to 1.615， P ＜0.05） were significantly associated with higher deal value. CONCLUSIONS Out-licensing deals by Chinese biopharmaceutical companies have achieved significant growth in both volume and value over the past two decades. Oncology products， global licensing， and co-development arrangements are significantly and positively associated with higher deal value.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Objective:To investigate the correlation between serum growth differentiation factor 15 (GDF15) and the clinicopathological characteristics of patients with IgA nephropathy (IgAN), and further explore the relationship of GDF15 with the cardiac and renal prognosis of IgAN patients.Methods:It was a single-center retrospective cohort study. From January 2018 to December 2022, the relevant data were collected from patients who were diagnosed with primary IgAN at the Department of Nephrology, Beijing Anzhen Hospital Affiliated to Capital Medical University, and regularly followed up for at least 1 year. Serum samples were collected at admission and the baseline level of serum GDF15 was measured. Based on the median GDF15 level, IgAN patients were categorized into high-level GDF15 group and low-level GDF15 group, and their clinicopathological characteristics were compared. A multiple linear regression model was then constructed to identify independent factors associated with serum GDF15 level based on these comparisons. Subsequently, Kaplan-Meier survival analysis was performed to investigate the association between serum GDF15 level and the cardiorenal prognosis of IgAN patients.Results:A total of 104 IgAN patients were included in this study. The serum GDF15 level in these IgAN patients was 825.60 (556.84, 1 428.15) ng/L. Serum GDF15 level was positively correlated with 24 h urinary protein ( r=0.405, P<0.001), negatively correlated with estimated glomerular filtration rate (eGFR)( r=-0.606, P<0.001). The serum levels of GDF15 in patients with tubular atrophy or interstitial fibrosis (overall comparison among T0, T1, and T2, H=21.866, P<0.001), crescentic lesions (overall comparison among C0, C1, and C2, H=13.787, P=0.001), or intrarenal arteriolar lesions (overall comparison among none, mild, and moderate-to-severe, H=9.856, P=0.007) were significantly different. Compared with IgAN patients without tubular atrophy or interstitial fibrosis, those with Oxford classification T1 ( Z=-17.326, P=0.042) or T2 ( Z=-42.933, P<0.001) had higher serum GDF15 levels. Compared with IgAN patients without crescentic lesions, those with Oxford classification C2 had higher serum GDF15 levels ( Z=-45.929, P=0.001). Compared with IgAN patients without intrarenal arteriolar lesions, those with moderate-to-severe arteriolar sclerosis had higher serum GDF15 levels ( Z=-26.686, P=0.005). The median GDF15 was used as the cut-off value to divide IgAN patients into a high-level GDF15 group (≥825.60 ng/L, n=52) and a low-level GDF15 group (<825.60 ng/L, n=52). Compared to low-level GDF15 group, IgAN patients in high-level GDF15 group presented with a higher proportion of diabetes mellitus ( χ 2=9.420, P=0.002) and cardiovascular disease ( χ 2=7.792, P=0.005), a higher level of systolic blood pressure ( Z=-2.266, P=0.023), body mass index ( Z=-2.183, P=0.031), 24 h urinary protein ( Z=-3.485, P<0.001), blood total cholesterol ( Z=-2.002, P=0.045) and left ventricular mass index ( Z=-2.649, P=0.008), and a lower level of blood albumin ( Z=-3.053, P=0.002) and eGFR ( Z=6.480, P<0.001). Multiple linear regression analysis showed that serum GDF15 level was independently associated with systolic blood pressure (regression coefficient B=29.453, 95% CI 14.139–44.767, P<0.001), blood albumin ( B=-81.412, 95% CI -113.084–-49.740, P<0.001) and eGFR ( B=-9.797, 95% CI -17.554–-2.040, P=0.014). Moreover, IgAN patients in high-level GDF15 group exhibited significantly poorer cardiac and renal prognosis compared to low-level GDF15 group ( χ 2=9.955, P=0.002). Conclusion:High serum GDF15 level correlates with disease severity in IgAN, and high serum GDF15 level may suggest a poorer cardiorenal prognosis in IgAN patients.

Rehabilitation is an effective measure to improve the quality of life for cancer patients,and strong rehabilitation motivation is an important influencing factor for patients' compliance with rehabilitation.This paper mainly reviews the concepts,assessment tools,influencing factors,and intervention strategies of rehabilitation motivation in cancer patients,with the aim of providing references for medical staff to improve the level of rehabilitation compliance in cancer patients and develop targeted rehabilitation management strategies.

Objective To systematically evaluate the rehabilitation effect of immersive virtual reality technology for patients with peripheral vestibular dysfunction,and to provide theoretical basis and practical guidance for the design of efficient rehabilitation training programs.Methods PubMed,Embase,Cochrane Library,Web of Science,CINAHL,CNKI,Wanfang Database,VIP Database,and China Biomedical Literature Database were searched for randomized controlled trials on the intervention effect of immersive virtual reality technology in patients with peripheral vestibular dysfunction from inception to February 2025.RevMan5.4 software was used to perform meta-analysis of the literature that met the quality standards.Results A total of 10 papers with 491 patients with peripheral vestibular dysfunction were included.Meta-analysis showed that immersive virtual reality technology improved vertigo symptoms in patients with peripheral vestibular dysfunction compared with conventional vestibular rehabilitation care[SMD=-1.41,95％CI(-1.58,-0.70),P＜0.001],and subgroup analysis showed that the frequency of intervention was＜5 times/week[SMD=-1.31,95％CI=(-1.96,-0.66),P＜0.001],single intervention duration＜30 min[SMD=-1.45,95％CI=(-2.21,-0.70),P＜0.001],and intervention period≤7 weeks[SMD=-1.49,95％CI(-2.04,-0.94),P＜0.001]were more significant.Immersive virtual reality technology reduced the risk of falls[MD=4.66,95％CI(3.84,5.48),P＜0.001],and improved anxiety and depression[SMD=2.65,95％CI(1.98,3.33),P＜0.001].Conclusion Immer-sive virtual reality technology improves vertigo symptoms,reduces the risk of falls,and improves anxiety and depres-sion symptoms in patients with peripheral vestibular dysfunction,in which the intervention period of ≤7 weeks,＜5 training sessions per week,and each training session of＜30 min are better for improving vertigo symptoms in patients with peripheral vestibular dysfunction.

Objective To investigate the role and biological mechanism of exosomal miRNA-141-3p in inducing the proliferation and invasion of prostate cancer(PCa)cells.Methods The expression level of miR-NA-141-3p in tumor tissues and adjacent tissues from 33 PCa patients,as well as in exosomes of human PCa cells VCap and normal prostate cells RWPE-2,was analyzed using quantitative real-time PCR(qPCR).The di-rect target of miRNA-141-3p was predicted through bioinformatic analysis and verified using a dual-luciferase reporter gene assay.miRNA-141-3p inhibitor plasmid(miRNA-141-3p inhibitor group)and negative control plasmid(negative control group)were transfected into human PCa cells VCap via lipofection.Cell prolifera-tion,migration,and invasion abilities in the miRNA-141-3p inhibitor group and negative control group were detected using MTT assay,wound healing assay,and Transwell assay,respectively.The mRNA expression levels of PHLPP2,E-Cadherin,and Vimentin were measured by qPCR,and the protein expression levels by Western blot,in VCap and RWPE-2 cells as well as in the miRNA-141-3p inhibitor group and negative control group.Results The expression level of exosomal miRNA-141-3p in tumor tissues was significantly higher than in adjacent tissues(P<0.05).Dual-luciferase reporter assay confirmed that PHLPP2 is the direct target gene of miRNA-141-3p.The expression levels of exosomal PHLPP2,E-Cadherin mRNA and protein in VCap cells were lower than in RWPE-2 cells,while the expression levels of Vimentin mRNA and protein were high-er than in RWPE-2 cells,with statistically significant intergroup differences(P=0.012).In the miR-141-3p inhibitor group,exosomal miR-141-3p,Vimentin mRNA expression level,cell proliferation rate(MTS assay),migrating cell count(scratch assay),and transmembrane cell count(Transwell invasion assay)were signifi-cantly decreased compared to the negative control group,while PHLPP2 mRNA and E-Cadherin mRNA ex-pression levels were significantly increased,with statistically significant intergroup differences(P<0.05).Conclusion miR-141-3p promotes proliferation and migration of human PCa cells by targeting PHLPP2.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Complement C3 plays a critical role in periodontitis. However, its source, role and underlying mechanisms remain unclear. In our study, by analyzing single-cell sequencing data from mouse model of periodontitis, we identified that C3 is primarily derived from periodontal fibroblasts. Subsequently, we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis. C3ar^-/- mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice, characterized by mild gingival tissue damage and reduced alveolar bone loss. This reduction was associated with decreased production of pro-inflammatory mediators and reduced osteoclast infiltration in the periodontal tissues. Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation. Finally, by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis, we found that the results observed in mice were consistent with human data. Therefore, our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis, driven by macrophage M1 polarization and osteoclast differentiation. These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
Animals ; Osteoclasts/cytology* ; Periodontitis/metabolism* ; Cell Differentiation ; Mice ; Fibroblasts/metabolism* ; Macrophages ; Disease Models, Animal ; Complement C3/metabolism* ; Humans ; Disease Progression ; Mice, Inbred C57BL ; Male ; Mice, Knockout

OBJECTIVE: To observe the characteristics of changes in non-invasive hemodynamic parameters in neonates with septic shock so as to provide clinical reference for diagnosis and treatment. METHODS: A observational study was conducted. The neonates with sepsis complicated with septic shock or not admitted to neonatal intensive care unit (NICU) of the First Affiliated Hospital of Shantou University Medical College were enrolled as the study subjects, who were divided into preterm infant (< 37 weeks) and full-term infant (≥ 37 weeks) according to the gestational age. Healthy full-term infants and hemodynamically stable preterm infants transferring to NICU after birth were enrolled as controls. Electronic cardiometry (EC) was used to measure hemodynamic parameters, including heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), stroke volume index (SVI), cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR) and systemic vascular resistance index (SVRI), before treatment in the septic shock group, at the time of diagnosis of sepsis in the sepsis without shock group, and before the discharge from the obstetric department or on the day of transferring to NICU in the control group. RESULTS: Finally, 113 neonates with complete data and parental consent for non-invasive hemodynamic monitoring were enrolled, including 32 cases in the septic shock group, 25 cases in the sepsis without shock group and 56 cases in the control group. In the septic shock group, there were 17 cases at the compensated stage and 15 cases at the decompensated stage. There were 21 full-term infants (20 cured or improved and 1 died) and 11 premature infants (7 cured or improved and 4 died), with the mortality of 15.62% (5/32). There were 18 full-term infants and 7 premature infants in the sepsis without shock group and all cured or improved without death. The control group included 28 full-term infants and 28 premature infants transferring to NICU after birth. Non-invasive hemodynamic parameter analysis showed that SV, SVI, CO and CI of full-term infants in the septic shock group were significantly lower than those in the sepsis without shock group and control group [SV (mL): 3.52±0.99 vs. 5.79±1.32, 5.22±1.02, SVI (mL/m²): 16.80 (15.05, 19.65) vs. 27.00 (22.00, 32.00), 27.00 (23.00, 29.75), CO (L/min): 0.52±0.17 vs. 0.80±0.14, 0.72±0.12, CI (mL×s^-1×m^-2): 40.00 (36.67, 49.18) vs. 62.51 (56.34, 70.85), 60.01 (53.34, 69.68), all P < 0.05], while SVR and SVRI were significantly higher than those in the sepsis without shock group and control group [SVR (kPa×s×L^-1): 773.46±291.96 vs. 524.17±84.76, 549.38±72.36, SVRI (kPa×s×L^-1×m^-2): 149.27±51.76 vs. 108.12±12.66, 107.81±11.87, all P < 0.05]. MAP, SV, SVI, CO and CI of preterm infants in the septic shock group were significantly lower than those in the control group [MAP (mmHg, 1 mmHg ≈ 0.133 kPa): 38.55±10.48 vs. 47.46±2.85, SV (mL): 2.45 (1.36, 3.58) vs. 3.96 (3.56, 4.49), SVI (mL/m²): 17.60 (14.20, 25.00) vs. 25.50 (24.00, 29.00), CO (L/min): 0.32 (0.24, 0.63) vs. 0.56 (0.49, 0.63), CI (mL×s^-1×m^-2): 40.01 (33.34, 53.34) vs. 61.68 (56.68, 63.35), all P < 0.05], while SVR and SVRI were similar to the control group [SVR (kPa×s×L^-1): 1 082.88±689.39 vs. 656.63±118.83, SVRI (kPa×s×L^-1×m^-2): 126.00±61.50 vs. 102.37±11.68, both P > 0.05]. Further analysis showed that SV, SVI and CI of neonates at the compensation stage in the septic shock group were significantly lower than those in the control group [SV (mL): 3.60±1.29 vs. 4.73±1.15, SVI (mL/m²): 19.20±8.33 vs. 26.34±3.91, CI (mL×s^-1×m^-2): 46.51±20.34 vs. 61.01±7.67, all P < 0.05], while MAP, SVR and SVRI were significantly higher than those in the control group [MAP (mmHg): 52.06±8.61 vs. 48.54±3.21, SVR (kPa×s×L^-1): 874.95±318.70 vs. 603.01±111.49, SVRI (kPa×s×L^-1×m^-2): 165.07±54.90 vs. 105.09±11.99, all P < 0.05]; MAP, SV, SVI, CO and CI of neonates at the decompensated stage in the septic shock group were significantly lower than those in the control group [MAP (mmHg): 35.13±6.08 vs. 48.54±3.21, SV (mL): 2.89±1.17 vs. 4.73±1.15, SVI (mL/m²): 18.50±4.99 vs. 26.34±3.91, CO (L/min): 0.41±0.19 vs. 0.65±0.15, CI (mL×s^-1×m^-2): 43.34±14.17 vs. 61.01±7.67, all P < 0.05], while SVR and SVRI were similar to the control group [SVR (kPa×s×L^-1): 885.49±628.04 vs. 603.01±111.49, SVRI (kPa×s×L^-1×m^-2): 114.29±43.54 vs. 105.09±11.99, both P > 0.05]. CONCLUSIONS Full-term infant with septic shock exhibit a low cardiac output, high vascular resistance hemodynamic pattern, while preterm infant with septic shock show low cardiac output and normal vascular resistance. At the compensated stage the hemodynamic change is low output and high resistance type, while at the decompensated stage it is low output and normal resistance type. Non-invasive hemodynamic monitoring can assist in the identification of neonatal septic shock and provide basis for clinical diagnosis and treatment.
Humans ; Shock, Septic/physiopathology* ; Infant, Newborn ; Hemodynamics ; Female ; Male ; Case-Control Studies ; Infant, Premature