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.

Background The prevalence of low back pain among workers using vibrating tools in the automobile manufacturing industry is high; however, research on associated risk factors remains limited. Objective To investigate the association between use of vibrating tools and low back pain among automobile manufacturing workers, and to estimate related population attributable risk percentage (PAR%). Methods A cross-sectional survey was conducted using the Chinese Musculoskeletal Disorders Questionnaire among workers with over one year of service in an automobile manufacturing enterprise. Workers were categorized into an exposed group (vibrating tool users) and a control group (non-users) based on their use of vibrating tools during work. The variables showing statistically significant differences between the two groups were selected as covariates for matching by 1∶2 nearest-neighbor propensity score. Chi-square test was used to compare the prevalence of low back pain between the matched exposed and control groups. Log-binomial regression model was employed to calculate the prevalence ratio (PR), and the PAR% of low back pain attributable to vibrating tool use was subsequently determined. Results A total of 6973 valid questionnaires were collected, comprising 5676 males and 1297 females, with an overall low back pain prevalence of 40.3% (2809/6973). The exposed group included 1255 workers (1134 males, 121 females), with a mean age of (44.2 ± 8.7) years and a mean tenure in the current position of (23.5 ± 9.9) years; the matching control group consisted of 2510 workers (2279 males, 231 females), with a mean age of (44.7 ± 8.6) years and a mean tenure in the current position of (24.0 ± 10.0) years. The prevalence of low back pain was 76.7% (963/1255) in the exposed group, significantly higher than the 29.9% (750/2510) in the control group (P<0.001). The log-binomial regression analysis showed a PR of 2.57 (95%CI: 2.28, 2.90) for the exposed group, with a PAR% of 22.03%. Conclusion The use of vibrating tools among automobile manufacturing workers is positively associated with reporting low back pain. Implementing effective measures to mitigate vibration hazards is crucial for reducing the burden of low back pain in this population.

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

OBJECTIVE: To investigate the clinical phenotypic and genetic characteristics of three children with Paroxysmal kinesigenic dyskinesia (PKD) and Self-limited familial infantile epilepsy (SeLIE) caused by PRRT2 gene mutation. METHODS: Three children with PKD and SeLIE caused by PRRT2 gene mutation (children 1-3) who were treated in the First Affiliated Hospital of Zhengzhou University from November 2022 to August 2023 were selected as the research subjects. A retrospective study was conducted to collect the clinical and family history data of the three children. 2 mL of peripheral venous blood from children 1-3 and parents of children 1-2 were collected (parents of children refused to undergo genetic testing and no blood samples were collected), genomic DNA was extracted, whole exome sequencing (WES) was performed, and Sanger sequencing method was used for verification. According to the Classification Standards and Guidelines for Genetic Variants formulated by the American Society of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines"), the pathogenicity of the variant loci detected in three children was rated, and the detrimental loci of the variant loci were analyzed by multiple bioinformatics software. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2024-KY-0881-002). RESULTS: The clinical data and genetic test results of the three children in this study are as follows. Child 1: female, age of onset of 4 months and 10 days, with seizures, manifested as sudden cessation of movements, staring in both eyes, cyanosis of the lips, paleness, and stiffness and shaking of limbs. The results of genetic testing showed that child 1 had maternal PRRT2 gene c.583_584dup (p.P196Afs*34) frameshift variant, which was rated as a pathogenic variant (PVS1 PM2_Supporting PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 1, he was diagnosed with SeLIE and took oral sodium valproate [0.5 mL/(kg.d)], and was still taking medication at the follow-up of 2 years old, and did not have seizures again after 5 months of age. Child 2: male, age of onset of 10 years old, manifested as dystonia after sudden movement. The results of genetic testing showed that child 2 had PRRT2 gene mutations: paternal c.649dupC (p.R217Pfs*8) frameshift variant and maternal c.445C>A (p.Q149K) mutation. Among them, c.649dupC was a reported pathogenic variant, and according to ACMG guidelines, c.445C>A variant was rated as a variant of unknown clinical significance (PM2_Supporting), with a high probability of benignness. According to the clinical manifestations and genetic test results of the child 2, he was diagnosed with PKD, and was followed up with oral oxcarbazepine 9 mg/(kg.d) until 12 years and 2 months, and was still on the drug, and there was no recurrence of the seizure of the form of dyskinesia after taking the drug. Child 3: male, age of onset of 11 years old, manifested by dystonia after sudden exercise. The results of genetic testing showed that child 3 had a missense variant of PRRT2 gene c.904G>C (p.D302H), and his parents refused genetic testing, and the source of the mutation was unknown, and the variant was rated as a variant of unknown clinical significance (PM2_Supporting+PP3_Moderate+PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 3, he was diagnosed with PKD, and was treated with oral oxcarbazepine 10 mg/(kg.d) for 1 year and then discontinued on his own, and was followed up at the age of 17, and there was no recurrence of the seizure of the form of movement disorder after taking the drug. CONCLUSION One case of SeLIE and two cases of PKD caused by PRRT2 gene mutations responded well to anti-seizure drugs. In this study, four variant loci of PRRT2 gene were found: c.583_584dup, c.904G>C, c.649dupC, c.445C>A, among which c.583_584dup were new variants, enriching the variant spectrum of PRRT2 gene.
Humans ; Male ; Nerve Tissue Proteins/genetics* ; Female ; Membrane Proteins/genetics* ; Mutation ; Child, Preschool ; Infant ; Phenotype ; Dystonia/genetics* ; Retrospective Studies ; Child

OBJECTIVE: To analyze the clinical characteristics and genetic etiology of a child with Christianson syndrome (CS). METHODS: A 1-year-and-5-month-old boy with CS diagnosed at the First Affiliated Hospital of Zhengzhou University in April 2021 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral blood samples were obtained from the child and his parents, followed by genomic DNA extraction and whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the Hospital of Zhengzhou University (Ethics No. 2024-KY-1103-001). RESULTS: The child has manifested with seizures, microcephaly, and global developmental delay. WES revealed that he has harbored a novel de novo hemizygous nonsense variant of the SLC9A6 gene, namely c.1014G>A (p.W338*). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic. CONCLUSION The hemizygous c.1014G>A nonsense variant of the SLC9A6 gene probably underlay the pathogenesis in this child. Above discovery has expanded mutational spectrum of the SLC9A6 gene and enabled definite diagnosis of the child.
Humans ; Male ; Infant ; Microcephaly/genetics* ; Spasms, Infantile/genetics* ; Sodium-Hydrogen Exchangers/genetics* ; Exome Sequencing ; Intellectual Disability/genetics* ; Genetic Diseases, X-Linked/genetics* ; Mutation ; Seizures/genetics* ; Ataxia ; Epilepsy ; Ocular Motility Disorders

Objective To analyze challenges in translating exercise management evidence for patients with metabolism-associated fatty liver disease(MAFLD),develop actionable strategies,and evaluate the application of best evidence.Methods Utilizing the evidence translation model,the best evidence was implemented for MAFLD patients in 4 phases:evidence acquisition,baseline practice review,intervention,and outcome evaluation.We compared the knowledge of exercise management evidence,implementation rates of review indicators,completion of exercise programs,BMI,liver stiffness measurement,controlled attenuation parameters,and patient satisfaction among medical staff at a tertiary hospital in Fujian Province during baseline(March-May 2023),mid-practice(June-August 2023),and late-practice(September-November 2023)phases.Results A total of 88 patients were included at baseline review,95 during mid-practice,and 107 in late-practice.Significant improvements were observed in the implementation rates of 21 review indicators,nurses'knowledge,completion rate,BMI,and controlled attenuation parameters compared to the data at baseline(P＜0.05).Conclusion The application of best evidence in exercise management for MAFLD patients enhances nurses'knowledge,standardizes nursing practices,and reduces patients'BMI and controlled attenuation parameters.

Objective:To investigate the clinical phenotypic and genetic characteristics of three children with Paroxysmal kinesigenic dyskinesia (PKD) and Self-limited familial infantile epilepsy (SeLIE) caused by PRRT2 gene mutation. Methods:Three children with PKD and SeLIE caused by PRRT2 gene mutation (children 1-3) who were treated in the First Affiliated Hospital of Zhengzhou University from November 2022 to August 2023 were selected as the research subjects. A retrospective study was conducted to collect the clinical and family history data of the three children. 2 mL of peripheral venous blood from children 1-3 and parents of children 1-2 were collected (parents of children refused to undergo genetic testing and no blood samples were collected), genomic DNA was extracted, whole exome sequencing (WES) was performed, and Sanger sequencing method was used for verification. According to the Classification Standards and Guidelines for Genetic Variants formulated by the American Society of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines" ), the pathogenicity of the variant loci detected in three children was rated, and the detrimental loci of the variant loci were analyzed by multiple bioinformatics software. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2024-KY-0881-002). Results:The clinical data and genetic test results of the three children in this study are as follows. ①Child 1: female, age of onset of 4 months and 10 days, with seizures, manifested as sudden cessation of movements, staring in both eyes, cyanosis of the lips, paleness, and stiffness and shaking of limbs. The results of genetic testing showed that child 1 had maternal PRRT2 gene c. 583_584dup (p. P196Afs*34) frameshift variant, which was rated as a pathogenic variant (PVS1 PM2_Supporting PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 1, he was diagnosed with SeLIE and took oral sodium valproate [0.5 mL/(kg.d)], and was still taking medication at the follow-up of 2 years old, and did not have seizures again after 5 months of age. ②Child 2: male, age of onset of 10 years old, manifested as dystonia after sudden movement. The results of genetic testing showed that child 2 had PRRT2 gene mutations: paternal c. 649dupC (p.R217Pfs*8) frameshift variant and maternal c. 445C>A (p.Q149K) mutation. Among them, c. 649dupC was a reported pathogenic variant, and according to ACMG guidelines, c. 445C>A variant was rated as a variant of unknown clinical significance (PM2_Supporting), with a high probability of benignness. According to the clinical manifestations and genetic test results of the child 2, he was diagnosed with PKD, and was followed up with oral oxcarbazepine 9 mg/(kg.d) until 12 years and 2 months, and was still on the drug, and there was no recurrence of the seizure of the form of dyskinesia after taking the drug. ③Child 3: male, age of onset of 11 years old, manifested by dystonia after sudden exercise. The results of genetic testing showed that child 3 had a missense variant of PRRT2 gene c. 904G>C (p.D302H), and his parents refused genetic testing, and the source of the mutation was unknown, and the variant was rated as a variant of unknown clinical significance (PM2_Supporting+ PP3_Moderate+ PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 3, he was diagnosed with PKD, and was treated with oral oxcarbazepine 10 mg/(kg.d) for 1 year and then discontinued on his own, and was followed up at the age of 17, and there was no recurrence of the seizure of the form of movement disorder after taking the drug. Conclusion:One case of SeLIE and two cases of PKD caused by PRRT2 gene mutations responded well to anti-seizure drugs. In this study, four variant loci of PRRT2 gene were found: c. 583_584dup, c. 904G>C, c. 649dupC, c. 445C>A, among which c. 583_584dup were new variants, enriching the variant spectrum of PRRT2 gene.

Objective:To analyze the clinical characteristics and genetic etiology of a child with Christianson syndrome (CS).Methods:A 1-year-and-5-month-old boy with CS diagnosed at the First Affiliated Hospital of Zhengzhou University in April 2021 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral blood samples were obtained from the child and his parents, followed by genomic DNA extraction and whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-KY-1103-001).Results:The child has manifested with seizures, microcephaly, and global developmental delay. WES revealed that he has harbored a novel de novo hemizygous nonsense variant of the SLC9A6 gene, namely c. 1014G>A (p.W338*). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic. Conclusion:The hemizygous c. 1014G>A nonsense variant of the SLC9A6 gene probably underlay the pathogenesis in this child. Above discovery has expanded mutational spectrum of the SLC9A6 gene and enabled definite diagnosis of the child.

Objective To analyze challenges in translating exercise management evidence for patients with metabolism-associated fatty liver disease(MAFLD),develop actionable strategies,and evaluate the application of best evidence.Methods Utilizing the evidence translation model,the best evidence was implemented for MAFLD patients in 4 phases:evidence acquisition,baseline practice review,intervention,and outcome evaluation.We compared the knowledge of exercise management evidence,implementation rates of review indicators,completion of exercise programs,BMI,liver stiffness measurement,controlled attenuation parameters,and patient satisfaction among medical staff at a tertiary hospital in Fujian Province during baseline(March-May 2023),mid-practice(June-August 2023),and late-practice(September-November 2023)phases.Results A total of 88 patients were included at baseline review,95 during mid-practice,and 107 in late-practice.Significant improvements were observed in the implementation rates of 21 review indicators,nurses'knowledge,completion rate,BMI,and controlled attenuation parameters compared to the data at baseline(P＜0.05).Conclusion The application of best evidence in exercise management for MAFLD patients enhances nurses'knowledge,standardizes nursing practices,and reduces patients'BMI and controlled attenuation parameters.