撰文丨王聪 编辑丨王多鱼 排版丨水成文 实体瘤 的治疗耐受性常源于癌细胞中同源重组 （ Homologous Recombination， HR） 修复能力的增强，但该通路的系统性调控机制尚不明确。 2025 年 12 月 17 日， 中山大学中山医学院 潘超云 团队联合中山大学附属第一医院 刘军秀 / 李洁 团队及华中科技大学同济医院 高庆蕾 团队 （ 李洁 、 卢靖 怡 、 郑翠苗 、 黄茜 、 李浩源 为论文共同第一作者 ） ，在 Cell 子刊 Cell Metabolism 上发表了题为： Serotonin-licensed macrophages potentiate chemoresistance via inositol metabolic crosstalk in ovarian cancer 的研究。 该研究首次揭示外周 血清素 （5-HT） 通过肿瘤相关巨噬细胞 （TAM） 增强肿瘤细胞的 DNA 同源重组修复，导致卵巢癌化疗耐药的作用机制，并创新性地提 出将常用的 SSRI 类抗抑郁药物 氟西汀 作为化疗增敏剂的潜在治疗策略。 在这项最新研究中，研究团队发现了一类对 血清素 （5-H ...

10日，记者从合肥综合性国家科学中心大健康研究院获悉，该院曹灿、王春玉团队联合中国科学技术大 学薛天团队、天津医科大学陈贺团队等，提出一种快速抗抑郁新策略，并设计出候选化合物 TMU4142，该化合物在动物实验中呈现显著的快速抗抑郁效果，且无明显副作用，为研发新一代快速 抗抑郁药物提供了新思路。相关成果日前在线发表于国际期刊《细胞》。 在研发过程中，研究团队注意到前人研究中报道不同脑区血清素1A受体，在下游信号传递中会"偏 好"结合不同G蛋白类型来发挥功能，中缝背核受体主要与Gi3蛋白结合，而海马体及皮质区的受体则主 要结合GoA蛋白。团队据此提出新策略：设计一种"偏好"激活GoA蛋白的化合物，在维持对GoA蛋白激 活能力的同时，弱化其对Gi3蛋白的激活，从而精准调控有益通路、规避延迟起效的有害效应。 研究团队以具有部分GoA蛋白激活特性的老药Pindolol为参考分子骨架，优化并合成了新候选化合物 TMU4142。在新奇食物抑制实验中，TMU4142注射1小时即可改善小鼠抑郁状态。神经化学检测进一步 证实，该化合物在治疗剂量下不会引发中缝背核区域自身受体介导负反馈作用。 曹灿表示，团队下一步将持续优化化合物 ...

Group 1: Termination of Restructuring - The termination of the restructuring project was primarily due to changes in the overall market environment, which affected the expectations of the parties involved in the transaction [2][3][6] - The company decided to terminate the restructuring to protect the long-term interests of all shareholders after thorough discussions and analyses with relevant parties [2][6][8] Group 2: Market Environment and Strategic Focus - Recent changes in centralized procurement policies have altered the supply-demand relationship for drugs, impacting the expectations for the restructuring project [3] - The company remains focused on drug research, production, and sales, with a strong emphasis on developing new products and expanding its product range, including categories such as hypoglycemic, anesthetic, cardiovascular, and psychiatric drugs [3][5][7] Group 3: Financial Performance - For the period from January to September 2025, the company achieved a revenue of ¥302,688,076.14 and a net profit attributable to shareholders of ¥31,261,045.17 [5] - The company plans to continue investing in core products to enhance market share and profitability, especially in light of the upcoming procurement agreements [5][7] Group 4: Future Plans and Collaborations - The company is committed to exploring new product introductions and market development strategies following the termination of the restructuring [7][8] - Collaborations with research institutions and industry partners are planned to enhance technological cooperation and joint research efforts [4][8] Group 5: Market Position and Competitive Advantage - The company has established a strong market position with key products such as Glimepiride and Metformin, supported by advanced technology and mature production processes [7][8] - The company holds 31 active pharmaceutical ingredient (API) registration numbers and 44 approved chemical drug formulations, with many products included in national medical insurance directories [8]

Core Viewpoint - The article discusses the condition of obsessive-compulsive disorder (OCD) through the case of an 18-year-old college student, highlighting its symptoms, treatment options, and the importance of family support in the recovery process [1][2][8]. Summary by Sections Definition and Symptoms - OCD is characterized by obsessive thoughts and compulsive behaviors that significantly impact daily life, work, and relationships [2]. - Obsessive thoughts are intrusive ideas that cause excessive anxiety, while compulsive behaviors are repetitive actions aimed at reducing this anxiety [2]. Treatment Options - First-line treatments for OCD include medication and psychological therapy. Common medications include fluvoxamine, sertraline, paroxetine, and fluoxetine, while cognitive behavioral therapy (CBT) is the most recommended psychological treatment [3]. - Medication typically takes 4 to 6 weeks to show effects, with some initial side effects like dry mouth and drowsiness, which usually subside [3]. - CBT, particularly the exposure and response prevention (ERP) technique, is effective in helping patients manage their anxiety and regain control over their symptoms [5]. Integrated Treatment Approach - The hospital employs an individualized and integrated treatment model that combines medication, psychological therapy, physical therapy, and traditional Chinese medicine to maximize treatment effectiveness [7]. - Patients are encouraged to participate in group therapy and individual sessions to learn coping strategies and become their own therapists [7]. Family Involvement - Family support is crucial in the treatment of OCD, as family members can inadvertently enable the disorder by accommodating the patient's compulsive behaviors [8]. - Education for family members is provided to help them respond appropriately to the patient's symptoms and reduce the risk of relapse after discharge [8]. Additional Treatment Methods - Other treatment methods include physical therapies such as transcranial magnetic stimulation, relaxation techniques, and acupuncture, which complement medication and psychological therapy [9][10]. Recovery Potential - With dedicated effort from both patients and healthcare providers, most individuals with OCD can return to normal life. Long-term commitment to therapy, such as mindfulness practices, can lead to successful outcomes [12].

Core Viewpoint - The article discusses the challenges and considerations surrounding off-label drug use in pediatric patients, particularly for rare diseases, emphasizing the need to alleviate physicians' concerns regarding prescribing practices [1][3][6]. Group 1: Physician Concerns - Physicians are often conservative in their prescribing practices, especially for vulnerable populations like children, due to ethical and legal risks associated with off-label drug use [2][3]. - A significant percentage of doctors in Turkey and the U.S. avoid high-risk treatments, with estimates suggesting that around 50% of Chinese doctors may do the same, particularly in pediatric cases [1][2]. Group 2: Off-Label Drug Use - Off-label drug use is defined as using medications beyond the indications approved by regulatory authorities, which can include different dosages, routes of administration, or patient populations [3][5]. - There are two main categories of off-label drug use in pediatric rare diseases: high-cost innovative drugs and older, less expensive medications that may still provide benefits for rare conditions [4][5]. Group 3: Regulatory and Policy Framework - Recent guidelines and expert consensus have been developed to standardize off-label drug use in pediatric rare diseases, although there are still gaps in the regulatory framework [5][6]. - The National Health Commission has reiterated support for necessary off-label drug use, but reimbursement for such uses remains a challenge, as they are not typically covered by basic medical insurance [6][7]. Group 4: Research and Evidence - The expansion of drug indications for pediatric use often relies on real-world evidence, which is difficult to accumulate if physicians are hesitant to prescribe [3][8]. - Clinical trials for pediatric drugs face ethical challenges, leading to a reliance on adult data for pediatric applications, which complicates the approval process for new indications [7][9]. Group 5: Future Directions - There is a need for more patient-centered clinical trials to enhance data collection for pediatric rare diseases, as current methods often yield insufficient participant numbers [9][10]. - The industry is exploring innovative approaches to gather real-world evidence to support the expansion of drug indications for children, particularly in the context of rare diseases [9].

Core Viewpoint - The article discusses the challenges and considerations surrounding off-label drug use, particularly in pediatric patients with rare diseases, emphasizing the need to alleviate physicians' concerns regarding prescriptions [1][3][7]. Group 1: Physician Concerns - Physicians are hesitant to prescribe off-label medications due to concerns about ethical and legal implications, especially when treating vulnerable populations like children [2][4]. - A significant percentage of doctors in Turkey and the U.S. avoid high-risk treatments, with estimates suggesting around 50% in China, particularly for pediatric cases [2][3]. - The lack of evidence-based data for pediatric medications exacerbates physicians' reluctance to prescribe off-label treatments [3][4]. Group 2: Regulatory and Policy Framework - The National Health Commission supports reasonable off-label drug use when no better treatment options exist, provided that informed consent is obtained from patients [3][7]. - Recent guidelines and expert consensus have been published to standardize off-label drug use for pediatric rare diseases, addressing the absence of established protocols [5][7]. - Despite supportive policies, off-label drug use remains outside the scope of basic medical insurance coverage, placing financial burdens on patients [8]. Group 3: Drug Development and Research - The development of pediatric medications is hindered by ethical constraints in clinical trials, leading to a reliance on adult data for pediatric applications [8][9]. - The process of expanding drug indications for children is complex, often requiring extensive real-world data to demonstrate safety and efficacy [9][10]. - The pharmaceutical industry shows limited motivation to pursue new indications for pediatric use, making investigator-initiated trials (IIT) crucial for supporting new indications [9][10].

Summary of Kanghong Pharmaceutical Conference Call Company Overview - **Company**: Kanghong Pharmaceutical - **Date**: August 28, 2025 Key Industry Insights - **R&D Investment**: Significant increase in R&D spending, with a 16.45% year-over-year rise. Capitalized R&D expenses surged by 440% due to the Alzheimer's treatment product KH110 entering Phase III clinical trials [2][3][20]. - **Market Dynamics**: The ophthalmology market is evolving, with Kanghong's product, Conbercept, holding a 52% market share. The market is transitioning to a competitive landscape involving Conbercept, Aflibercept, and Ranibizumab, with upcoming negotiations on medical insurance expected to impact future market conditions [2][9][8]. Financial Performance - **Revenue Growth**: In the first half of 2025, Kanghong achieved a revenue growth of 6.95% and a net profit increase of 5.15% [3][22]. - **Segment Performance**: The biological drug segment showed a robust growth of 14.66%, while the chemical drug segment faced a decline of nearly 15% due to centralized procurement impacts [3][6]. Product Development and Pipeline - **Conbercept**: Expected to maintain steady growth despite competition from biosimilars. New technology platforms are entering clinical stages, contributing to optimistic performance forecasts for the year and next [4][5]. - **Gene Therapy Products**: Two gene therapy products, 631 and 658, are progressing well in clinical trials, showing good safety profiles and effectiveness compared to existing treatments [10][11][13]. - **Alzheimer's Product KH120**: Currently in Phase III clinical trials in China, with expectations for market entry in 2026. The product's multi-target characteristics may yield favorable outcomes, although sales forecasts remain uncertain [4][26]. Challenges and Strategic Responses - **Impact of Centralized Procurement**: The chemical drug segment has been significantly affected by price reductions due to centralized procurement, with recovery expected in two years. New products for dry eye syndrome are set to launch in the second half of the year to mitigate revenue losses [6][20]. - **Management and R&D Expenses**: Sales and management expenses showed modest growth, while R&D expenses increased significantly. The company anticipates maintaining a high level of R&D investment as more products enter advanced clinical stages [20][21]. Future Outlook - **Sales and Profit Growth**: The company maintains a revenue and profit growth forecast of 5% to 15% for the full year, despite current performance metrics indicating positive trends [22]. - **Gene Therapy Market Position**: Kanghong aims to leverage its gene therapy platform to address unmet medical needs and compete globally, with plans to expand into non-ophthalmic indications [16][18][30]. Additional Considerations - **Market Competition**: The evolving competition in the ophthalmology market, particularly regarding gene therapy and long-acting treatments, is a focal point for future strategies [25][27]. - **Business Development**: Ongoing discussions with over 20 potential partners for business development opportunities, influenced by the progress of competing products in the market [18]. This summary encapsulates the key points from the conference call, highlighting Kanghong Pharmaceutical's strategic initiatives, financial performance, and market outlook.

Core Viewpoint - AstraZeneca has announced a complete withdrawal from the CNS (Central Nervous System) field, terminating multiple pipeline projects, marking a significant strategic decision following its $80 billion revenue target announcement [1][2]. Group 1: AstraZeneca's Strategic Decision - The decision to exit the CNS field reflects the high difficulty of product development in this area and the pressure to achieve short-term KPIs, leading the company to focus on more certain high-revenue products like weight loss drugs and ADCs [2][4]. - The withdrawal indicates a significant loss of research investment and time, as the CNS field has seen mixed results in recent years, with other major companies like Amgen, Pfizer, and Sanofi also abandoning CNS projects [2][8]. Group 2: CNS Market Overview - The CNS market is considered the third-largest disease market, with a strong necessity for drug control and long medication cycles for conditions such as depression, schizophrenia, Parkinson's, and Alzheimer's [2][3]. - Despite recent setbacks, there have been notable breakthroughs in the CNS field, including advancements in Alzheimer's treatments and new mechanisms for schizophrenia drugs, indicating potential for future growth [7][12]. Group 3: Challenges in CNS Drug Development - CNS drug development faces significant challenges, including limited understanding of brain mechanisms, the blood-brain barrier, and subjective symptom assessment, leading to lower approval rates compared to non-CNS drugs [4][5]. - The slow iteration of drugs in the CNS field means that any successful product can enjoy a longer lifecycle with less competition, which has allowed smaller companies to establish themselves [5][12]. Group 4: Domestic CNS Players - The domestic CNS drug market in China is projected to grow from approximately $16.9 billion in 2022 to $31.1 billion by 2030, with a compound annual growth rate (CAGR) of nearly 8%, outpacing global growth [12][13]. - Local companies are increasingly focusing on innovative CNS drugs, with several firms transitioning from generics to original drug development, leveraging improved research infrastructure and market demand [13][14].