Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

To report two cases of psychiatric symptoms associated with zonisamide, an antiepileptic drug, and raise clinical awareness of this potential adverse effect. Two male patients with epilepsy treated with zonisamide were retrospectively analyzed. Case 1 (25 years old) developed acute emotional and behavioral abnormalities (e.g., insomnia, aggression, incoherent speech) after switching from sodium valproate to zonisamide (200 mg/day). Case 2 (48 years old) had long-term zonisamide use (≥5 years) with persistent treatment-resistant psychotic symptoms (e.g., delusions, command hallucinations). Clinical courses, medication adjustments, and symptom responses were documented. In Case 1, psychiatric symptoms resolved after discontinuing zonisamide and switching to sodium valproate, with improved mood stability and reduced impulsivity. In Case 2, despite escalating antipsychotic medications (risperidone, clozapine), psychotic symptoms persisted, likely due to ongoing zonisamide use. Both cases highlighted zonisamide’s potential to exacerbate or induce psychiatric manifestations, possibly via mechanisms involving sodium/calcium channel inhibition and neurotransmitter dysregulation (e.g., dopamine, serotonin). Zonisamide can cause or worsen psychiatric symptoms, particularly in vulnerable individuals. Clinicians should monitor for mental health changes during zonisamide treatment and consider drug discontinuation or substitution with alternative antiepileptics (e.g., sodium valproate) if psychiatric adverse effects emerge. Awareness of this association is crucial to avoid misdiagnosis and optimize epilepsy management.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

ObjectiveTo elucidate the efficacy connotation of Shudi Qiangjin pills （SQP） against liver and kidney deficiency in steroid-induced osteonecrosis of femoral head （SONFH） from the perspective of the "disease-syndrome-formula" association and to clarify the underlying mechanisms based on in vivo and in vitro experiment validation. MethodsThe chemical components and the corresponding putative targets of SQP were collected from the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0， the Encyclopedia of Traditional Chinese Medicine （ETCM） v2.0， and HERB databases. The SONFH-related genes were identified based on the differential expression profiles of peripheral blood of patients with SONFH compared to the healthy volunteers， and the disease phenotype-related targets were collected from the TCMIP v2.0 database. Then， the interaction network of "SONFH-related genes and candidate targets of SQP" was constructed based on "gene-gene interaction information"， and the major network targets were screened by calculating the topological characteristic values of the network followed by the functional mining according to the Kyoto Encyclopedia of Genes and Genomes （KEGG） database and the SoFDA database. After that， the SONFH rat model was prepared by lipopolysaccharide combined with methylprednisolone injection， and 2.5， 5， 7.5 g·kg^-1 SQP （once per day， equivalent to 1， 2， and 3 times the clinical equivalent dose， respectively） or 7.3×10^-3 g·kg^-1 of alendronate sodium （ALS， once per week， equivalent to the clinical equivalent dose） was given for 8 weeks. The effect characteristics of SQP and ALS in the treatment of SONFH were evaluated by micro-computed tomography scanning， hematoxylin and eosin staining， alkaline phosphatase （ALP） staining， immunohistochemical staining， enzyme-linked immunosorbent assay， and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling（TUNEL）staining， and a comparative efficacy analysis was conducted with ALS. In addition， SONFH cell models were prepared by dexamethasone stimulation of osteoblasts， and the intervention was carried out with the medicated serum of SQP at the aforementioned three doses. Cell counting kit-8， ALP staining， ALP activity assay， alizarin red staining， and flow cytometry were employed to investigate the regulatory effect of SQP on osteoblasts. The expression levels of osteogenesis-related proteins and key factors of the target signaling axis were detected by quantitative real-time polymerase chain reaction and Western blot. ResultsThe network analysis results demonstrated that the candidate targets of SQP primarily exerted their therapeutic effects through key signaling pathways， including phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt）， lipid metabolism and atherosclerosis， prolactin， chemokines， and neurotrophic factors pathways. These pathways were significantly involved in critical biological processes such as muscle and bone metabolism and the regulation of the "neuro-endocrine-immune" network， thereby addressing both modern medical symptoms （e.g.， delayed skeletal maturation and recurrent fractures） and traditional Chinese medicine （TCM） symptoms （e.g.， fatigue， aversion to cold， cold limbs， and pain in the limbs and joints in patients with SONFH characterized by liver and kidney deficiency syndrome. Among these pathways， the PI3K/Akt signaling pathway exhibited the highest degree of enrichment. The in vivo experimental results demonstrated that starting from the 4^th week after modeling， the modeling group exhibited a significant reduction in body weight compared to the control group （P<0.05）. After six weeks of treatment， all dosage groups of SQP showed significantly higher body weights compared to the model group （P<0.01）. Compared with the normal group， the model group exhibited significant decreases in bone mineral density （BMD）， bone volume fraction （BV/TV）， trabecular number （Tb.N）， osteocalcin （OCN）， alkaline phosphatase （ALP） levels in femoral head tissue， and serum bone-specific alkaline phosphatase （BALP） （P<0.01）， along with significant increases in trabecular separation （Tb.Sp）， empty lacunae rate in tissue， and apoptosis rate （P<0.01）. In comparison to the model group， the SQP intervention groups showed significant improvements in BMD， BV/TV and Tb.N （P<0.01）， significant reductions in Tb.Sp， empty lacunae rate and apoptosis rate （P<0.05）， and significant increases in protein levels of OCN and ALP as well as BALP content （P<0.05）. The in vitro experimental results revealed that all dosage groups of SQP medicated serum showed no toxic effects on osteoblast. Compared with the normal group， the model group displayed significant suppression of osteoblast proliferation activity， ALP activity， and calcified nodule formation rate （P<0.01）， significant decreases in mRNA transcription levels of OCN and Runt-related transcription factor 2 （RUNX2） （P<0.01）， significant reductions in protein content of osteopontin （OPN）， typeⅠ collagen （ColⅠ）A1， B-cell lymphoma-2 （Bcl-2）， PI3K， and phosphorylated （p）-Akt （P<0.01）， and a significant increase in apoptosis rate （P<0.01）. Compared with the model group， the SQP medicated serum intervention groups exhibited significant increases in proliferation activity， ALP activity， calcified nodule formation rate， mRNA transcription levels of OCN and RUNX2， and protein content of OPN， ColⅠA1， Bcl-2， PI3K， and p-Akt （P<0.05）， along with a significant decrease in apoptosis rate （P<0.01）. ConclusionSQP can effectively reduce the disease severity of SONFH with liver and kidney deficiency syndrome and improve bone microstructure， with the therapeutic effects exhibiting a dose-dependent manner. The mechanism may be related to its regulation of key processes such as muscle and bone metabolism and the correction of imbalances in the "neuro-endocrine-immune" network， thereby promoting osteoblast differentiation and inhibiting osteoblast apoptosis. The PI3K/Akt signaling axis is likely one of the key pathways through which this formula exerts its effects.

Objective To understand mosquito density, species composition, and seasonal variations around the Beijing Capital International Airport(BCIA)and provide scientific evidence for mosquito-borne disease prevention and control. Methods Meteorological data were collected from 2016 to 2022, and mosquito density was monitored at seven surveillance sites around the BCIA from May to October each year using CO2-baited mosquito traps to analyze the relationship between mosquito density and meteorological factors. Results In total,68 518 female mosquitoes were captured, with a mosquito density of 10.20 per light · hour. The dominant species was Culex pipiens pallens(73.90%), followed by Aedes albopictus(9.71%)and Ae. vexans(9.29%);the mosquito density was highest in 2016(14.8 per light·hour)and lowest in 2022(4.46 per light·hour). Significant statistical differences were observed in mosquito density among different species(F=18.118, P<0.05). The density of Cx. pipiens pallens and other mosquito species showed a mutually exclusive trend; the peak of mosquito density varied based on years and habitats, with significant statistical differences in mosquito density among different habitats(F=8.504, P<0.05). The highest mosquito density was observed near the Wenyu River(21.50 per light·hour), whereas the lowest was recorded at the BCIA construction site(2.44 per light· hour). The monthly average temperature(r=0.595), monthly average highest temperature(r=0.575), and monthly average lowest temperature(r=0.624)showed moderate positive correlations, whereas the monthly average air pressure(r=-0.484)showed a moderate negative correlation. The monthly average minimum temperature was included in the regression model(F=25.575, P<0.000), and the equation Y=1.029X4-8.181 was used. The monthly average air pressure 2 months prior(b=-2.418, β=-1.619, P<0.05)and the monthly average relative humidity(b=-0.739, β=-1.201, P<0.05)significantly negatively predicted the mosquito density. Notably, the regression equation used was y=2526.170+(-2.418)X9+(-0.739)X13. The exposure-response analysis revealed that the density of mosquitoes was not linearly related to the average monthly air pressure, rainfall, and duration of sunshine. Conclusions The dominant mosquito species around the BCIA was Cx. pipiens pallens, Ae. albopictus, and Ae. vexans. During the control of Cx. pipiens pallens, the impact on other mosquito species must also be considered. Environmental management, breeding sites, and scientific use of pesticides should be prioritized based on the activity periods of mosquitoes. Further studies on mosquitoes and meteorological factors should be conducted to provide references and novel avenues for mosquito control.

OBJECTIVE To provide scientific reference for perfecting the record-filing management policy of traditional Chinese medicine preparations formulated via traditional processes for medical applications （hereinafter referred to as “TCM preparations”） in medical institutions， and further promote the sound development of the research and record-filing work of such preparations. METHODS A literature review combined with cross-sectional research was carried out. We collected policy documents and preparation information related to the record-filing of TCM preparations issued by national and provincial drug administration authorities on official websites during 2018-2025. A comparative analysis was conducted on the implementation and revision of core policy documents for the registration management of TCM preparations across provinces， the scope of record-filing dosage forms， conditions for rejection of record-filing， and exemptions for registration materials. Statistical analysis on the quantity and dosage forms of record-filing preparations in each province was conducted by means of data induction and trend chart plotting， and targeted suggestions were put forward to optimize the management pathway of record-filing. RESULTS CONCLUSIONS There was obvious heterogeneity in record-filing policies among provinces. Twelve provinces refined the applicable dosage forms for record-filing， fifteen provinces supplemented conditions for rejection of record-filing （16 items in total）， and nine provinces expanded the scope of material exemptions. The number of recorded preparations presented a striking regional imbalance：Qinghai had the largest quantity of 4 269 varieties， while Hainan only had 14 varieties， with a gap of more than 300 times. The recorded preparations were mainly traditional dosage forms including pills （6 928 varieties） and powders （4 360 varieties）. Only 12 provinces formulated the provincial catalog for TCM preparations allocation. In most regions， preparation circulation was only permitted within medical consortia， leading to a low transformation rate of scientific and technological achievements of preparations. It is recommended to optimize the record-filing management pathway from three aspects： strengthening policy standardization while maintaining flexibility， streamlining record-filing procedures and documentary requirements， and reinforcing technical support and achievement transformation. These measures can reduce regional policy differences， improve work efficiency of record-filing， and advance the standardized development and clinical value transformation of hospital-made TCM preparations.

OBJECTIVE To provide scientific reference for perfecting the record-filing management policy of traditional Chinese medicine preparations formulated via traditional processes for medical applications （hereinafter referred to as “TCM preparations”） in medical institutions， and further promote the sound development of the research and record-filing work of such preparations. METHODS A literature review combined with cross-sectional research was carried out. We collected policy documents and preparation information related to the record-filing of TCM preparations issued by national and provincial drug administration authorities on official websites during 2018-2025. A comparative analysis was conducted on the implementation and revision of core policy documents for the registration management of TCM preparations across provinces， the scope of record-filing dosage forms， conditions for rejection of record-filing， and exemptions for registration materials. Statistical analysis on the quantity and dosage forms of record-filing preparations in each province was conducted by means of data induction and trend chart plotting， and targeted suggestions were put forward to optimize the management pathway of record-filing. RESULTS CONCLUSIONS There was obvious heterogeneity in record-filing policies among provinces. Twelve provinces refined the applicable dosage forms for record-filing， fifteen provinces supplemented conditions for rejection of record-filing （16 items in total）， and nine provinces expanded the scope of material exemptions. The number of recorded preparations presented a striking regional imbalance：Qinghai had the largest quantity of 4 269 varieties， while Hainan only had 14 varieties， with a gap of more than 300 times. The recorded preparations were mainly traditional dosage forms including pills （6 928 varieties） and powders （4 360 varieties）. Only 12 provinces formulated the provincial catalog for TCM preparations allocation. In most regions， preparation circulation was only permitted within medical consortia， leading to a low transformation rate of scientific and technological achievements of preparations. It is recommended to optimize the record-filing management pathway from three aspects： strengthening policy standardization while maintaining flexibility， streamlining record-filing procedures and documentary requirements， and reinforcing technical support and achievement transformation. These measures can reduce regional policy differences， improve work efficiency of record-filing， and advance the standardized development and clinical value transformation of hospital-made TCM preparations.

Sichuan Province is a hilly schistosomiasis-endemic province in China with the highest endemicity and largest coverage. During the period of more than 70 years of integrated control, there are five distinct phases of schistosomiasis control in Sichuan Province, including baseline investigation, Oncomelania hupensis snail control, chemotherapy for both humans and livestock, management of source of Schistosoma japonicum infections, and sustained control and intensified surveillance and early warning, and a package of key interventions are implemented, including environmental modification, snail control with chemical treatment, large-scale chemotherapy for humans and livestock, management of source of S. japonicum infections, intensified integrated control, establishment of an early warning and surveillance system. As a result, schistosomiasis has been eliminated across all 63 disease-endemic counties (cities, districts) in Sichuan Province by June 2025. Government-led multi-sectoral collaborations, science and technology-supported precision control strategies, and a sustainable control model tailored to the ecological and socio-economic conditions in endemic regions are essential to achieving the target of schistosomiasis elimination in Sichuan Province.

In recent years, remarkable advances have been made in lung transplantation regarding donor evaluation, perioperative support, and immune regulation, laying a foundation for improving the long-term survival of recipients. The rational application of extended criteria donor lungs and the popularization of ex vivo lung perfusion technology have enhanced the utilization efficiency and safety of marginal donor lungs. Refined assessment of risk factors such as donors’ smoking history and infectious status has reduced the incidence of primary graft dysfunction and postoperative infection. In terms of recipient management, individualized assessment systems have been gradually optimized. The standardized application of intraoperative extracorporeal membrane oxygenation and the development of minimally invasive surgical techniques have effectively alleviated perioperative injuries. The optimization of postoperative immunosuppressive regimens and advances in rejection monitoring technologies have further improved the long-term survival of grafts. Nevertheless, chronic graft dysfunction and recurrent or refractory infections remain the major bottlenecks restricting long-term prognosis. Future research should focus on expanding donor sources, improving the repair quality of marginal donor lungs, promoting precise immunosuppression and anti-infection strategies, and comprehensively enhancing the long-term survival rate and quality of life of lung transplant recipients.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.