OBJECTIVE: To summarize the clinical characteristics of foot and ankle deformities combined with knee and lower limb deformities and evaluate the advantages, clinical outcomes, and considerations of QIN Sihe's surgical strategy for treating such complex deformities. METHODS: Between January 2022 and December 2024, 32 patients with foot and ankle deformities combined with knee and lower limb deformities were enrolled. The cohort included 23 males and 9 females, aged 10-67 years (mean, 41.1 years). The main etiologies included post-polio sequelae (20 cases) and congenital limb deformities (3 cases). Deformities were categorized as follows: equinovarus foot (12 cases), equinus foot (2 cases), equinovalgus foot (3 cases), equinus foot with swan-neck deformity (2 cases), calcaneus foot (5 cases), foot valgus (2 cases), knee flexion deformity (14 cases), genu recurvatum (4 cases), genu varum (3 cases), genu valgum (3 cases), lower limb shortening (3 cases), and lower limb external rotation (6 cases). QIN Sihe's surgical strategies included osteotomies, tendon releases, and tendon transfers for deformity correction, followed by external fixation for residual deformity adjustment and stabilization. Outcomes were assessed using QIN Sihe's Postoperative Evaluation Criteria for Lower Limb (Foot and Ankle) Deformity Correction and Functional Reconstruction. RESULTS: All patients were followed up 8-32 months (mean, 16.5 months). Complications included pin tract infection (1 case, 1 site), ankle pain (2 cases), delayed healing at the proximal tibial osteotomy site (1 case), and anterior talar dislocation (1 case). At last follow-up, insufficient correction of foot deformity was observed in 1 case; both knee and lower limb deformities were corrected, with only mild recurrence of knee flexion deformity in 1 case. The foot/ankle and knee joint function improved. Based on QIN Sihe's Postoperative Evaluation Criteria for Lower Limb (Foot and Ankle) Deformity Correction and Functional Reconstruction, outcomes were rated as excellent in 30 cases and good in 2 cases, with an excellent-good rate of 100%. CONCLUSION Foot and ankle deformities combined with knee and lower limb deformities are complex, QIN Sihe's surgical strategy can achieve satisfactory clinical outcomes for simultaneous correction.
Humans ; Male ; Female ; Adult ; Middle Aged ; Child ; Adolescent ; Aged ; Treatment Outcome ; Young Adult ; Plastic Surgery Procedures/methods* ; Lower Extremity Deformities, Congenital/surgery* ; Osteotomy/methods* ; Foot Deformities, Congenital/surgery* ; Ankle Joint/surgery* ; Knee Joint/surgery* ; Foot Deformities/surgery*

Kirsten rat sarcoma viral oncogene homolog (KRAS) protein inhibitors are a promising class of therapeutics, but research on molecules that effectively penetrate the blood-brain barrier (BBB) remains limited, which is crucial for treating central nervous system (CNS) malignancies. Although molecular generation models have recently advanced drug discovery, they often overlook the complexity of biological and chemical factors, leaving room for improvement. In this study, we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug efficacy and drug absorption properties. Our approach utilizes a variational autoencoder (VAE) generative model integrated with reinforcement learning for multi-objective optimization. This method specifically aims to enhance BBB permeability (BBBp) while maintaining high-affinity substructures of KRAS inhibitors. To support this, we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models. Additionally, we introduce two novel metrics, the knowledge-integrated reproduction score (KIRS) and the composite diversity score (CDS), to assess structural performance and biological relevance. Retrospective validation with KRAS inhibitors, AMG510 and MRTX849, demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications. This study provides a robust framework for accelerating the structural enhancement of lead compounds, advancing the drug development process across diverse targets.

Group C rotavirus（RVC）is one of the important etiological agents responsible for human rotavirus gastroenteritis（RVGE）. Although its overall detection rate has shown a declining trend in recent years，sporadic outbreaks continue to be reported，highlighting its potential public health threat. RVC infections predominantly occur in preschool children，adolescents，and adults，typically presenting with mild to moderate diarrhea. While most cases are sporadic，cluster outbreaks can also occur. At present，fundamental research on RVC remains limited，particularly regarding its transmission and pathogenesis. Nevertheless，emerging evidence suggests that interspecies transmission may represent a key route of human infection. This review provides a comprehensive overview of current research on RVC-associated gastroenteritis，with a particular focus on its virological characteristics，epidemiological patterns，clinical manifestations，and preventive and control strategies. It aims to offer a theoretical foundation and practical reference for future studies and public health interventions targeting RVC.

Objective To explore the efficacy and safety of interventional embolism in the treatment of hemoptysis from non-bronchial arterial system.Methods We retrospectively analyzed clinical data of 23 cases of non-bronchial artery system derived hemoptysis from February 2017 to November 2024.The hemorrhagic blood vessels were only the non-bronchial artery system in 6 cases,and from the non-bronchial artery system and bronchial arteries in 17 cases.Sources of non-bronchial artery systems included 14 intercostal arteries,5 thyrocervical trunk,5 subscapular arteries,4 internal thoracic arteries,3 external thoracic arteries,5 diaphragmatic arteries,1 renal artery,and 1 left gastric artery.All the patients were treated with interventional embolism.Recurrence rate was followed up and postoperative complications were recorded.Results The immediate hemostasis rate after surgery was 95.7%(22/23).In one case,hemoptysis was relapsed within 24 h after the operation due to omission of diaphragmatic artery,and hemoptysis did not recurred after the secondary embolization.After surgery,there was 1 case of abdominal discomfort,2 cases of fever,and 2 cases of chest pain.The symptoms disappeared after conservative treatment.After the operation,the follow-up was 4-36 months(median,30 months).A total of 20 patients did not re-develop hemoptysis,while 3 had relapsed hemoptysis at 4 months,4 months,and 36 months after operation,respectively,with a recurrence rate of 13.0%(3/23).No serious complications occurred.Conclusion Interventional embolism is effective in the treatment of non-bronchial hemoptysis,which is safe and feasible.

Objective To investigate the clinical efficacy of the"dynamic and static combination"approach in the treatment of Hepple Ⅰ-Ⅲ type osteochondral lesions of the talus(OLT),utilizing external ankle shaking,pulling,and poking manipulations in conjunction with ankle brace fixation.Methods A total of 82 patients diagnosed with OLT,who sought treatment at four hospitals between June 2022 and December 2023,were included in the study.Both the experimental and control groups received ankle immobilization using braces through-out the treatment period.The control group was administered Voltaren Emulgel topically twice daily(morning and evening),with each treatment course lasting 30 days,for a total of one course.The experimental group received additional therapeutic intervention involving shaking,pulling,and poking manipulations,conducted twice weekly,with the same duration and number of treatment courses as the control group.Follow-up assessments were scheduled at 2 weeks,4 weeks,and 2 months post-treatment.Outcome measures included the pain rating index(PRI),visual analogue scale(VAS)for pain intensity,current pain intensity(PPI),American Orthopaedic Foot & Ankle Society(AOFAS)ankle and hindfoot scores,proprioceptive function,and the size of OLT.Results During the longitudinal assessment conducted at 2-week,4-week,and follow-up intervals,the experimental group exhibited superior clinical outcomes compared to the control group,with statistically significant decreases in PRI,PPI,and AOFAS scores(all P＜0.05).VAS scores showed progressive improvement over time,with significant intergroup differences observed at both the 4-week and follow-up assessments(P＜0.05).Biomechanical analysis performed post-intervention indicated improved kinematic repositioning accuracy in the experimental group,as reflected by significantly reduced active-passive error angles(P＜0.05).Importantly,measurements of OLT area revealed notable therapeutic effects in the experimental group(P＜0.05),whereas no statistically significant changes were observed in the control group throughout the study period(all P＞0.05).Conclusions Under the guidance of the"dynamic and static combination"concept,the integration of shaking,pulling,and poking manipu-lation with conventional Western medicine-based conservative treatment for OLT demonstrates more pronounced advantages in alleviating pain,improving ankle joint function,restoring proprioception,facilitating lesion recovery,and enhancing overall quality of life.

Objective:To investigate the efficacy and safety of transcatheter arterial embolization(TAE)in the treatment of refractory bleeding caused by head,neck,and maxillofacial trauma.Methods:The clinical data of 26 patients with refractory bleeding caused by head,neck and maxillofacial trauma who were treated with TAE in The First Affiliated Hospital of Zhengzhou University and The Third People's Hospital of Henan Province were analyzed retrospectively,including 16 males and 10 females,with an average age of 57.96±15.52 years.All patients were treated with TAE because of the poor effect of medication,packing,and other measures and repeated bleeding.The clinical data,operation success rate,effective hemostasis rate,30-day clinical success rate,and postoperative complica-tions were analyzed.The patients were followed up for 3 to 6 months.Results:The operation success rate of TAE was 100%.The bleed-ing symptoms of all patients were effectively controlled,and the effective hemostasis rate was 100%.The hemoglobin level was in-creased from(96.21±12.42)g/L before operation to(111.38±7.70)g/L at 3 days after operation(P<0.001).After operation,3 pa-tients had slight swelling,pain,or skin color changes in the head,neck,and maxillofacial region,which were effectively relieved or dis-appeared after symptomatic treatment;2 patients died of severe traumatic brain injury and cerebral edema.No serious complications such as cerebral infarction occurred in any patients.There was no rebleeding in any patients within 3 to 6 months of post-discharge follow-up.Conclusion:TAE has definite curative effect and good safety for refractory bleeding caused by head,neck,and maxillofa-cial trauma,and has high clinical application value.

Perimenopausal anxiety and depression state fall under the categories of"visceral agitation"and"perimenopausal syndrome"in traditional Chinese medicine(TCM).Grounded in the theory of"Yang transforms qi,yin shapes form",this study posits that the pathogenesis of this condition is complex,often presenting with concurrent deficiency and excess syndromes,and is closely associated with yang deficiency-induced stagnation and qi stagnation leading to mental decline.The pathological mechanism is summarized as yang deficiency being the root and qi stagnation the manifestation.This article proposes a"yang-oriented treatment"approach for perimenopausal anxiety-depression disorders,employing a stepwise integrated acupuncture protocol termed"One Needling,Two Moxibustion,Three Consolidation":"One Needling"prioritizes regulating qi flow via acupuncture to soothe the liver and harmonize the spirit;"Two Moxibustion"utilizes refined moxibustion to warm yang,resolve stagnation,and activate yang circulation;"Three Consolidation"combines bloodletting therapy to remove stasis and regenerate tissues with intradermal needle embedding to stimulate yang and regulate visceral functions.This synergistic protocol aims to nourish the heart-mind,awaken the orifices of consciousness,alleviate perimenopausal anxiety and depressive symptoms,and consolidate therapeutic efficacy.

Kirsten rat sarcoma viral oncogene homolog(KRAS)protein inhibitors are a promising class of thera-peutics,but research on molecules that effectively penetrate the blood-brain barrier(BBB)remains limited,which is crucial for treating central nervous system(CNS)malignancies.Although molecular generation models have recently advanced drug discovery,they often overlook the complexity of bio-logical and chemical factors,leaving room for improvement.In this study,we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug effi-cacy and drug absorption properties.Our approach utilizes a variational autoencoder(VAE)generative model integrated with reinforcement learning for multi-objective optimization.This method specifically aims to enhance BBB permeability(BBBp)while maintaining high-affinity substructures of KRAS in-hibitors.To support this,we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models.Additionally,we introduce two novel metrics,the knowledge-integrated reproduction score(KIRS)and the composite diversity score(CDS),to assess structural performance and biological relevance.Retrospective validation with KRAS inhibitors,AMG510 and MRTX849,demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications.This study provides a robust framework for accelerating the structural enhancement of lead compounds,advancing the drug development process across diverse targets.

BACKGROUND:Patients with Alzheimer's disease have severe brain energy disorders.In recent years,brain energy rescue strategies based on ketone body intervention have attracted more and more attention in the treatment of Alzheimer's disease.OBJECTIVE:To investigate whether β-hydroxybutyric acid can improve energy dysfunction by improving mitochondrial bioenergy function in HT22 cells of mouse hippocampal neurons induced by amyloid-β protein 1-42 (Aβ1-42).METHODS:HT22 cells were divided into four groups:Control,β-hydroxybutyric acid,Aβ1-42,Aβ1-42+β-hydroxybutyric acid.Related detection kits were respectively used to detect HT22 cell survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,mitochondrial membrane potential,and reactive oxygen species levels.RESULTS AND CONCLUSION:Compared with the control group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly decreased (P<0.05),and the level of reactive oxygen species was significantly increased (P<0.05) in the Aβ1-42 group.Compared with the Aβ1-42 group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly increased (P<0.05),and the reactive oxygen species level was significantly decreased (P<0.05) in the Aβ1-42+β-hydroxybutyric acid group.These results showed that β-hydroxybutyric acid improved mitochondrial bioenergetic function and ultimately improved Aβ1-42-induced energy impairment and survival rate in HT22 cells.

Perimenopausal women are more susceptible to fire pathogen disturbances,often resulting in the restlessness of the mind owing to the deficiency and decline of the thoroughfare and conception vessels,as well as the insufficiency of the essence and blood of the viscera.CHENG Zhongling's theory of thief and child fire in Medical Insights proposes that thief fire primarily arises from exogenous pathogen invasion and improper diet,leading to syndromes such as food retention in the stomach or phlegm-fire stagnation.In contrast,child fire is generated endogenously,often owing to liver and kidney deficiency,resulting in an imbalance of water and fire and liver dysfunction,leading to excessive fire transformation.This theory provides a novel perspective for understanding the pathogenesis of perimenopausal insomnia.An in-depth exploration of the role of thief fire and child fire in perimenopausal insomnia is presented,along with a detailed discussion of corresponding treatment strategies.For the invasion of thief fire,therapeutic approaches include ascending and dispersing stagnant fire,clearing and moistening to remove interior heat,purging the heat accumulation to unblock the bowels,and subduing the fire and nourishing yin to eliminate depression.When child fire disturbs the spirit,treatment methods involve smoothing and relieving the liver qi to clear the stagnant heat,nourishing the true yin to restrain the yang,warming and nurturing the primordial qi and harmonizing the nutrient and defensive qi,and guiding and reducing the deficient heat to remove the floating fire.Clinical practice necessitates precise identification of thief and child fire,thorough investigation of exogenous pathogens and internal damage,and careful differentiation between deficiency and excess,as well as the superficial and internal aspects.Strict adherence to the treatment principle of"nourishing the child fire can drive out the thief fire,but driving out the thief fire should not harm the child fire"ensures a balanced approach.By harmonizing the yin and yang of the viscera and allowing the mind to be at ease,this strategy effectively alleviates perimenopausal insomnia.The application of these principles provides a practical and feasible theoretical foundation and practical guidance for the treatment of perimenopausal insomnia using traditional Chinese medicine.