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.

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.

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.

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.

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Objective:To explore the diagnosis and treatment of Sjogren′s syndrome in military pilots and the principles of aeromedical assessment.Methods:The conclusions of clinical diagnosis and treatment and aeromedical assessment were analyzed by reporting the clinical data of a pilot with Sjogren′s syndrome and reviewing the relevant literatures.Results:This pilot with Sjogren′s syndrome was admitted to the Medical Evaluation Department of Air Force Medical Center because of the physical examination for transformation, and there was no complaint of discomfort. Assay anti-nuclear antibody spectrum: anti-Ro-52 was positive. When the medical history was questioned, he complained of occasional dry eyes, so he underwent dry eye examination. The mean tear film rupture time was 10.24 s in the right eye and 7.38 s in the left eye. Lacrimal river height was 0.22 mm in the right eye and 0.15 mm in the left eye. Xerophthalmia was diagnosed. Salivary gland dynamic imaging examination indicated that the uptake and excretion functions of bilateral parotid glands were significantly reduced, which was consistent with Sjogren′s syndrome and confirmed as Sjogren′s syndrome. Through a comprehensive systematic examination, no damage to other organs was detected. Because of the current symptoms were mild and had no obvious impact on flight, the pilot was qualified for flight. Symptomatic treatment and regular hospital check-ups applied to monitor the changes of the disease.Conclusions:The early symptoms of Sjogren′s syndrome are mild and easy to be missed, so it is necessary to improve the awareness of the disease. Aeromedical assessment should be carried out according to the severity of the disease, the therapeutic effect, the aircraft types, the post of flight and the flight experience.

Objective:To investigate the diagnosis and treatment of pilots with patent foramen ovale resulting in encephalomalacia foci and discuss the aeromedical assessment principles.Methods:The clinical manifestations, cranial MRI, cardiac ultrasound and transesophageal echocardiography of a pilot with patent foramen ovale and encephalomalacia foci were retrospectively analyzed, and the relevant literatures were reviewed.Results:The patient was a male fighter pilot, 28 years old, without clinical symptoms and complaints of discomfort. A left temporal pole arachnoid cyst (2.18 cm×1.11 cm) and a left frontal brain softening foci (1.80 cm×3.50 cm×3.30 cm) were detected by cranial MRI during physical examination, and patent foramen ovale was detected by transesophageal echocardiography and foam test after admission. The oval foramen was occluded under local anesthesia. The patient was well-recovered after surgery and without discomfort. The cardiac ultrasound recheck showed normal myocardial echoes in the septum and left ventricular wall, no abnormalities in wall thickness and motion amplitude, and coordinated ventricular wall motion. Strong echogenicity of the blocker was seen in the middle of the atrial septum, and the position of the blocker was normal. The aeromedical assessment conclusion of the patient was waiver to flight.Conclusions:The patent foramen ovale should be screened when pilot is diagnosed as encephalomalacia foci or cerebral infarction. The regular reexamination and follow-up should be conducted for the transcatheter occlusion of patent foramen ovale. Pilots could be waivered when they have no clinical symptoms and signs, no arrhythmias and at proper position in dynamic electrocardiogram and submaximal treadmill exercise test, no residual shunt, valve regurgitation, or occluder erosion in imaging examination, and normal cardiac function, reserve function, and regulatory function, normal pressurized breathing and without arrhythmias in centrifuge run, and the grounding observation period is not less than 6 months.

Objective:To explore the diagnosis and treatment of Sjogren′s syndrome in military pilots and the principles of aeromedical assessment.Methods:The conclusions of clinical diagnosis and treatment and aeromedical assessment were analyzed by reporting the clinical data of a pilot with Sjogren′s syndrome and reviewing the relevant literatures.Results:This pilot with Sjogren′s syndrome was admitted to the Medical Evaluation Department of Air Force Medical Center because of the physical examination for transformation, and there was no complaint of discomfort. Assay anti-nuclear antibody spectrum: anti-Ro-52 was positive. When the medical history was questioned, he complained of occasional dry eyes, so he underwent dry eye examination. The mean tear film rupture time was 10.24 s in the right eye and 7.38 s in the left eye. Lacrimal river height was 0.22 mm in the right eye and 0.15 mm in the left eye. Xerophthalmia was diagnosed. Salivary gland dynamic imaging examination indicated that the uptake and excretion functions of bilateral parotid glands were significantly reduced, which was consistent with Sjogren′s syndrome and confirmed as Sjogren′s syndrome. Through a comprehensive systematic examination, no damage to other organs was detected. Because of the current symptoms were mild and had no obvious impact on flight, the pilot was qualified for flight. Symptomatic treatment and regular hospital check-ups applied to monitor the changes of the disease.Conclusions:The early symptoms of Sjogren′s syndrome are mild and easy to be missed, so it is necessary to improve the awareness of the disease. Aeromedical assessment should be carried out according to the severity of the disease, the therapeutic effect, the aircraft types, the post of flight and the flight experience.

Objective:To investigate the diagnosis and treatment of pilots with patent foramen ovale resulting in encephalomalacia foci and discuss the aeromedical assessment principles.Methods:The clinical manifestations, cranial MRI, cardiac ultrasound and transesophageal echocardiography of a pilot with patent foramen ovale and encephalomalacia foci were retrospectively analyzed, and the relevant literatures were reviewed.Results:The patient was a male fighter pilot, 28 years old, without clinical symptoms and complaints of discomfort. A left temporal pole arachnoid cyst (2.18 cm×1.11 cm) and a left frontal brain softening foci (1.80 cm×3.50 cm×3.30 cm) were detected by cranial MRI during physical examination, and patent foramen ovale was detected by transesophageal echocardiography and foam test after admission. The oval foramen was occluded under local anesthesia. The patient was well-recovered after surgery and without discomfort. The cardiac ultrasound recheck showed normal myocardial echoes in the septum and left ventricular wall, no abnormalities in wall thickness and motion amplitude, and coordinated ventricular wall motion. Strong echogenicity of the blocker was seen in the middle of the atrial septum, and the position of the blocker was normal. The aeromedical assessment conclusion of the patient was waiver to flight.Conclusions:The patent foramen ovale should be screened when pilot is diagnosed as encephalomalacia foci or cerebral infarction. The regular reexamination and follow-up should be conducted for the transcatheter occlusion of patent foramen ovale. Pilots could be waivered when they have no clinical symptoms and signs, no arrhythmias and at proper position in dynamic electrocardiogram and submaximal treadmill exercise test, no residual shunt, valve regurgitation, or occluder erosion in imaging examination, and normal cardiac function, reserve function, and regulatory function, normal pressurized breathing and without arrhythmias in centrifuge run, and the grounding observation period is not less than 6 months.