Mitochondrial quality control （MQC） homeostasis serves as a fundamental mechanism in maintaining the mitochondrial structure and function. Dysregulation of MQC contributes to the progression of acute ischemic stroke （AIS） through multiple pathways including disturbances in energy metabolism， increased oxidative stress， and imbalances in mitochondrial fusion and fission. Drawing upon the traditional Chinese medicine （TCM） theory of the kidney governing Yin and Yang， this study innovatively proposes an integrative model of "Yin-Yang dynamic balance-MQC homeostasis" to elucidate the underlying pathophysiological mechanisms. Specifically， kidney Yang deficiency and decline result in reduced driving force， thereby inhibiting mitochondrial fusion. This leads to decreased efficiency of oxidative phosphorylation and impaired adenosine triphosphate （ATP） production. Conversely， when kidney Yin is dysfunctional and excessive phlegm-blood stasis accumulates， mitochondrial fission becomes hyperactive， causing rapid accumulation of reactive oxygen species （ROS） and intensified oxidative stress. The interplay between these two pathological states culminates in the central TCM pathogenesis—Yin-Yang imbalance and disordered Qi and blood-of AIS. To address this pathogenesis， a therapeutic strategy is proposed： tonifying the kidney as the primary intervention to restore MQC homeostasis， supplemented by resolving phlegm and removing blood stasis to interrupt the deleterious cycle of cerebral vascular damage. This work integrates the holistic perspective of TCM with contemporary molecular insights， offering precise intervention targets along the "kidney-mitochondria axis" for the prevention and treatment of AIS， while establishing a novel integrative paradigm for stroke management that bridges traditional and modern medicine. Future research should focus on elucidating the molecular mechanisms through which TCM regulates MQC in AIS and integrating classical TCM theories with evidence-based medicine to facilitate the translation of theoretical insights into clinical applications.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a patient with Progressive pseudorheumatoid dysplasia (PPRD) due to compound heterozygous variants of CCN6 gene. METHODS: A patient who was admitted to Qilu Hospital of Shandong University due to "bilateral finger joint deformity, bilateral hip and knee joint movement limitation for 19 years" was selected as the study subject. Clinical data of the patient were retrospectively collected. Peripheral blood samples were collected from the patient and her parents and subjected to whole exome sequencing (WES). Long-read sequencing (LRS) and Sanger sequencing were used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was classified. This study was approved by the Medical Ethics Committee of Qilu Hospital of Shandong University (Ethics No.: KYLL-202502 061). RESULTS: The patient, a 23-year-old female, presented with progressive polyarticular deformity, limited movement and abnormal growth and development since childhood. She was initially misdiagnosed as Ankylosing spondylitis and had poor response to sulphasalazine and etoricoxib treatment. WES revealed that she has harbored two heterozygous variants of the CCN6 gene (NM_198239.2), namely c.348C>A and c.676G>C. LRS confirmed that the two variants are located on two homologous chromosomes and constitute compound heterozygous variants. Based on the ACMG guidelines, both variants were rated as pathogenic (PVS1+PM2_Supporting+PM3; PM1+PM2_Supporting+PM3_Supporting+PM5+PP3_Strong). The c.676G>C variant has not been recorded by the HGMD and ClinVar databases. CONCLUSION The c.348C>A and c.676G>C compound heterozygous variants of the CCN6 gene probably underlay the pathogenesis of PPRD in this patient. Above finding has enriched the mutational spectrum of PPRD and provided a basis for the clinical diagnosis and genetic counseling.
Humans ; Female ; CCN Intercellular Signaling Proteins/genetics* ; Phenotype ; Heterozygote ; Young Adult ; Mutation ; Exome Sequencing ; Joint Diseases/congenital*

To explore the ultrasound characteristics of accessory cavitated uterine malformation (ACUM) and the causes of misdiagnosis, in order to better understand the disease and improve the diagnostic ability of radiologists.

Objective To investigate the protective and treatment role of ulinastatin(UTI)on con-trast-induced acute kidney injury(CIAKI)in the elderly with coronary heart disease(CHD)and chronic kidney diseases(CKD).Methods A total of 321 elderly CHD inpatients complicated with CKD undergoing coronary angiography admitted in the First Medical Center of Chinese PLA Gen-eral Hospital from November 2021 to November 2022 were enrolled consecutively and then divid-ed into UTI group(n=161)and hydration group(n=160).Their cardiac and renal function pa-rameters were collected and analyzed before and 2 d after intervention.The changes in above pa-rameters and incidence of CIAK were observed and compared between the two groups.Results In 2 d after intervention,the UTI group had significantly lower Scr,urea,CysC,homocysteine and NT-proBNP,but higher eGFR than the hydration group(P＜0.01).There were 62 patients(62/321,19.3％)developing CIAKI,including 17 from the UTI group and 45 from the hydration group,and statistical difference was observed in the incidence(10.6％vs 28.1％,P＜0.01).For the patients with comorbidities of hypertension,diabetes,hyperlipidemia and hyperuricemia,the incidence of CIAKI was obviously lower in the UTI group than the hydration group(P＜0.01).Multivariate logistic regression analysis showed that UTI was an independent protective factor for occurrence of CIAKI(OR=0.348,95％CI:0.180-0.673,P=0.001).Conclusion UTI can im-prove renal function and reduce the risk of CIAKI in elderly CHD patients with CKD.

ObjectiveTo study the effect and mechanism of Linggui Zhugantang in treating chronic bronchitis （CB） induced by exposure to cigarette smoke combined with tracheal instillation of lipopolysaccharide （LPS）. MethodSixty SPF-grade SD rats were randomly divided into normal， model， dexamethasone （1 mg·kg^-1）， and high-， medium-， and low-dose （30.06， 15.03， 7.515 g·kg^-1， respectively） Linggui Zhugantang groups by the body weight stratification method， with 10 rats in each group. Each group was administrated with 200 μL LPS （1 g·L^-1） by tracheal instillation on days 1 and 14， respectively， while the normal group was administrated with an equal volume of normal saline. Except the normal group， the other groups were exposed to cigarette smoke on days 2-13 and 15-30 （10 cigarettes/time/30 min， twice/day） for the modeling of CB. The rats were administrated with corresponding drugs by gavage for 30 consecutive days from day 2 of modeling， and the mental status， behavior， and body weights of the rats were observed and measured. The wet/dry mass ratio （W/D） of the left lung was measured 30 days after modeling. Hematoxylin-eosin staining was employed to observe the pathological changes in the lung and bronchial tissues. The bronchial mucus secretion and goblet cell proliferation were observed by Alcian blue-periodic acid Schiff （AB-PAS） staining. The levels of mucin 5AC （MUC5AC）， interleukin （IL）-13， IL-6， and tumor necrosis factor （TNF）-α in the serum were determined by enzyme-linked immunosorbent assay. The expression of phospholipase A2 （PLA2）， transient receptor potential vanilloid receptor 1 （TRPV1）， and transient receptor potential ankyrin 1 （TRPA1） in the lung tissue was quantitatively analyzed by immunohistochemistry and Western blot. ResultCompared with the normal group， the model group showcased abnormal mental status and behaviors， bloody secretion in the nose and mouth， the mortality rate of 40%， decreased body weight， severe lung bronchial structure damage， a large number of inflammatory mediators and inflammatory cell infiltration in the tube wall， hyperemia， edema， and fibroplasia， massive proliferation of goblet cells， excessive secretion and accumulation of mucus， stenosis and deformation of the lumen， and aggravation of pulmonary edema （P<0.01）. In addition， the model group had higher levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and higher expression of PLA2 in the lung tissue than the normal group （P<0.01）. Compared with the model group， the medication groups showed normal mental status and behaviors， reduced mortality rate， stable weight gain， reduced lung and bronchial injuries， decreased goblet cell proliferation and mucus secretion， and alleviated pulmonary edema （P<0.01）. Furthermore， Linggui Zhugantang lowered the levels of MUC5AC， IL-13， IL-6， and TNF-α in the serum and down-regulated the protein levels of PLA2， TRPV1， and TRPA1 in the lung tissue （P<0.01）. ConclusionLinggui Zhugantang can reduce the pulmonary inflammation and airway mucus hypersecretion in the rat model of chronic bronchitis. It may exert the effects of reducing inflammation and resolving phlegm by regulating the PLA2-TRPV1/TRPA1 pathway.

Objective To explore the possibility of rhabdomyolysis and related organ damage in new recruits training in high temperature and high humidity environment by comparing the effects of different training environments on the laboratory indicators and electrocardiogram.Methods A total of 250 new recruits from a unit in Beijing and another 250 ones from a unit in Hainan were recruited and assigned into conventional environment group and high temperature and high humidity environment group,respectively.All of them were male,with an average age of 21.36±2.59 years.Before and in 4 weeks after training in the same subjects,their general information,blood and urine indicators,and electrocardiogram were collected.All data were statistically analyzed.Results The incidences of inflammatory reaction,myocardial injury,muscle injury,liver injury,and kidney injury were 45.76％,3.39％,12.71％,25.42％,and 12.71％,respectively,in the high temperature and high humidity environment group,which were all significantly higher than those in the conventional environment group(P＜0.05).The former group had an incidence rate of 6.78％,5.93％,8.47％,6.78％,and 2.54％,respectively,in sinus bradycardia,atrial premature beats,unspecific ST-T changes,left ventricular hypertension and short PR interval,and all of the rates were higher than those of the conventional environment group(P＜0.05).Conclusion The incidences of inflammatory reaction,myocardial injury,muscle injury,liver injury,kidney injury,and ECG abnormalities are more common in new recruits after military training in high temperature and high humidity environment.

Within traditional teaching models,students frequently assume a passive role in acquiring knowledge,potentially resulting in diminished motivation and limited engagement,particularly within the realm of Medical Immunology education.The inte-gration of role-playing,informed by constructivist learning theory,situated learning theory,and multiple intelligences theory,has demonstrated encouraging outcomes within clinical medical education settings.However,the extent to which this approach has been explored within the context of Immunology instruction remains insufficiently examined.This study investigates the utilization of role-playing as a pedagogical approach in Medical Immunology education,wherein students are assigned specific scenarios to simulate the functions of various immune components.The primary objective is to augment interactivity and the overall appeal of the learning pro-cess.Efficacy of this instructional method was evaluated through in-class quizzes,surveys,and performance analysis.The findings demonstrate that role-playing substantially enhances student engagement,comprehension,knowledge retention,and examination per-formance.In practical application,the integration of role-playing with ideological and political elements has the potential to enhance learning outcomes and foster students'enthusiasm for engaging in cutting-edge literature and immunological research.This approach also necessitates greater proficiency in teachers'professional competencies and organizational skills,as well as increased allocation of class time and spatial resources.Future research should investigate the applicability of role-playing across various educational levels and examine its potential integration with classroom ideological and political education.

Objective By comparing the changes in cerebral blood flow,neuronal morphology in brain tissue,and the levels of serum oxidation and inflammatory factors in models of cerebral hypoperfusion,three experimental rat models were assessed for their suitability as subjects of studies on the mechanisms and therapeutic drugs of cerebrovascular diseases and neurodegenerative diseases.Methods A total of 88 male SD rats were randomly divided into a sham operation group(n=16),classic bilateral common carotid artery occlusion group(classic 2-VO group,n=24),modified 2-VO group(n=24),and intraluminal thread technique group(n=24).Bilateral common carotid artery ligation was performed on the classic 2-VO group,while blood was drawn from the common carotid artery before ligation in the modified 2-VO group(1 mL/100 g).Middle cerebral artery occlusion was performed on the intraluminal thread technique group.In the sham operation groups of the first two models,the common carotid artery was separated but not ligated,while the proximal end of the common carotid artery and the external carotid artery were ligated;in addition,the bolt thread was not inserted in the sham group of the intraluminal thread technique group.Cerebral blood flow,infarct volume,serum inflammatory factor levels,hematoxylin and eosin-stained morphology,and ultrastructure of the hippocampal tissue were assessed at 1,3,and 7 days after the operations.Results Laser speckle interferometry showed a decrease in cerebral blood flow of the modified 2-VO group that was more obvious than that of the other two groups.On day 7,only the modified 2-VO group still had significant differences in cerebral blood flow compared with the sham group,and it remained in a state of hypoperfusion(cerebral blood flow decreased by 30％compared with that before the operation).TTC staining showed that infarcts in the striata of the three groups gradually increased with time after the operation;4 rats(about 26.7％)in the modified 2-VO group and 10 rats(about 66.7％)in the intraluminal thread technique group had infarcts in both the cortex and striatum.ELISA showed that the levels of inflammatory factors,such as TNF-α,IL-1 β,and hs-CRP,in the three groups were increased after the operations,and levels of the pro-oxidation factor ROS were also increased.In contrast,levels of the antioxidant factor SOD decreased.On postoperative day 7,there was no significant difference in the hs-CRP of the classic 2-VO and intraluminal thread technique groups compared with that of the sham group.However,the modified 2-VO group still exhibited significant differences in all the above indicators compared with the sham group.Hematoxylin and eosin staining showed that the modified 2-VO group had more severe damage to the hippocampal CA1 and CA3 regions compared with the other groups.Transmission electron microscopy demonstrated that the modified 2-VO group showed more severe damage to the mitochondrial and endoplasmic reticulum in the hippocampal region compared with the other groups.Conclusions A cerebral hypoperfusion model was successfully established.Compared with the classic 2-VO and intraluminal thread techniques,the modified 2-VO method can induce more complete cerebral hypoperfusion and more severe neural damage within the same time frame,resembling the pathological state of human cerebral hypoperfusion more closely.

Purpose To explore the application of contrast-enhanced ultrasound in evaluating the local muscle microcirculation before and after acupuncture at Zusanli point in normal people.Materials and Methods A total of 72 healthy volunteers who visited the Department of Ultrasound,the Second Affiliated Hospital of Fujian Medical University from September 2018 to May 2020 were prospectively collected,all subjects performed ultrasound contrast before acupuncture,acupuncture with strongest deqi,and two hours after acupuncture to observe the blood flow perfusion of the microvessels in the tibialis anterior muscle.The pre-selected areas of interest the small arteries,muscle tissues and venules in the middle were analyzed to obtain the time-intensity curve and contrast transit time(CTTs)perfusion parameters.Needle sensation was evaluated using objective scoring criteria for acupuncture combined with moxibustion recipients.Gastrin,plasma gastrin,cholecystokinin,and secretin were measured in all subjects before acupuncture,when acupuncture had the strongest deqi,and two hours after acupuncture.Results ①CTTs of arterial-muscle,muscle-venous and arterial-venous of the tibialis anterior muscle at acupuncture with strongest deqi were significantly shorter than those at before acupuncture and two hours after acupuncture(all P<0.001),and there was no significant difference in CTTs before and after acupuncture and moxibustion(P>0.05);②when acupuncture deqi was strongest,serum gastrin,plasma prokinetics,cholecystokinin,and secretin were significantly increased compared with those before acupuncture and two hours after acupuncture,with statistically significant difference(all P<0.001),while there was no significant difference in these parameters between before acupuncture and two hours after acupuncture(P>0.05);③when acupuncture had the strongest deqi,there were positive correlations between gastrin,plasma prokinetic hormone,cholecystokinin,and secretin values and CTTs of arterial-muscle,muscle-venous,and arterial-venous(r=0.360-0.702,P<0.001).Conclusion Acupuncture of the Zusanli,when it gains the strongest deqi,can cause changes in the microcirculation around the skeletal muscle,leading to a significant shortening of CTTs,and also promotes the secretory function of the gastrointestinal tract.

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca²⁺ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca²⁺ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca²⁺ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.
Mice ; Animals ; Primary Visual Cortex ; Extinction, Psychological/physiology* ; Learning/physiology* ; Fear/physiology* ; Hippocampus/physiology*