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.

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*

Endoplasmic reticulum stress(ERS)is associated with the pathophysiology of various lung diseases.Multiple experiments have confirmed that inhibiting ERS can alleviate inflammatory responses,improve lung function,and possess certain anti-infective effects.ERS inhibitors can positively impact the treatment of respiratory system diseases by targeting the unfolded protein response(UPR)in the ERS pathway and regulating the balance of calcium ions within the endoplasmic reticulum.Most current research on ERS inhibitors is still in the preclinical stage.This article thoroughly reviews the relevant reviews and various experimental research results on ERS in respiratory diseases,systematically examining the potential roles of the main branches of UPR,including inositol requiring enzyme 1 alpha(IRE 1α),protein kinase-like endoplasmic reticulum kinase(PERK),and activated transcription factor 6(ATF6),as well as other ERS inhibitors in respiratory diseases.The aim is to promote clinical trial exploration of ERS inhibitors,with the hope of providing effective drug selection strategies for the treatment and symptom relief of respiratory diseases.

Objective To investigate the effects of different inspired oxygen concentrations on periop-erative cerebrovascular function in patients with a history of ischemic stroke.Methods A total of 150 patients scheduled for elective surgery with a history of ischemic stroke were enrolled from Renji Hospital,Shanghai Jiao Tong University School of Medicine,between June 2020 and March 2024.Using a random number table,patients were allocated into two groups:F30 group(intraoperative fraction of inspired oxygen,FiO2=30%)and F80 group(FiO2=80%),with 75 patients in each group.Bilateral middle cerebral artery(MCA)blood flow was continu-ously monitored using transcranial Doppler(TCD),including mean flow velocity(Vm),resistance index(RI),and pulsatility index(PI).Cerebral oxygen saturation(rScO2)was measured using a FORE-SIGHT oximeter.Arterial blood gas analysis was performed preoperatively,1 hour after induction,and before extubation to assess pH,partial pressure of arterial carbon dioxide(PaCO2),oxygenation index(OI),base excess(BE),hematocrit(Hct),and lactate(Lac).Peripheral blood samples were collected 24 hours postoperatively to measure thrombox-ane A2(TXA2)and prostacyclin(PGI2)levels.At 1 month postoperatively,telephone follow-up was conducted to evaluate the risk of recurrent cerebral ischemic events using the ABCD2 score and Essen Stroke Risk Score(ESRS).Results No significant differences were observed in baseline characteristics between the two groups.Perioperative arterial blood gas parameters did not differ significantly between groups(P>0.05).Compared with the F30 group,the F80 group exhibited a smaller reduction in mean flow velocity(Vm)of the affected MCA at the end of surgery(8.18%±3.34%vs.13.57%±5.32%,P<0.05),while no significant intergroup differences were found in RI or PI.At 1 hour after induction and before extubation,rScO2 of the affected hemisphere was signifi-cantly increased in the F80 group as compared with the F30 group(P<0.05),whereas no significant difference was observed in the contralateral hemisphere.Before extubation and on postoperative day 1,TXA2 levels were significantly lower and PGI2 levels higher in F80 group compared with F30 group(P<0.05).The proportion of patients at high risk of cerebral ischemia by ABCD2 and ESRS at 1 month postoperatively did not differ between groups(P>0.05).Conclusion In patients with a history of stroke,intraoperative administration of 80%FiO2under general anesthesia better maintains perioperative cerebral hemodynamic stability and cerebral oxygen satura-tion,improves cerebrovascular endothelial function,but does not significantly affect the short-term incidence of postoperative cerebrovascular events compared with 30%FiO2.

Endoplasmic reticulum stress(ERS)is associated with the pathophysiology of various lung diseases.Multiple experiments have confirmed that inhibiting ERS can alleviate inflammatory responses,improve lung function,and possess certain anti-infective effects.ERS inhibitors can positively impact the treatment of respiratory system diseases by targeting the unfolded protein response(UPR)in the ERS pathway and regulating the balance of calcium ions within the endoplasmic reticulum.Most current research on ERS inhibitors is still in the preclinical stage.This article thoroughly reviews the relevant reviews and various experimental research results on ERS in respiratory diseases,systematically examining the potential roles of the main branches of UPR,including inositol requiring enzyme 1 alpha(IRE 1α),protein kinase-like endoplasmic reticulum kinase(PERK),and activated transcription factor 6(ATF6),as well as other ERS inhibitors in respiratory diseases.The aim is to promote clinical trial exploration of ERS inhibitors,with the hope of providing effective drug selection strategies for the treatment and symptom relief of respiratory diseases.

Objective To investigate the effects of different inspired oxygen concentrations on periop-erative cerebrovascular function in patients with a history of ischemic stroke.Methods A total of 150 patients scheduled for elective surgery with a history of ischemic stroke were enrolled from Renji Hospital,Shanghai Jiao Tong University School of Medicine,between June 2020 and March 2024.Using a random number table,patients were allocated into two groups:F30 group(intraoperative fraction of inspired oxygen,FiO2=30%)and F80 group(FiO2=80%),with 75 patients in each group.Bilateral middle cerebral artery(MCA)blood flow was continu-ously monitored using transcranial Doppler(TCD),including mean flow velocity(Vm),resistance index(RI),and pulsatility index(PI).Cerebral oxygen saturation(rScO2)was measured using a FORE-SIGHT oximeter.Arterial blood gas analysis was performed preoperatively,1 hour after induction,and before extubation to assess pH,partial pressure of arterial carbon dioxide(PaCO2),oxygenation index(OI),base excess(BE),hematocrit(Hct),and lactate(Lac).Peripheral blood samples were collected 24 hours postoperatively to measure thrombox-ane A2(TXA2)and prostacyclin(PGI2)levels.At 1 month postoperatively,telephone follow-up was conducted to evaluate the risk of recurrent cerebral ischemic events using the ABCD2 score and Essen Stroke Risk Score(ESRS).Results No significant differences were observed in baseline characteristics between the two groups.Perioperative arterial blood gas parameters did not differ significantly between groups(P>0.05).Compared with the F30 group,the F80 group exhibited a smaller reduction in mean flow velocity(Vm)of the affected MCA at the end of surgery(8.18%±3.34%vs.13.57%±5.32%,P<0.05),while no significant intergroup differences were found in RI or PI.At 1 hour after induction and before extubation,rScO2 of the affected hemisphere was signifi-cantly increased in the F80 group as compared with the F30 group(P<0.05),whereas no significant difference was observed in the contralateral hemisphere.Before extubation and on postoperative day 1,TXA2 levels were significantly lower and PGI2 levels higher in F80 group compared with F30 group(P<0.05).The proportion of patients at high risk of cerebral ischemia by ABCD2 and ESRS at 1 month postoperatively did not differ between groups(P>0.05).Conclusion In patients with a history of stroke,intraoperative administration of 80%FiO2under general anesthesia better maintains perioperative cerebral hemodynamic stability and cerebral oxygen satura-tion,improves cerebrovascular endothelial function,but does not significantly affect the short-term incidence of postoperative cerebrovascular events compared with 30%FiO2.

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.

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.