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 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 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 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 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.

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.

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.