Objective To explore the regulatory effect of moderate intensity aerobic exercise on glu-cose and lipid metabolism disordersafter immune stimulation in high-fat diet induced insulin resistance(IR)mice by inducing tolerance of trained immunity.Methods Eighteen of 70 male C57BL/6 male mice were randomly selected as the control group(CON group),while the remaining mice were subjected to high-fat diet intervention(HFD group)for 8 weeks.After modeling,six of the CON group and HFD group were measured their glucose and lipid metabolism and inflammation levels.The remaining mice in the HFD group were randomly divided into HFD sedentary group(HS group)and HFD exer-cise group(HE group),each of 16.The HE groups underwent a daily 60-minute running on a hori-zontal treadmill at 12 m/min,5 days a week for 8 weeks.After that,the CON,HS and HE groups were randomly divided into an immune stimulation group(lipopolysaccharides,LPS group)and a con-trol group(phosphate buffered saline,PBS group),with 6 in CON-PBS and CON-LPS groups,and 8 in HS-PBS,HS-LPS,HE-PBS and HE-LPS groups.The LPS group received intraperitoneal injec-tion of LPS as an immune stimulus,and were taken samples 24 hours after intervention.During the intervention period,the body weight,food intake,fasting blood glucose(FBG),glucose tolerance,and insulin tolerance were tested for all groups.Then,the serum blood lipid level was tested.More-over,the levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and interleukin-10(IL-10)in serum were detected by using the enzyme-linked immunosorbent assay,while the protein expression of IL-1β,IL-10,induciblenitricoxidesynthase(iNOS)andarginase-1(Arg-1)were measured by using Western Blot.Results(1)After 8 weeks of high-fat diet intervention,compared with the CON group,there was a significant increase in the body weight,food intake,and FBG,the level of TNF-α and IL-1β in serum and expressions of IL-1β and iNOS in liver,skeletal muscle and adipose tissue,but a significant decrease in glucose and insulin tolerance,the level of anti-in-flammatory factor IL-10,as well as IL-10 and Arg-1 in liver and Arg-1 in adipose tissues in group HFD(P<0.01,P<0.05).(2)After 8 weeks of diet intervention,the body weight of group HS-PBS was still significantly higher than group CON-PBS(P<0.01).However,no significant differences were found between group CON-PBS and HS-PBS in other indicators(P>0.05).After LPS intervention,the food intake of both CON-LPS and HS-LPS groups was significantly lower than the corresponding PBS group(P<0.05).However,the levels of FBG,TG,TC,LDL-C,TNF-α and IL-1β in serum,IL-1β and iNOS in liver and adipose tissues,and iNOS in skeletal muscles of group HS-LPS were signif-icantly higher compared with group HS-PBS and CON-LPS(P<0.05).Meanwhile,the levels of IL-10 in serum,skeletal muscles and adipose tissues,and Arg-1 in skeletal muscles and adipose tissues of group HS-LPS decreased significantly compared with group HS-PBS and CON-LPS(P<0.05).(3)Af-ter simultaneous aerobic exercise intervention,there were no significant differences between group HE-LPS and HE-PBS in FBG,TC,LDL-C,TNF-α,IL-1β and IL-10 in serum,as well as IL-1β,iN-OS and IL-10 in the liver,skeletal muscles and adipose tissues(P>0.05).Moreover,thelevels of FBG,TG,TC,TNF-α,IL-1β in serum,and IL-1β and iNOS in the liver,skeletal muscle and adi-pose tissue decreased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Howev-er,the levels of IL-10 in the serum and liver,and IL-10 and Arg-1 in skeletal muscles and adi-pose tissues increased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Conclu-sion Eight-week aerobic exercise can effectively relieve the glucose and lipid metabolism disorder after immune stimulation in IR mice,which may be related to the stimulation of immunologic tolerance in innate immune cells,thereby reducing the excessive inflammatory response caused by secondary im-mune stimulation.

Objective:To investigate the application value of Bama miniature pig model in endoscopic retrograde cholangiopancreatography (ERCP) training.Methods:The experimental study was conducted. Six Bama miniature pigs were selected to establish animal model for ERCP operation. The experimental equipments were the EP-6000 image processing system and ED-580T therapeutic duodenoscopy, and the surgery was performed by two experienced chief physicians. Observation indicators: (1) surgical operation status; (2) preoperative and postoperative physiological and biochemical indicators of experimental animals; (3) experimental endpoint indicators. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers. Results:(1) Surgical operation status. During the operation, the time required for the duodenoscope to pass from the esophageal inlet to the pylorus of the six experimental animals was 151(range, 46-227)seconds, the insertion length of the endoscope at the pylorus was 85(range, 80-90)cm, and the straightened length of the endoscope shaft was 47(range, 45-50)cm. For bile duct cannulation, the total number of cannulation attempts was 2.0(range, 1.0-3.0), the number of successful cannulation was 1.5(range, 1.0-2.0), and the time of successful cannulation was 44(range, 13-80)seconds. For pancreatic duct cannulation, the total number of cannulation attempts was 3.0(range, 1.0-8.0), and only one successful intubation was performed for each experimental animal, with the time of successful cannulation as 100(range, 53-320)seconds. (2) Preoperative and postoperative physiological and biochemical indicators of experimental animals. For six experimental animals, the preoperative body temperature was (38.8±0.1)℃, serum amylase was (55.3±0.2)U/dL, serum lipase was 232.9(range, 29.4-547.3)U/L, alanine aminotransferase was (51±10)U/L, aspartate aminotransferase was (38±12)U/L, and total bilirubin was (3.2±0.7)μmol/L. At 24 hours postoperatively, the body temperature was (38.6±0.1)℃, serum amylase was (53.0±6.0)U/dL, serum lipase was 62.4(range, 29.4-94.1)U/L, alanine amino-transferase was (54±5)U/L, aspartate aminotransferase was (67±27)U/L, and total bilirubin was (3.5±1.9)μmol/L. (3) Experimental endpoint indicators. At the experimental endpoint of 14 days after surgery, the bile duct length in the six experimental animals was (8.6±1.2)cm, and the bile duct inner diameter was (2.5±0.5)mm. The pancreatic duct length was 12.9(range, 3.7-20.8)cm, and the inner diameter was (1.6±0.2)mm. Results of histopathological examination revealed that both CD3 and CD68 staining were negative in the bile duct and surrounding hepatic tissue, as well as in the pancreatic duct and adjacent pancreatic tissue at the experimental endpoint of 14 days after surgery.Conclusion:Bama miniature pig model can be used for ERCP training.

Objective To explore the regulatory effect of moderate intensity aerobic exercise on glu-cose and lipid metabolism disordersafter immune stimulation in high-fat diet induced insulin resistance(IR)mice by inducing tolerance of trained immunity.Methods Eighteen of 70 male C57BL/6 male mice were randomly selected as the control group(CON group),while the remaining mice were subjected to high-fat diet intervention(HFD group)for 8 weeks.After modeling,six of the CON group and HFD group were measured their glucose and lipid metabolism and inflammation levels.The remaining mice in the HFD group were randomly divided into HFD sedentary group(HS group)and HFD exer-cise group(HE group),each of 16.The HE groups underwent a daily 60-minute running on a hori-zontal treadmill at 12 m/min,5 days a week for 8 weeks.After that,the CON,HS and HE groups were randomly divided into an immune stimulation group(lipopolysaccharides,LPS group)and a con-trol group(phosphate buffered saline,PBS group),with 6 in CON-PBS and CON-LPS groups,and 8 in HS-PBS,HS-LPS,HE-PBS and HE-LPS groups.The LPS group received intraperitoneal injec-tion of LPS as an immune stimulus,and were taken samples 24 hours after intervention.During the intervention period,the body weight,food intake,fasting blood glucose(FBG),glucose tolerance,and insulin tolerance were tested for all groups.Then,the serum blood lipid level was tested.More-over,the levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and interleukin-10(IL-10)in serum were detected by using the enzyme-linked immunosorbent assay,while the protein expression of IL-1β,IL-10,induciblenitricoxidesynthase(iNOS)andarginase-1(Arg-1)were measured by using Western Blot.Results(1)After 8 weeks of high-fat diet intervention,compared with the CON group,there was a significant increase in the body weight,food intake,and FBG,the level of TNF-α and IL-1β in serum and expressions of IL-1β and iNOS in liver,skeletal muscle and adipose tissue,but a significant decrease in glucose and insulin tolerance,the level of anti-in-flammatory factor IL-10,as well as IL-10 and Arg-1 in liver and Arg-1 in adipose tissues in group HFD(P<0.01,P<0.05).(2)After 8 weeks of diet intervention,the body weight of group HS-PBS was still significantly higher than group CON-PBS(P<0.01).However,no significant differences were found between group CON-PBS and HS-PBS in other indicators(P>0.05).After LPS intervention,the food intake of both CON-LPS and HS-LPS groups was significantly lower than the corresponding PBS group(P<0.05).However,the levels of FBG,TG,TC,LDL-C,TNF-α and IL-1β in serum,IL-1β and iNOS in liver and adipose tissues,and iNOS in skeletal muscles of group HS-LPS were signif-icantly higher compared with group HS-PBS and CON-LPS(P<0.05).Meanwhile,the levels of IL-10 in serum,skeletal muscles and adipose tissues,and Arg-1 in skeletal muscles and adipose tissues of group HS-LPS decreased significantly compared with group HS-PBS and CON-LPS(P<0.05).(3)Af-ter simultaneous aerobic exercise intervention,there were no significant differences between group HE-LPS and HE-PBS in FBG,TC,LDL-C,TNF-α,IL-1β and IL-10 in serum,as well as IL-1β,iN-OS and IL-10 in the liver,skeletal muscles and adipose tissues(P>0.05).Moreover,thelevels of FBG,TG,TC,TNF-α,IL-1β in serum,and IL-1β and iNOS in the liver,skeletal muscle and adi-pose tissue decreased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Howev-er,the levels of IL-10 in the serum and liver,and IL-10 and Arg-1 in skeletal muscles and adi-pose tissues increased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Conclu-sion Eight-week aerobic exercise can effectively relieve the glucose and lipid metabolism disorder after immune stimulation in IR mice,which may be related to the stimulation of immunologic tolerance in innate immune cells,thereby reducing the excessive inflammatory response caused by secondary im-mune stimulation.

Objective:To investigate the predictive value of endothelial activation and stress index(EASIX)for the prognosis of patients with mantle cell lymphoma(MCL).Methods:A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023,had therapeutic indications and received standard treatment.Results:A total of 66 patients were included and divided into high EASIX group and low EASIX group,according to a cutoff value of 0.97 determined by the receiver operating characteristic(ROC)curve.Multivariate Cox regression analysis showed that prealbumin＜0.2 g/L,high EASIX,and ECOG PS score ≥2 were independent risk factors influencing overall survival(OS)in MCL patients.The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months,and the median progression-free survival was 8.8 and 26.0 months,respectively.The proportions of patients with ECOG PS score ≥2 and prealbumin＜0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group.Conclusion:At the time of initial diagnosis,EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL.Furthermore,patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.

The advancement of surgical techniques enables effective treatment for many patients with oral and maxillofacial tumors.How-ever,post-surgery problems such as chewing,swallowing and speech difficulty may arise due to the defects in speech organs and inade-quate compensatory function of tissue flap repair.Speech disorders,in particular,isolate patients by making it difficult for them to com-municate with others,not only impact their quality of life but also potentially lead to psychological problems and social interaction disor-ders.Although the decline in life quality and other related issues caused by speech dysfunction due to surgery and radiotherapy or chemo-therapy have been widely recognized,there is currently no standardized and universally applicable assessment method and standardized re-habilitation treatment management guideline or consensus for speech disorders following oral and maxillofacial tumor surgery at home and abroad.Based on previous clinical practice,combined with the characteristics of speech disorders in patients after oral and maxillofacial tumor surgery,the clinical experience of the experts in maxillofacial tumor surgery and rehabilitation and the relevant domestic and foreign literature,relevant experts organized discussions and modifications,reach a consensus on core content such as the assessment of speech disorders and the implementation plan for early rehabilitation treatment management,providing a reference for clinical practice,in order to improve patients'speech-related life quality and enhance the assessment and rehabilitation treatment techniques for speech disorders after oral and maxillofacial tumor surgery.

Objective:To investigate the application value of Bama miniature pig model in endoscopic retrograde cholangiopancreatography (ERCP) training.Methods:The experimental study was conducted. Six Bama miniature pigs were selected to establish animal model for ERCP operation. The experimental equipments were the EP-6000 image processing system and ED-580T therapeutic duodenoscopy, and the surgery was performed by two experienced chief physicians. Observation indicators: (1) surgical operation status; (2) preoperative and postoperative physiological and biochemical indicators of experimental animals; (3) experimental endpoint indicators. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers. Results:(1) Surgical operation status. During the operation, the time required for the duodenoscope to pass from the esophageal inlet to the pylorus of the six experimental animals was 151(range, 46-227)seconds, the insertion length of the endoscope at the pylorus was 85(range, 80-90)cm, and the straightened length of the endoscope shaft was 47(range, 45-50)cm. For bile duct cannulation, the total number of cannulation attempts was 2.0(range, 1.0-3.0), the number of successful cannulation was 1.5(range, 1.0-2.0), and the time of successful cannulation was 44(range, 13-80)seconds. For pancreatic duct cannulation, the total number of cannulation attempts was 3.0(range, 1.0-8.0), and only one successful intubation was performed for each experimental animal, with the time of successful cannulation as 100(range, 53-320)seconds. (2) Preoperative and postoperative physiological and biochemical indicators of experimental animals. For six experimental animals, the preoperative body temperature was (38.8±0.1)℃, serum amylase was (55.3±0.2)U/dL, serum lipase was 232.9(range, 29.4-547.3)U/L, alanine aminotransferase was (51±10)U/L, aspartate aminotransferase was (38±12)U/L, and total bilirubin was (3.2±0.7)μmol/L. At 24 hours postoperatively, the body temperature was (38.6±0.1)℃, serum amylase was (53.0±6.0)U/dL, serum lipase was 62.4(range, 29.4-94.1)U/L, alanine amino-transferase was (54±5)U/L, aspartate aminotransferase was (67±27)U/L, and total bilirubin was (3.5±1.9)μmol/L. (3) Experimental endpoint indicators. At the experimental endpoint of 14 days after surgery, the bile duct length in the six experimental animals was (8.6±1.2)cm, and the bile duct inner diameter was (2.5±0.5)mm. The pancreatic duct length was 12.9(range, 3.7-20.8)cm, and the inner diameter was (1.6±0.2)mm. Results of histopathological examination revealed that both CD3 and CD68 staining were negative in the bile duct and surrounding hepatic tissue, as well as in the pancreatic duct and adjacent pancreatic tissue at the experimental endpoint of 14 days after surgery.Conclusion:Bama miniature pig model can be used for ERCP training.

To promote the high-quality development of healthcare in the highland areas and to enable traditional Chinese medicine(TCM)to make a more prominent contribution to the healthcare of the people in these areas,it is imperative to clarify the roles of TCM in the formation of the healthcare system in the past and present,as well as the direction of innovative development of TCM in the plateau in the future.To this end,this paper first systematically reviews the literature to summarize the influence of TCM on the cultural background,theoretical framework,and practical system of Tibetan medicine during its origin,development,and maturation;then,through the example of typical cases,it elaborates on the direct practical applications of TCM in the prevention and treatment of a series of highland diseases from the perspectives of pathogenesis,therapeutic principles,unique drugs,and techniques;finally,it deeply reflects on a series of problems restricting the integration,inheritance,and innovative development of TCM in the highland areas and puts forward targeted suggestions to enable TCM to serve and safeguard the health of people living in the plateaus better together with the local ethnic medicine.

AIM:To investigate the regulatory role and molecular mechanisms of the p62-NIMA(never in mi-tosis gene A)-related kinase 7(NEK7)-gasdermin D(GSDMD)-mediated pyroptosis axis in a mouse model of gouty arthri-tis.METHODS:C57BL/6 mice were randomly divided into control group,model group,and colchicine group(n=5 per group).Conditional knockout mouse models of p62,GSDMD,and p62-GSDMD were constructed and assigned to p62-/-group,GSDMD-/-group,and p62-/--GSDMD-/-group,respectively(n=5 per group).The gouty arthritis model was in-duced by monosodium urate crystal injection into the ankle joint in all groups except control.The colchicine group re-ceived oral colchicine pretreatment for 3 days prior to MSU injection,continuing for 5 days total.Ankle joint swelling was measured using a vernier caliper at 0,6,12,24,and 48 hours post-injection.Serum levels of p62,GSDMD,caspase-1,interleukin-1β(IL-1β),and IL-18 were quantified by ELISA.Immunohistochemistry staining was performed to assess nu-cleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein contain-ing a caspase recruitment domain(ASC),cleaved caspase-1,and IL-1β expression in joint tissues.Western blot was con-ducted to detect protein expression of p62,GSDMD,NLRP3,ASC,cleaved caspase-1,and IL-1β in mouse ankle joints,while RT-qPCR was used to measure mRNA expression of p62,NEK7,GSDMD,NLRP3,caspase-1 and IL-1β.RE-SULTS:Serum p62 levels and p62 protein and mRNA expression in ankle joints were significantly elevated in the model group.Following p62 gene knockout,the protein expression of NLRP3,ASC,caspase-1,and IL-1β in ankle joints showed a marked increase.Both GSDMD-/-and p62-/--GSDMD-/-groups exhibited attenuated ankle joint swelling,reduced serum levels of caspase-1,IL-1β,and IL-18,along with downregulated expression of p62,NLRP3,ASC,caspase-1,and IL-1β at both mRNA and protein levels in ankle joints.The NEK7 mRNA expression was similarly suppressed in these groups.CONCLUSION:Our findings demonstrate that MSU crystals activate macrophages through the coordinated action of p62,NEK7,and GSDMD,triggering NLRP3 inflammasome-mediated pyroptosis and ultimately promoting joint inflammation in gout mice.The p62-NEK7-GSDMD axis represents a critical regulatory mechanism in the canonical pyrop-tosis signaling pathway.

Objective:To investigate disease characteristics of patients with psoriatic arthritis (PsA) based on the PsA cohort in West China Hospital, so as to provide a reference for clinicians in its diagnosis, treatment, and evaluation strategy formulation.Methods:A cross-sectional study was carried out, and a descriptive analysis was conducted on clinical data from PsA patients who were treated at the Department of Dermatology, West China Hospital, Sichuan University between April 2, 2020, and January 21, 2025. Demographic characteristics, clinical manifestations, laboratory and imaging findings, and treatment modalities were analyzed.Results:A total of 530 PsA patients were included, of whom 332 (62.6%) were males and 198 (37.4%) were females, with ages of 44.1 ± 12.4 years. Skin lesions preceded joint symptoms in 452 patients (85.3%), with time intervals ( M [ Q1, Q3]) of 8.0 (3.0, 15.0) years. Overweight or obesity was observed in 319 patients (60.2%), and 188 (35.5%) had comorbid fatty liver. Peripheral joint involvement was common (485 cases, 91.5%), with the proximal interphalangeal joints being most frequently affected by tenderness (172 cases, 35.5%) and swelling (119 cases, 24.5%) ; the number of enthesitis cases identified by ultrasonography (116 cases, 23.9%) was significantly higher than that by clinical examination (82 cases, 15.5%) ; axial joint involvement was observed in 258 patients (48.7%), with the sacroiliac joints most commonly affected (201 cases, 77.9%). Regarding treatment, conventional systemic drugs were predominant in the treatment of psoriasis prior to the diagnosis of PsA; after the diagnosis of PsA, the number of patients receiving targeted therapies increased to 334 (63.0%), with interleukin-17 inhibitors being the most common (140 cases, 26.4%), followed by tumor necrosis factor-α inhibitors (106 cases, 20.0%) and Janus kinase inhibitors (39 cases, 7.4%) . Conclusions:PsA predominantly affects males over 40 years old and is characterized by preceding skin lesions, delayed diagnosis, and multiple comorbidities. High-frequency ultrasound has advantages in the early detection of peripheral enthesitis. Further attention is needed for managing comorbidities such as fatty liver and obesity-related metabolic conditions.

AIM:This study aims to investigate the mechanisms underlying skeletal muscle mitochondrial damage associated with decline in exercise function during high-altitude de-adaptation,using a mouse model.METHODS:Twen-ty-four healthy male C57BL/6J mice were randomly assigned to two groups:a high-altitude de-adaptation group and a plain control group.The model group was exposed to a low-pressure,low-oxygen chamber simulating an altitude of 7 000 meters for two weeks,followed by eight days of rearing in a plain environment.The control group was maintained in a plain envi-ronment for the same duration.Grip strength and pole-climbing tests were conducted on the 1st,3rd,and 5th days post-re-turn to assess muscle strength and motor coordination.Treadmill exercises were performed on the 4th and 8th days to eval-uate exercise endurance.After the treadmill exercise on the 8th day,serum,liver,and skeletal muscle tissues were col-lected.Levels of lactic acid(LA),glucose(GLU),creatine kinase(CK),lactate dehydrogenase(LDH),alanine trans-aminase(ALT),and aspartate aminotransferase(AST)in serum,as well as glycogen levels in the liver and muscle,were analyzed.Additionally,the expression of proteins related to mitochondrial biogenesis,fission,fusion,and oxidative phos-phorylation in muscle tissues was assessed using Western blot.RESULTS:(1)The model group exhibited significant re-ductions in grip strength,increased pole-climbing T-turn and total times,and decreased total time and distance in the ex-haustion running test.(2)Serum levels of LA,CK,LDH,ALT,and AST were elevated,while GLU levels decreased,and glycogen levels in both the liver and muscle were reduced in the model group following the treadmill exercise.(3)Ab-normal indicators in the model group did not return to normal by the end of the de-adaptation period.(4)Western blot analysis revealed decreased expression of mitochondrial oxidative phosphorylation proteins(ATP6V1A and Mt-CO2)and mitochondrial biogenesis proteins(PGC-1α and FGF21),increased levels of mitochondrial fusion proteins(OPA1 and MFN1),and no significant changes in fission protein expression(FIS1 and DRP1)in muscle tissue from the model group.CONCLUSION:Exercise capacity in mice during the high-altitude de-adaptation period significantly declined,particu-larly in terms of muscle strength,motor coordination,and endurance.This decline is closely associated with abnormal pro-tein expression related to skeletal muscle mitochondrial energy metabolism and production.