ObjectiveTo investigate the mechanism by which activation of α7nicotinic acetylcholine receptors （α7nAChR） optimizes brown adipose tissue （BAT） thermogenesis in obese mice. MethodsObesity was induced in C57BL/6J mice via a high-fat diet. Fifty 8-week-old mice were randomly assigned to five groups： low-fat diet （Control）， high-fat diet （HFD）， high-fat diet plus a β3-adrenergic receptor agonist （HFD+β3）， high-fat diet plus a β3-adrenergic receptor agonist and an α7nAChR selective agonist （HFD+β3+GTS-21）， and high-fat diet plus a β3-adrenergic receptor agonist and an α7nAChR selective antagonist （HFD+β3+α-BGT）. Haematoxylin and eosin （HE） staining was used to evaluate BAT morphology. Transmission electron microscopy was performed to assess mitochondrial number and lipid droplet morphology in adipocytes. ELISA was used to measure levels of tumour necrosis factor-α （TNF-α）， interleukin（IL）-1β，IL-10， transforming growth factor-β （TGF-β）， cyclic adenosine monophosphate （cAMP）， and norepinephrine （NE）. RT-qPCR was conducted to determine mRNA expression levels of vascular endothelial growth factor A （VEGF-A）， nitric oxide synthase 2 （NOS2）， arginase 1 （Arg1）， uncoupling protein 1 （UCP1）， PR domain-containing protein 16 （PRDM16）， and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in BAT. Immunohistochemistry was used to detect macrophage markers （CD31， CD86， and CD206）. Protein expression levels of UCP1， α7nAChR， nuclear factor-κB p65（NF-κB p65）， phosphorylated Janus kinase 2 （p-JAK2）， and phosphorylated signal transducer and activator of transcription 3 （p-STAT3） were analyzed by Western blot. ResultsCompared with the Control group， the HFD group showed enlarged lipid droplets and reduced mitochondrial numbers in adipocytes， accompanied by increased TNF-α and IL-1β and decreased IL-10， TGF-β， Arg1， and VEGF-A （all P<0.01）. Compared with the HFD+β3 group， the HFD+β3+GTS-21 group showed a smaller lipid droplet area and a higher mitochondrial number， along with reduced levels of pro-inflammatory factors， NOS2， and NF-κB p65， and increased levels of anti-inflammatory factors， Arg1， and phosphorylation of JAK2 and STAT3 （all P<0.01）. ConclusionActivation of α7nAChR in combination with a β3-adrenergic receptor agonist effectively enhances thermogenesis， alleviates local adipose tissue hypoxia， and shifts the local inflammatory phenotype toward an M2-like state， thereby reducing inflammation in brown adipose tissue and improving its thermogenic capacity.

Objective:To investigate the clinical subtypes of acute aortic dissection (AAD) through latent class analysis.Methods:This study was a multicenter retrospective cohort study. Patients with AAD admitted to five hospitals, including Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Henan Provincial People′s Hospital, Central China Fuwai Hospital of Zhengzhou University (Fuwai Central China Cardiovascular Hospital), the Third Affiliated Hospital of Xinxiang Medical University and the Second Affiliated Hospital of Chongqing Medical University, between August 2010 and December 2021 were enrolled. Based on clinical and biological characteristics, latent class analysis (models with 2 to 5 latent classes) was conducted to classify the enrolled patients. The optimal classification scheme was determined using model fitting evaluations, including log-likelihood (LL), entropy, Lo-Mendell-Rubin adjusted likelihood ratio test and so on. Clinical data of different subtypes were compared, and in-hospital mortality was analyzed across the entire population and among subgroups receiving different treatments.Results:A total of 2 689 AAD patients, aged 54 (46, 63) years were included, with 1 305 (48.5%) having DeBakey type Ⅰ, 156 (5.8%) type Ⅱ, and 1 228 (45. 7%) type Ⅲ dissections. The cohort comprised 2 134 (79.4%) males. The overall in-hospital mortality rate was 22.8% (613/2 689). Latent class analysis indicated that a two-class model was optimal (LL=147 413.242, entropy=0.812, and PLMRT<0.001). Patients were classified into two subtypes, named clinical subtype 1 and clinical subtype 2. Compared to clinical subtype 1, clinical subtype 2 had a higher proportion of females, was older, had more dissections involving the ascending aorta, and exhibited higher rates of organ dysfunction (elevated alanine aminotransferase and creatinine levels) and inflammatory response (neutrophilia) (all P<0.05). Clinical subtype 2 also showed higher in-hospital mortality compared to subtype 1 (26.3% (238/905) vs. 21.0% (375/1 784), P=0.002). Among patients undergoing surgical treatment, clinical subtype 2 had higher mortality than subtype 1 (40.1% (67/167) vs. 30.0% (101/337), P=0.027). However, no significant differences in mortality were observed between the two subtypes among patients receiving medical therapy or endovascular and hybrid procedures (all P>0.05). Conclusions:Comprehensive latent class analysis identifies two subtypes of AAD with distinct clinical characteristics and treatment responses. These findings provide new insights into individualized clinical decision-making and prognostic evaluation for AAD patients.

Objective:To investigate the external quality control assessment results of iodine deficiency disorders (IDD) laboratories at all levels in Yunnan Province, so as to provide technical support for IDD monitoring.Methods:In 2023, all IDD laboratories at provincial, city (prefecture) and county level in Yunnan Province tested the assessment samples randomly provided by the National IDD Reference Laboratory based on their participation in external quality control assessment projects (urinary iodine, salt iodine, water iodine). For laboratories that do not use fully automatic iodine detectors, urinary iodine detection was carried out using the "Determination of Iodine in Urine - Part 1: As 3+-Ce 4+ Catalytic Spectrophotometry" (WS/T 107.1-2016), salt iodine detection was carried out using the direct titration method in the "General Test Methods in Salt Industry-Determination of Iodine"(GB/T 13025.7-2012), and water iodine detection was carried out using the cerium sulfate catalytic spectrophotometry. The test results were evaluated using standard value ± uncertainty. Results:A total of 146 IDD laboratories in Yunnan Province participated in the external quality control assessment, including 1 at the provincial level, 16 at the city (prefecture) level, and 129 at the county level. The feedback rate and qualification rate of urinary iodine, salt iodine in the provincial, city (prefecture) and county level IDD laboratories were all 100% (146/146). The feedback rate and the qualified rate of urinary iodine, salt iodine and water iodine in county level IDD laboratories were all 100%(17/17).Conclusion:In 2023, all external quality control assessment results of IDD laboratories in Yunnan Province are qualified, with stable testing quality, providing reliable laboratory technical support for IDD monitoring.

Objective:To explore the therapeutic efficacy and prognostic factors of combined rituximab and intensive chemotherapy for sporadic adult Burkitt lymphoma (BL) .Methods:This retrospective study examined the clinical and survival data of 30 patients newly diagnosed with BL between July 2011 and February 2023 at the Blood Diseases Hospital. Kaplan-Meier method was used for survival analysis, and the log-rank test was used for univariate analysis of prognostic factors.Results:The median age of the 30 patients was 43 years (24 - 66 years), and the male to female ratio was 3: 2. Extranodal invasion was present in 80% of the patients, with involvement of the bone marrow in 53.3% and central nervous system in 10.0%. The Ann Arbor stage was Ⅲ and Ⅳ in 86.7%. According to the number of Burkitt Lymphoma International Prognostic Index (BL-IPI) risk factors, patients were classified as low risk (0) in 20.0%, intermediate risk (1) in 43.3%, and high risk (≥2) in 36.7%. All patients were treated with an induction regimen of rituximab combined with intensive chemotherapy, with objective and complete response rates of 80.0% and 76.7%, respectively. The median follow-up was 49 months (6-153 months), and the 5-year progression-free survival (PFS) and overall survival (OS) rates were both (76.7±7.7) %. All patients with limited stage ( n=4) achieved continuous complete remission (CCR). Patients who had high risk, advanced stage sensitive to induction therapy ( n=10) sequentially received first-line autologous hematopoietic stem cell transplantation (auto-HSCT) as consolidation therapy; 9 patients achieved CCR, whereas 1 patient with central nervous system invasion developed early disease progression and died. The BL-IPI low, intermediate, and high risk groups had respective 5-year PFS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0069) and OS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0075). The main adverse effects of induction therapy were myelosuppression and secondary infections, which were effectively managed by appropriate symptomatic treatment. Univariate analysis demonstrated that worse PFS was associated with BL-IPI score ≥2 ( HR=4.90, 95% CI 1.02-23.45, P=0.0329) ; extranodal invasion at ≥2 sites ( HR=12.62, 95% CI 2.59-61.62, P=0.0021) ; and failure to achieve first complete response (CR1) after induction therapy ( HR=31.86, 95% CI 4.19-242.20, P<0.0001) . Conclusions:Intensive immunochemotherapy regimens were effective and well-tolerated by adult patients with highly aggressive BL. Treatment efficacy was ideal in patients with limited-stage disease, whereas prognosis was unsatisfactory in patients with high-risk BL-IPI. Sequential first-line auto-HSCT consolidation therapy may further improve outcomes in patients with high-risk advanced-stage disease who are sensitive to induction therapy. BL-IPI score ≥2, extranodal invasion at ≥2 sites, and failure to achieve CR1 after induction therapy were adverse prognostic factors in adult patients with BL.

AIM:To explore the mechanism by which activation of α7 nicotinic acetylcholine receptor(nAChR)in combination with cold stimulation promotes the beiging of white adipose tissues in obese mice.METHODS:Male C57BL/6J mice,aged 8 weeks,were acclimated for 1 week before fed with high-fat diet(HFD)for 12 weeks to estab-lish an obese model.Fifty mice were randomly divided into 5 groups:control group(low-fat diet),HFD group,model group(HFD+cold stimulation),agonist group(HFD+cold stimulation+α7 nAChR agonist GTS-21),and inhibitor group(HFD+cold stimulation+α7 nAChR inhibitor α-bungarotoxin).Interventions lasted for 4 weeks.Serum levels of total cho-lesterol(TG),triglyceride(TC)and free fatty acid(FFA),and the levels of tumor necrosis factor-α(TNF-α),interleu-kin-1β(IL-1β),IL-10,Toll-like receptor 4(TLR4),nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),transforming growth factor-β(TGF-β),cyclic adenosine monophosphate(cAMP)and norepinephrine(NE)in while adipose tissues were measured using ELISA.Hematoxylin-eosin(HE)staining was performed to observe morpho-logical changes in white adipose tissues.The mRNA levels of nitric oxide synthase 2(NOS2),arginase 1(Arg1),uncou-pling protein 1(UCP1),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)and PR domain-containing 16(PRDM16)in white adipose tissues were determine by RT-qPCR.Immunohistochemistry was employed to examine the expression levels of CD86,CD206,C/EBP homologous protein(CHOP),immunoglobulin heavy-chain binding protein(BiP)and UCP1.Western blot analysis was conducted to detect the protein levels of CHOP,BiP,UCP1,α7 nAChR,nu-clear factor-κB(NF-κB)p65,phosphorylated Janus kinase 2(p-JAK2)and phosphorylated signal transducer and activa-tor of transcription 3(p-STAT3)in white adipose tissues.RESULTS:Activation of α7 nAChR with GTS-21,combined with cold-induced thermogenesis,led to decreased levels of TC,TG and FFA in peripheral blood and reduced lipid droplet area in white adipose tissues.Additionally,α7 nAChR activation resulted in decreased expression of TLR4 and NLRP3.In white adipose tissue,there was an increase in Arg1 mRNA level and CD206 expression,while NOS2 mRNA level and CD86 expression decreased.Phosphorylation of the JAK2/STAT3 pathway was up-regulated,and NF-κB p65 level de-creased.The levels of pro-inflammatory cytokines TNF-α and IL-1β were reduced,whereas the levels of anti-inflammatory factors TGF-β and IL-10 increased.Expression of CHOP and BiP also declined.Furthermore,α7 nAChR activation in-creased the mRNA levels of PRDM16 and PGC-1α,as well as UCP1 expression in white adipose tissues.CONCLUSION:Activation of α7 nAChR combined with cold stimulation not only promotes the beiging of white adipose tissue in obese mice,but also alliviates metabolic disorders,thereby enhancing the thermogenic efficiency of white adipose tissue beiging.

Objective:To investigate the external quality control assessment results of iodine deficiency disorders (IDD) laboratories at all levels in Yunnan Province, so as to provide technical support for IDD monitoring.Methods:In 2023, all IDD laboratories at provincial, city (prefecture) and county level in Yunnan Province tested the assessment samples randomly provided by the National IDD Reference Laboratory based on their participation in external quality control assessment projects (urinary iodine, salt iodine, water iodine). For laboratories that do not use fully automatic iodine detectors, urinary iodine detection was carried out using the "Determination of Iodine in Urine - Part 1: As 3+-Ce 4+ Catalytic Spectrophotometry" (WS/T 107.1-2016), salt iodine detection was carried out using the direct titration method in the "General Test Methods in Salt Industry-Determination of Iodine"(GB/T 13025.7-2012), and water iodine detection was carried out using the cerium sulfate catalytic spectrophotometry. The test results were evaluated using standard value ± uncertainty. Results:A total of 146 IDD laboratories in Yunnan Province participated in the external quality control assessment, including 1 at the provincial level, 16 at the city (prefecture) level, and 129 at the county level. The feedback rate and qualification rate of urinary iodine, salt iodine in the provincial, city (prefecture) and county level IDD laboratories were all 100% (146/146). The feedback rate and the qualified rate of urinary iodine, salt iodine and water iodine in county level IDD laboratories were all 100%(17/17).Conclusion:In 2023, all external quality control assessment results of IDD laboratories in Yunnan Province are qualified, with stable testing quality, providing reliable laboratory technical support for IDD monitoring.

AIM:To explore the mechanism by which activation of α7 nicotinic acetylcholine receptor(nAChR)in combination with cold stimulation promotes the beiging of white adipose tissues in obese mice.METHODS:Male C57BL/6J mice,aged 8 weeks,were acclimated for 1 week before fed with high-fat diet(HFD)for 12 weeks to estab-lish an obese model.Fifty mice were randomly divided into 5 groups:control group(low-fat diet),HFD group,model group(HFD+cold stimulation),agonist group(HFD+cold stimulation+α7 nAChR agonist GTS-21),and inhibitor group(HFD+cold stimulation+α7 nAChR inhibitor α-bungarotoxin).Interventions lasted for 4 weeks.Serum levels of total cho-lesterol(TG),triglyceride(TC)and free fatty acid(FFA),and the levels of tumor necrosis factor-α(TNF-α),interleu-kin-1β(IL-1β),IL-10,Toll-like receptor 4(TLR4),nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),transforming growth factor-β(TGF-β),cyclic adenosine monophosphate(cAMP)and norepinephrine(NE)in while adipose tissues were measured using ELISA.Hematoxylin-eosin(HE)staining was performed to observe morpho-logical changes in white adipose tissues.The mRNA levels of nitric oxide synthase 2(NOS2),arginase 1(Arg1),uncou-pling protein 1(UCP1),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)and PR domain-containing 16(PRDM16)in white adipose tissues were determine by RT-qPCR.Immunohistochemistry was employed to examine the expression levels of CD86,CD206,C/EBP homologous protein(CHOP),immunoglobulin heavy-chain binding protein(BiP)and UCP1.Western blot analysis was conducted to detect the protein levels of CHOP,BiP,UCP1,α7 nAChR,nu-clear factor-κB(NF-κB)p65,phosphorylated Janus kinase 2(p-JAK2)and phosphorylated signal transducer and activa-tor of transcription 3(p-STAT3)in white adipose tissues.RESULTS:Activation of α7 nAChR with GTS-21,combined with cold-induced thermogenesis,led to decreased levels of TC,TG and FFA in peripheral blood and reduced lipid droplet area in white adipose tissues.Additionally,α7 nAChR activation resulted in decreased expression of TLR4 and NLRP3.In white adipose tissue,there was an increase in Arg1 mRNA level and CD206 expression,while NOS2 mRNA level and CD86 expression decreased.Phosphorylation of the JAK2/STAT3 pathway was up-regulated,and NF-κB p65 level de-creased.The levels of pro-inflammatory cytokines TNF-α and IL-1β were reduced,whereas the levels of anti-inflammatory factors TGF-β and IL-10 increased.Expression of CHOP and BiP also declined.Furthermore,α7 nAChR activation in-creased the mRNA levels of PRDM16 and PGC-1α,as well as UCP1 expression in white adipose tissues.CONCLUSION:Activation of α7 nAChR combined with cold stimulation not only promotes the beiging of white adipose tissue in obese mice,but also alliviates metabolic disorders,thereby enhancing the thermogenic efficiency of white adipose tissue beiging.

Objective:To explore the therapeutic efficacy and prognostic factors of combined rituximab and intensive chemotherapy for sporadic adult Burkitt lymphoma (BL) .Methods:This retrospective study examined the clinical and survival data of 30 patients newly diagnosed with BL between July 2011 and February 2023 at the Blood Diseases Hospital. Kaplan-Meier method was used for survival analysis, and the log-rank test was used for univariate analysis of prognostic factors.Results:The median age of the 30 patients was 43 years (24 - 66 years), and the male to female ratio was 3: 2. Extranodal invasion was present in 80% of the patients, with involvement of the bone marrow in 53.3% and central nervous system in 10.0%. The Ann Arbor stage was Ⅲ and Ⅳ in 86.7%. According to the number of Burkitt Lymphoma International Prognostic Index (BL-IPI) risk factors, patients were classified as low risk (0) in 20.0%, intermediate risk (1) in 43.3%, and high risk (≥2) in 36.7%. All patients were treated with an induction regimen of rituximab combined with intensive chemotherapy, with objective and complete response rates of 80.0% and 76.7%, respectively. The median follow-up was 49 months (6-153 months), and the 5-year progression-free survival (PFS) and overall survival (OS) rates were both (76.7±7.7) %. All patients with limited stage ( n=4) achieved continuous complete remission (CCR). Patients who had high risk, advanced stage sensitive to induction therapy ( n=10) sequentially received first-line autologous hematopoietic stem cell transplantation (auto-HSCT) as consolidation therapy; 9 patients achieved CCR, whereas 1 patient with central nervous system invasion developed early disease progression and died. The BL-IPI low, intermediate, and high risk groups had respective 5-year PFS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0069) and OS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0075). The main adverse effects of induction therapy were myelosuppression and secondary infections, which were effectively managed by appropriate symptomatic treatment. Univariate analysis demonstrated that worse PFS was associated with BL-IPI score ≥2 ( HR=4.90, 95% CI 1.02-23.45, P=0.0329) ; extranodal invasion at ≥2 sites ( HR=12.62, 95% CI 2.59-61.62, P=0.0021) ; and failure to achieve first complete response (CR1) after induction therapy ( HR=31.86, 95% CI 4.19-242.20, P<0.0001) . Conclusions:Intensive immunochemotherapy regimens were effective and well-tolerated by adult patients with highly aggressive BL. Treatment efficacy was ideal in patients with limited-stage disease, whereas prognosis was unsatisfactory in patients with high-risk BL-IPI. Sequential first-line auto-HSCT consolidation therapy may further improve outcomes in patients with high-risk advanced-stage disease who are sensitive to induction therapy. BL-IPI score ≥2, extranodal invasion at ≥2 sites, and failure to achieve CR1 after induction therapy were adverse prognostic factors in adult patients with BL.

Objective:To investigate the clinical subtypes of acute aortic dissection (AAD) through latent class analysis.Methods:This study was a multicenter retrospective cohort study. Patients with AAD admitted to five hospitals, including Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Henan Provincial People′s Hospital, Central China Fuwai Hospital of Zhengzhou University (Fuwai Central China Cardiovascular Hospital), the Third Affiliated Hospital of Xinxiang Medical University and the Second Affiliated Hospital of Chongqing Medical University, between August 2010 and December 2021 were enrolled. Based on clinical and biological characteristics, latent class analysis (models with 2 to 5 latent classes) was conducted to classify the enrolled patients. The optimal classification scheme was determined using model fitting evaluations, including log-likelihood (LL), entropy, Lo-Mendell-Rubin adjusted likelihood ratio test and so on. Clinical data of different subtypes were compared, and in-hospital mortality was analyzed across the entire population and among subgroups receiving different treatments.Results:A total of 2 689 AAD patients, aged 54 (46, 63) years were included, with 1 305 (48.5%) having DeBakey type Ⅰ, 156 (5.8%) type Ⅱ, and 1 228 (45. 7%) type Ⅲ dissections. The cohort comprised 2 134 (79.4%) males. The overall in-hospital mortality rate was 22.8% (613/2 689). Latent class analysis indicated that a two-class model was optimal (LL=147 413.242, entropy=0.812, and PLMRT<0.001). Patients were classified into two subtypes, named clinical subtype 1 and clinical subtype 2. Compared to clinical subtype 1, clinical subtype 2 had a higher proportion of females, was older, had more dissections involving the ascending aorta, and exhibited higher rates of organ dysfunction (elevated alanine aminotransferase and creatinine levels) and inflammatory response (neutrophilia) (all P<0.05). Clinical subtype 2 also showed higher in-hospital mortality compared to subtype 1 (26.3% (238/905) vs. 21.0% (375/1 784), P=0.002). Among patients undergoing surgical treatment, clinical subtype 2 had higher mortality than subtype 1 (40.1% (67/167) vs. 30.0% (101/337), P=0.027). However, no significant differences in mortality were observed between the two subtypes among patients receiving medical therapy or endovascular and hybrid procedures (all P>0.05). Conclusions:Comprehensive latent class analysis identifies two subtypes of AAD with distinct clinical characteristics and treatment responses. These findings provide new insights into individualized clinical decision-making and prognostic evaluation for AAD patients.

【Objective】 To evaluate the clinical implications of ARL5B in esophageal cancer and its underlying mechanisms by using bioinformatics methods. 【Methods】 ARL5B transcriptomic expression data were obtained from The Cancer Genome Atlas (TCGA), R software was employed to detect the differential expression mRNAs, and related clinical information was collected for survival analysis. To validate the bioinformatics results, Real-time quantitative PCR (qRT-PCR) and Western blotting were carried out for clinical specimens of esophageal cancer tumor tissues and adjacent tissues. Immunohistochemistry was used to evaluate the expression of ARL5B and its associated clinicopathologic features. The underlying mechanisms of ARL5B in esophageal cancer were preliminarily explored by bioinformatics and qRT-PCR. 【Results】 Bioinformatics method showed that the expression of ARL5B in human esophageal cancer tissues was significantly higher than in adjacent tissues and correlated with poor prognosis. Clinical specimens were detected, the expressions of ARL5B mRNA and protein were the highest in metastases lymph node, followed by esophageal cancer tissues and adjacent tissues, which corresponded with bioinformatics results. The expression of ARL5B was strongly correlated with lymph node metastases and advanced clinical stage. Kaplan-Meier analysis results denoted high ARL5B level, indicating poor prognosis. Enrichment analysis showed that ARL5B was associated the biological processes such as vacuolar transport, late endosome to lysosome transport, and organelle localization. Protein-protein interaction analysis (PPI) suggested that ARL5B might interact with VPS16, KIF1A and TOM1, whose expressions were verified by qRT-PCR and positively correlated with ARL5B expression. 【Conclusion】 ARL5B was highly expressed in esophageal cancer and associated with lymph node metastases, advanced clinical stage, and poor prognosis. ARL5B may be involved in the progression of esophageal cancer with several molecular mechanisms.