Objective:To examine the clinical features and genetic profiles of patients with thyroid peroxidase(TPO) gene mutations and provide diagnostic guidance for clinicians.Methods:A retrospective review of four patients with TPO mutations treated at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from January 2014 to December 2023. Data on demographics, clinical manifestation, genotypes, treatment, and prognosis of these patients were analyzed.Results:Two males and two females, aged 13 to 27 years at diagnosis, presented with goiter as the initial symptom, with three cases menifesting during puberty. Laboratory findings showed mildly elevated or upper-limit-normal serum thyroid-stimulating hormone(TSH) levels, significantly increased free triiodothyronine/free thyroxine(FT 3/FT 4) ratios, and elevated thyroglobulin(TG) levels. Genetic testing revealed compound heterozygous pathogenic or likely pathogenic TPO mutations. Despite regular levothyroxine(L-T 4) therapy, goiter persisted. Three patients required thyroidectomy due to cosmetic or compressive symptoms, with pathology showing follicular hyperplasia. Conclusion:TPO mutations are characterized by adolescent-onset goiter, elevated FT 3/FT 4 ratios, and normal to high TSH. Genetic testing confirms the diagnosis. L-T 4 offers limited improvement, and surgery is often needed.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

BACKGROUND:Studies have confirmed that up-regulation of microRNA-140 expression can partially inhibit osteoarthritis-like changes in knee cartilage tissues and cells and delay the progression of osteoarthritis,suggesting that microRNA-140 is involved in the pathogenesis of osteoarthritis.OBJECTIVE:To further analyze the mechanism of microRNA-140 involvement in osteoarthritis by loading exosomes overexpressing microRNA-140 with sodium alginate/collagen hydrogel.METHODS:Lentivirus was used to infect rat bone marrow mesenchymal stem cells to overexpress microRNA-140,then exosomes were isolated and exosomes overexpressing microRNA-140 were obtained.Sodium alginate/collagen hydrogels loaded with exosomes were prepared.Thirty-two SD rats were randomly divided into four groups,with 8 rats in each group.Normal control group did not receive any treatment.The osteoarthritis model was established by injecting sodium iodoacetate into the knee cavity in the osteoarthritis group,the non-transfected exosome group and the transfected exosome group.Two weeks later,PBS was injected into the knee cavity in the osteoarthritis group.Sodium alginate/collagen hydrogel carrying non-overexpressing microRNA-140 and overexpressing microRNA-140 exosomes were injected into the knee cavity of the non-transfected exosome group and transfected exosome group.At 6 weeks after modeling,the threshold of mechanical foot withdrawal response,the concentration of inflammatory factors in synovial fluid,the expression of chondrogen-related genes,the histological changes of knee cartilage and the expression of pyroptosis related proteins were detected in rats.RESULTS AND CONCLUSION:(1)Compared with normal control group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and Type Ⅱ collagen immunofluorescence intensity were decreased in the osteoarthritis group(P<0.05),and proinflammatory cytokine levels were increased in synovial fluid(P<0.05).The mRNA expressions of matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS-5)were increased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were increased(P<0.05).Immunofluorescence intensity of GSDMD and cleaved caspase-1 was increased(P<0.05),and cartilage tissue was severely damaged.(2)Compared with osteoarthritis group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and type Ⅱ collagen immunofluorescence intensity in the non-transfected and transfected exosome groups were increased(P<0.05);proinflammatory cytokine levels were decreased in synovial fluid(P<0.05).The mRNA expression of matrix metalloproteinase 13 was decreased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were decreased(P<0.05).The immunofluorescence intensity of GSDMD and cleaved caspase-1 decreased(P<0.05),and the cartilage tissue damage was reduced(P<0.05),and the effect was stronger in the transfected exosome group.(3)These results conclude that microRNA-140 can reduce the pain response of rats with osteoarthritis by inhibiting inflammation,maintaining cartilage homeostasis,and inhibiting cartilaginous pyroptosis,thereby reducing cartilage damage and playing a therapeutic role in osteoarthritis.

BACKGROUND:Studies have confirmed that up-regulation of microRNA-140 expression can partially inhibit osteoarthritis-like changes in knee cartilage tissues and cells and delay the progression of osteoarthritis,suggesting that microRNA-140 is involved in the pathogenesis of osteoarthritis.OBJECTIVE:To further analyze the mechanism of microRNA-140 involvement in osteoarthritis by loading exosomes overexpressing microRNA-140 with sodium alginate/collagen hydrogel.METHODS:Lentivirus was used to infect rat bone marrow mesenchymal stem cells to overexpress microRNA-140,then exosomes were isolated and exosomes overexpressing microRNA-140 were obtained.Sodium alginate/collagen hydrogels loaded with exosomes were prepared.Thirty-two SD rats were randomly divided into four groups,with 8 rats in each group.Normal control group did not receive any treatment.The osteoarthritis model was established by injecting sodium iodoacetate into the knee cavity in the osteoarthritis group,the non-transfected exosome group and the transfected exosome group.Two weeks later,PBS was injected into the knee cavity in the osteoarthritis group.Sodium alginate/collagen hydrogel carrying non-overexpressing microRNA-140 and overexpressing microRNA-140 exosomes were injected into the knee cavity of the non-transfected exosome group and transfected exosome group.At 6 weeks after modeling,the threshold of mechanical foot withdrawal response,the concentration of inflammatory factors in synovial fluid,the expression of chondrogen-related genes,the histological changes of knee cartilage and the expression of pyroptosis related proteins were detected in rats.RESULTS AND CONCLUSION:(1)Compared with normal control group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and Type Ⅱ collagen immunofluorescence intensity were decreased in the osteoarthritis group(P<0.05),and proinflammatory cytokine levels were increased in synovial fluid(P<0.05).The mRNA expressions of matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMTS-5)were increased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were increased(P<0.05).Immunofluorescence intensity of GSDMD and cleaved caspase-1 was increased(P<0.05),and cartilage tissue was severely damaged.(2)Compared with osteoarthritis group,the threshold value of mechanical stimulation foot contraction response,type Ⅱ collagen,SOX9 mRNA expression levels,and type Ⅱ collagen immunofluorescence intensity in the non-transfected and transfected exosome groups were increased(P<0.05);proinflammatory cytokine levels were decreased in synovial fluid(P<0.05).The mRNA expression of matrix metalloproteinase 13 was decreased(P<0.05),and the protein expression levels of NLRP3,ASC,GSDMD p30,caspase-1 p20,interleukin-1β,and interleukin-18 were decreased(P<0.05).The immunofluorescence intensity of GSDMD and cleaved caspase-1 decreased(P<0.05),and the cartilage tissue damage was reduced(P<0.05),and the effect was stronger in the transfected exosome group.(3)These results conclude that microRNA-140 can reduce the pain response of rats with osteoarthritis by inhibiting inflammation,maintaining cartilage homeostasis,and inhibiting cartilaginous pyroptosis,thereby reducing cartilage damage and playing a therapeutic role in osteoarthritis.

Objective:To examine the clinical features and genetic profiles of patients with thyroid peroxidase(TPO) gene mutations and provide diagnostic guidance for clinicians.Methods:A retrospective review of four patients with TPO mutations treated at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from January 2014 to December 2023. Data on demographics, clinical manifestation, genotypes, treatment, and prognosis of these patients were analyzed.Results:Two males and two females, aged 13 to 27 years at diagnosis, presented with goiter as the initial symptom, with three cases menifesting during puberty. Laboratory findings showed mildly elevated or upper-limit-normal serum thyroid-stimulating hormone(TSH) levels, significantly increased free triiodothyronine/free thyroxine(FT 3/FT 4) ratios, and elevated thyroglobulin(TG) levels. Genetic testing revealed compound heterozygous pathogenic or likely pathogenic TPO mutations. Despite regular levothyroxine(L-T 4) therapy, goiter persisted. Three patients required thyroidectomy due to cosmetic or compressive symptoms, with pathology showing follicular hyperplasia. Conclusion:TPO mutations are characterized by adolescent-onset goiter, elevated FT 3/FT 4 ratios, and normal to high TSH. Genetic testing confirms the diagnosis. L-T 4 offers limited improvement, and surgery is often needed.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

OBJECTIVE To explore the intestinal absorption characteristics of saikosaponins. METHODS Based on everted intestinal sac model， using accumulative absorption amount （Q） and absorption rate constant （Ka） as indexes， UHPLC-MS/MS technique as a method， the absorption of saikosaponin A， B2， C， D and F from total saponins of Bupleurum chinense （8 g/mL， by crude drug） in the duodenum， jejunum and ileum was detected. RESULTS The correlation coefficients （r） of the regression equations for the absorption of saikosaponins A， B2， C and F in the duodenum， jejunum and ileum were all higher than 0.95， while the r of saikosaponin D in the above intestinal segments was lower than 0.95； compared with the absorption of the same composition in the duodenum， the Q and Ka of saikosaponin A and C circulating in jejunum and ileum for 120 min， as well as the Q and Ka of saikosaponin F circulating in the ileum for 120 min were significantly decreased （P＜0.05）. CONCLUSIONS Saikosaponin A and the other 4 saikosaponins are all absorbed in the duodenum， jejunum and ileum； among them， saikosaponin A， B2， C and F are linearly absorbed， which conforms to the zero-order absorption characteristics， but saikosaponin D shows non- linear absorption.

Objective:To investigate the relationship between single nucleotide polymorphism (SNPs) of Zeste homolog enhancer 2 (EZH2) gene and the risk of breast cancer.Methods:Recruiting 1 039 breast cancer patients and 1 040 controls at 22 referral hospitals nationwide in China, the genotype distribution of 3 SNPs loci of EZH2 genes was observed to detect the correlation between different genotypes and the risk of breast cancer genotypes EZH2 expression in breast cancer tissues and its correlation with patient prognosis were analyzed using breast cancer data from the database.Results:EZH2 rs6464926 CC genotype was compared with TT genotype (TT vs. CC: OR=1.362, 95% CI: 1.063-1.746, P=0.015) and dominant model (TC+TT vs .CC: OR=1.22, 95% CI: 1.004-1.483, P=0.045) .In women with BMI ≥24 kg/m 2, the TC genotype ( P=0.050), TT genotype ( P=0.025) and dominant model (TC+TT, P=0.021) of rs6464926 locus were significantly different from CC genotype in cancer risk. rs6464926 was correlated with EZH2 gene expression ( P=6.89E-47). EZH2 gene is highly expressed in breast cancer tissues, and patients with high expression were associated with shorter OS ( HR=1.27, P=0.013), DMFS ( HR=1.37, P<0.01), and RFS ( HR=1.44, P<0.01). Conclusions:The polymorphism rs6464926 of EZH2 gene is associated with breast cancer susceptibility in Chinese women. rs6464926 might regulate breast cancer risk and prognosis by changing EZH2 expression.

Objective To explore the expression of heat shock protein (HSP) 105b in advanced adenocarcinoma of esophagogastric junction (AEG) patients and its relation with clinicopathological characteristics and effect of hyperthermic intraperitoneal chemotherapy (HIPEC). Methods We randomly divided 166 cases of advanced AEG who underwent open radical gastrectomy and lymphadenectomy D2 compartment into treatment group (prophylactic HIPEC of paclitaxel after operation) and control group (conventional treatment). Immunohistochemistry was used to detect HSP105b expression in postoperative tumor tissues, and to analyze its relation with clinicopathological characteristics and effect of HIPEC. Results The expression of HSP105b was only associated with tumor vein infiltration (t=4.002, P=0.045). The 3-year disease-free survival rate of the patients with high HSP105b expression was significantly lower than those with low HSP105b expression (56.5% vs. 64.8%, χ²=35.508, P < 0.001), and the disease-free survival rate of the patients with high HSP105b expression in treatment group was significantly lower than that with low HSP105b expression (60.7% vs. 71.5%, χ²=77.459, P < 0.001). Conclusion HSP105b can be used as a prognostic factor and its expression can predict the efficacy of HIPEC in the patients with advanced AEG.

Objective To analyze the serum miRNA expression levels in non-obstructive azoospermia (NOA) patients and healthy sperm donors.Methods Serum miRNA levels in NOA patients and healthy sperm donors were analyzed by adopting the miRNA expression profiles chip.The data were processed and an alyzed by using the GenePix proV6.0 software to find out the differentially expressed miRNA,then the difference was verified by RQ-PCR,finally the bioinformatic software was utilized to predict the miRNA target gene.Results Compared to healthy sperm donors,71 cases of NOA had miRNAs expression difference,miRNA expression were increased in 47 cases and miRNAs expression was decreased in 24 cases.Moreover,Realtime PCR analysis verified the chip accuracy.The bioinformatic software target gene prediction showed that the potential target gene of these differential miRNA were involved in spermatogenesis.Conclusion The specific miRNA exists in serum miRNA of NOA,which helps to study the molecular mechanism of spermatogenesis.