Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.

BACKGROUND:Mechanical alignment is the"gold standard"alignment technique in total knee arthroplasty,but regardless of advances in prosthetic materials and robotic-assisted navigation,mechanical alignment-total knee arthroplasty still has a patient dissatisfaction rate of about 20％.OBJECTIVE:To evaluate the early efficacy of navigation-assisted total knee arthroplasty using functional alignment.METHODS:A total of 44 consecutive cases(50 knees)that underwent computer navigation-assisted total knee arthroplasty with functional alignment from October 2019 to June 2023 were retrospectively analyzed,including 12 males(14 knees)and 32 females(36 knees).A total of 46 consecutive cases(50 knees)that underwent navigation-assisted total knee arthroplasty with mechanical axis alignment by the same surgical team during the same period were selected as controls,including 5 males(5 knees)and 41 females(45 knees).The tibial osteotomy angle,tibial plateau osteotomy amount,femoral osteotomy angle,distal femoral,posterior and anterior osteotomy amount,and joint line movement were observed in the two groups of patients.Preoperative and postoperative flexion and extension gap internal and external laxity,hip-knee-ankle angle,mechanical lateral distal femoral angle,mechanical medial proximal tibial angle,joint line convergence angle,sagittal femoral component angle,posterior tibial slope,arithmetic hip-knee-ankle angle,joint line obliquity,coronal plane alignment of the knee classification,Western Ontario and McMaster Universities Osteoarthritis Index,and Hospital for Special Surgery score and forgotten joint score were compared between the two groups.RESULTS AND CONCLUSION:(1)The intraoperative tibial plateau osteotomy angle in the functional alignment group was greater than that in the mechanical axis alignment group,and the proportion of gap imbalance(2％)was smaller than that in the mechanical axis alignment group(18％).The differences were all significant(P＜0.05).(2)The hip-knee-ankle angle,mechanical medial proximal tibial angle,arithmetic hip-knee-ankle angle,and joint line obliquity in the functional alignment group were smaller than those in the mechanical axis alignment group postoperatively,and the differences were significant(P＜0.05).(3)The most common coronal plane alignment of the knee classification before surgery was type Ⅰ(80％in the functional alignment group and 42％in the mechanical axis alignment group).(4)The proportion of joint line obliquity＜177°(44％)in the functional alignment group was greater than that in the mechanical axis alignment group(14％)postoperatively.(5)Hospital for Special Surgery score at 1 month,6 months,and last follow-up after surgery was higher in the functional alignment group than that in the mechanical axis alignment group;the differences were statistically significant(P＜0.05).The Western Ontario and McMaster Universities Osteoarthritis Index 1 month after surgery was lower in the functional alignment group than that in the mechanical axis alignment group;the difference was statistically significant(t=-2.85,P=0.005).There was no significant difference in postoperative range of motion and forgotten joint score between the two groups(P＞0.05).(6)It is indicated that navigation-assisted total knee arthroplasty using functional alignment optimizes early clinical efficacy.The functional alignment technique has advantages in restoration of constitutional alignment and joint line obliquity and avoids soft tissue release compared to mechanical alignment technique.

Colorectal cancer (CRC) is one of the most malignant tumors with high morbidity and mortality worldwide. Early diagnosis and accurate pathological evaluation are of great significance for improving patient prognosis. Endoscopic resection is the main treatment for early CRC. Pathological parameters-such as margin status, lymphatic vascular invasion (LVI), tumor grade, depth of submucosal invasion and tumor budding are the key to determine whether curative resection is achieved. At present, the measurement method of submucosal invasion depth of pT1 CRC is controversial. Submucosal invasion depth measurement adopts different measurement methods for pedunculated and sessile lesions, mainly including measurement from the surface of the lesion or the lower edge of the mucosal muscle layer. Especially for sessile lesions, due to different observers different understandings of the position of the mucosal muscle layer that can be identified or evaluated in the guidelines, observers may apply different criteria to evaluate the integrity of the mucosal muscle layer. In recent years, more and more evidence has shown that the association between the depth of submucosal invasion and the risk of lymph node metastasis may be overestimated, while other pathological parameters (such as LVI, high-grade tumor budding, and poorly differentiated components) have equal or more important significance in prognostic stratification. Therefore, the current measurement of the depth of submucosal invasion of pT1 CRC and its prognostic value are facing challenges, which deserve our attention and further exploration.

Objective To investigate the correlation between G protein-coupled receptor family C group 6 member A(GPRC6A)gene polymorphisms and their expression and pulmonary infections in elderly patients with chronic heart failure(CHF).Methods 138 elderly CHF patients admitted to the Xianyang First People's Hospital from January 2021 to January 2024 were selected as the research subjects,and were divided into an infected group(n=42)and an uninfected group(n=96)based on their lung infection status.Polymerase chain reaction(PCR)was used to detect polymorphisms at the rs6901250 and rs1606365 loci of the GPRC6A gene.The allele and genotype frequency distributions of the infected and uninfected groups were compared.Logistic regression modeling was used to analyze the s6901250 and rs1606365 loci under three genetic models(co-dominant,dominant and reces-sive)and lung infections in elderly patients with CHF.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression level of GPRC6A gene.The predictive value of the mRNA expression level of the GPRC6A gene for the development of pulmonary infections in elderly patients with CHF was analyzed by applying the receiver operator characteristic(ROC)curve.Results The distribution of genotypes at loci rs6901250 and rs1606365 of the GPRC6A gene in both the infected and uninfected groups of the lungs of elderly CHF patients conformed to the Hardy-Weinberg equilibrium law(χ2=0.199～0.376,all P>0.05),which was representative of the population.Compared with the uninfected group,the frequency of allele A at locus rs6901250(57.14%vs 41.67%)was significantly higher in the infected group,Allele G(54.76%vs.37.50%)and genotype GG(14.06%vs 29.99%)frequencies were significantly higher at locus rs1606365,and the differences were statistically significant(χ2=5.628,7.114,6.849,all P<0.05).At locus rs6901250,in the co-dominant model(GG vs AA)and the dominant model(GA+AA vs GG),the elderly CHF patients with AA genotype the risk of lung infection was higher than that of GG genotype(OR=1.753,1.546,all P<0.05);.rs1606365 locus showed that the risk of lung infection was higher than that of CC genotype in el-derly CHF patients with GG genotype under all three genetic models of co-dominant model(CC vs GG),dominant model(CG+GG vs CC)and recessive model(CG+CC vs GG)(OR=1.833,1.741,0.695,all P<0.05).The mRNA expression level of GPR-C6A gene in the lung-infected group of elderly CHF patients(1.43±0.35)was significantly higher than that in the uninfected group(1.02±0.21),and the difference was statistically significant(t=8.515,P<0.001).The results of the ROC curve analysis showed that the GPRC6A gene expression level predicted lung infection in elderly CHF patients with an AUC value of 0.895,a cut-offvalue of 1.37,and sensitivity and specificity of 85.7%and 66.7%,respectively.Conclusion The AA genotype at the rs6901250 locus and the GG genotype at the rs1606365 locus of the GPRC6A gene increased the risk of developing lung infec-tions in elderly patients with CHF.MRNA expression levels of the GPRC6A gene were elevated in the infected group,and its ex-pression level could be used as a predictive indicator for the development of lung infections in elderly patients with CHF.

Phyllodes tumors (PT) of the breast is a rare fibroepithelial tumor, which can be divided into benign, borderline and malignant pathological types according to its histological characteristics. Malignant phyllodes tumor (MPT) accounts for 10%-20% of PT and has the ability of local recurrence and distant metastasis. Therefore, accurate diagnosis and identification of MPT are particularly important for patients to obtain appropriate treatment at the initial diagnosis. At present, histological morphology is the only diagnostic basis for MPT. However, due to the fact that phyllode tumor itself is a continuous disease spectrum with overlapping histological features, and the diagnostic classification adopts many histological parameters and their evaluation is subjective, pathologists lack consistency in MPT grading, and the biological behavior of PT is not completely consistent. Therefore, the existing MPT classification standards are facing challenges, and the accurate and reproducible classification is worthy of further exploration.

Objective To investigate the correlation between G protein-coupled receptor family C group 6 member A(GPRC6A)gene polymorphisms and their expression and pulmonary infections in elderly patients with chronic heart failure(CHF).Methods 138 elderly CHF patients admitted to the Xianyang First People's Hospital from January 2021 to January 2024 were selected as the research subjects,and were divided into an infected group(n=42)and an uninfected group(n=96)based on their lung infection status.Polymerase chain reaction(PCR)was used to detect polymorphisms at the rs6901250 and rs1606365 loci of the GPRC6A gene.The allele and genotype frequency distributions of the infected and uninfected groups were compared.Logistic regression modeling was used to analyze the s6901250 and rs1606365 loci under three genetic models(co-dominant,dominant and reces-sive)and lung infections in elderly patients with CHF.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression level of GPRC6A gene.The predictive value of the mRNA expression level of the GPRC6A gene for the development of pulmonary infections in elderly patients with CHF was analyzed by applying the receiver operator characteristic(ROC)curve.Results The distribution of genotypes at loci rs6901250 and rs1606365 of the GPRC6A gene in both the infected and uninfected groups of the lungs of elderly CHF patients conformed to the Hardy-Weinberg equilibrium law(χ2=0.199～0.376,all P>0.05),which was representative of the population.Compared with the uninfected group,the frequency of allele A at locus rs6901250(57.14%vs 41.67%)was significantly higher in the infected group,Allele G(54.76%vs.37.50%)and genotype GG(14.06%vs 29.99%)frequencies were significantly higher at locus rs1606365,and the differences were statistically significant(χ2=5.628,7.114,6.849,all P<0.05).At locus rs6901250,in the co-dominant model(GG vs AA)and the dominant model(GA+AA vs GG),the elderly CHF patients with AA genotype the risk of lung infection was higher than that of GG genotype(OR=1.753,1.546,all P<0.05);.rs1606365 locus showed that the risk of lung infection was higher than that of CC genotype in el-derly CHF patients with GG genotype under all three genetic models of co-dominant model(CC vs GG),dominant model(CG+GG vs CC)and recessive model(CG+CC vs GG)(OR=1.833,1.741,0.695,all P<0.05).The mRNA expression level of GPR-C6A gene in the lung-infected group of elderly CHF patients(1.43±0.35)was significantly higher than that in the uninfected group(1.02±0.21),and the difference was statistically significant(t=8.515,P<0.001).The results of the ROC curve analysis showed that the GPRC6A gene expression level predicted lung infection in elderly CHF patients with an AUC value of 0.895,a cut-offvalue of 1.37,and sensitivity and specificity of 85.7%and 66.7%,respectively.Conclusion The AA genotype at the rs6901250 locus and the GG genotype at the rs1606365 locus of the GPRC6A gene increased the risk of developing lung infec-tions in elderly patients with CHF.MRNA expression levels of the GPRC6A gene were elevated in the infected group,and its ex-pression level could be used as a predictive indicator for the development of lung infections in elderly patients with CHF.

Phyllodes tumors (PT) of the breast is a rare fibroepithelial tumor, which can be divided into benign, borderline and malignant pathological types according to its histological characteristics. Malignant phyllodes tumor (MPT) accounts for 10%-20% of PT and has the ability of local recurrence and distant metastasis. Therefore, accurate diagnosis and identification of MPT are particularly important for patients to obtain appropriate treatment at the initial diagnosis. At present, histological morphology is the only diagnostic basis for MPT. However, due to the fact that phyllode tumor itself is a continuous disease spectrum with overlapping histological features, and the diagnostic classification adopts many histological parameters and their evaluation is subjective, pathologists lack consistency in MPT grading, and the biological behavior of PT is not completely consistent. Therefore, the existing MPT classification standards are facing challenges, and the accurate and reproducible classification is worthy of further exploration.

BACKGROUND:Mechanical alignment is the"gold standard"alignment technique in total knee arthroplasty,but regardless of advances in prosthetic materials and robotic-assisted navigation,mechanical alignment-total knee arthroplasty still has a patient dissatisfaction rate of about 20％.OBJECTIVE:To evaluate the early efficacy of navigation-assisted total knee arthroplasty using functional alignment.METHODS:A total of 44 consecutive cases(50 knees)that underwent computer navigation-assisted total knee arthroplasty with functional alignment from October 2019 to June 2023 were retrospectively analyzed,including 12 males(14 knees)and 32 females(36 knees).A total of 46 consecutive cases(50 knees)that underwent navigation-assisted total knee arthroplasty with mechanical axis alignment by the same surgical team during the same period were selected as controls,including 5 males(5 knees)and 41 females(45 knees).The tibial osteotomy angle,tibial plateau osteotomy amount,femoral osteotomy angle,distal femoral,posterior and anterior osteotomy amount,and joint line movement were observed in the two groups of patients.Preoperative and postoperative flexion and extension gap internal and external laxity,hip-knee-ankle angle,mechanical lateral distal femoral angle,mechanical medial proximal tibial angle,joint line convergence angle,sagittal femoral component angle,posterior tibial slope,arithmetic hip-knee-ankle angle,joint line obliquity,coronal plane alignment of the knee classification,Western Ontario and McMaster Universities Osteoarthritis Index,and Hospital for Special Surgery score and forgotten joint score were compared between the two groups.RESULTS AND CONCLUSION:(1)The intraoperative tibial plateau osteotomy angle in the functional alignment group was greater than that in the mechanical axis alignment group,and the proportion of gap imbalance(2％)was smaller than that in the mechanical axis alignment group(18％).The differences were all significant(P＜0.05).(2)The hip-knee-ankle angle,mechanical medial proximal tibial angle,arithmetic hip-knee-ankle angle,and joint line obliquity in the functional alignment group were smaller than those in the mechanical axis alignment group postoperatively,and the differences were significant(P＜0.05).(3)The most common coronal plane alignment of the knee classification before surgery was type Ⅰ(80％in the functional alignment group and 42％in the mechanical axis alignment group).(4)The proportion of joint line obliquity＜177°(44％)in the functional alignment group was greater than that in the mechanical axis alignment group(14％)postoperatively.(5)Hospital for Special Surgery score at 1 month,6 months,and last follow-up after surgery was higher in the functional alignment group than that in the mechanical axis alignment group;the differences were statistically significant(P＜0.05).The Western Ontario and McMaster Universities Osteoarthritis Index 1 month after surgery was lower in the functional alignment group than that in the mechanical axis alignment group;the difference was statistically significant(t=-2.85,P=0.005).There was no significant difference in postoperative range of motion and forgotten joint score between the two groups(P＞0.05).(6)It is indicated that navigation-assisted total knee arthroplasty using functional alignment optimizes early clinical efficacy.The functional alignment technique has advantages in restoration of constitutional alignment and joint line obliquity and avoids soft tissue release compared to mechanical alignment technique.

Objective:To investigate the efficacy and safety of bendamustine combined with anti-CD20 monoclonal antibody in the first-line treatment of older patients with indolent B-cell non-Hodgkin lymphoma (B-iNHL) .Methods:The clinical data of 159 patients with B-iNHL enrolled in 16 hospitals from Jiangsu Cooperative Lymphoma Group from December 1, 2019, to April 20, 2024, were analyzed for regimen efficacy and safety. Bendamustine plus rituximab (BR) and bendamustine plus obinutuzumab (BG) were administered to 139 (87.4% ) and 20 (12.6% ) patients, respectively.Results:Among the 159 patients, 101 (63.5% ) were male and 58 (36.5% ) were female, with a median age of 69 years (range: 60–84). Efficacy could be assessed in 138 (86.8% ) patients. The efficacy assessment demonstrated that the overall response rate was 92.0% with complete and partial remissions in 75 (54.3% ) and 52 (37.7% ) cases, respectively. With a median follow-up of 24 months (range: 4–64), the progression-free survival rate was (87.5 ± 3.0) % and the overall survival rate was (83.2 ± 3.3) %. Of the 27 patients who died, 6 (22.2% ) died due to disease progression. The mean applied dose of bendamustine per cycle was 73.0 (50.8–89.7) mg/m 2 per day, administered on days 1 and 2. Adverse events of grade 3 or higher were reported in 53 (33.3% ) patients, with infection (30 cases,18.9% ) and neutropenia (24 cases, 15.1% ) demonstrating the highest incidence. Conclusion:Bendamustine combined with anti-CD20 monoclonal antibody demonstrated good efficacy and is well-tolerated in the first-line treatment of elderly patients with B-iNHL.

Colorectal cancer (CRC) is one of the most malignant tumors with high morbidity and mortality worldwide. Early diagnosis and accurate pathological evaluation are of great significance for improving patient prognosis. Endoscopic resection is the main treatment for early CRC. Pathological parameters-such as margin status, lymphatic vascular invasion (LVI), tumor grade, depth of submucosal invasion and tumor budding are the key to determine whether curative resection is achieved. At present, the measurement method of submucosal invasion depth of pT1 CRC is controversial. Submucosal invasion depth measurement adopts different measurement methods for pedunculated and sessile lesions, mainly including measurement from the surface of the lesion or the lower edge of the mucosal muscle layer. Especially for sessile lesions, due to different observers different understandings of the position of the mucosal muscle layer that can be identified or evaluated in the guidelines, observers may apply different criteria to evaluate the integrity of the mucosal muscle layer. In recent years, more and more evidence has shown that the association between the depth of submucosal invasion and the risk of lymph node metastasis may be overestimated, while other pathological parameters (such as LVI, high-grade tumor budding, and poorly differentiated components) have equal or more important significance in prognostic stratification. Therefore, the current measurement of the depth of submucosal invasion of pT1 CRC and its prognostic value are facing challenges, which deserve our attention and further exploration.