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.

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.

Heat shock factor 1(HSF1)is a core transcription factor in cellular stress response and protein homeostasis maintenance,and is widely involved in biological processes such as cell growth,differentiation,and metabolism.This study aims to design antigenic peptides of the sheep HSF1 protein and prepare polyclonal antibodies through bioinformatics analysis and immunologi-cal techniques,and verify their application effects in sheep lung and testis tissues.Firstly,the se-quence,structure,and evolution of the sheep HSF1 gene were analyzed using bioinformatics meth-ods,and key antigenic epitopes were predicted.Then,suitable peptide fragments were selected for synthesis,emulsified with Freund's complete adjuvant or incomplete adjuvant,and used to immu-nize New Zealand rabbits.The specificity and effectiveness of the antibodies were verified by indi-rect ELISA,Western blot,and immunohistochemistry(IHC)experiments.The results showed that the HSF1 protein is 564 amino acids(aa)in length,with a molecular weight of 60.76 kDa,a theo-retical isoelectric point(pI)of 5.32,and is hydrophilic and unstable.Phylogenetic tree analysis revealed that HSF1 is highly conserved among most members of the Bovidae family,as well as in humans,mice,rats,and other species,but with local site differences.Sheep HSF1 is most closely related to goat HSF1,followed by Canadian bighorn sheep and goral.The phosphorylation sites of sheep HSF1 are predominantly concentrated in the middle and C-terminal regions,which is largely consistent with the predicted results for human HSF1,though some local differences exist.The prepared polyclonal antibodies exhibited a titer of over 1:8000 in recognizing the sheep HSF1 pro-tein,and Western blot experiments confirmed clear bands with consistent molecular weight,indica-ting high specificity of the antibodies.Furthermore,the expression and specific distribution of HSF1 were detected in sheep lung and testis tissues.This study successfully prepared polyclonal antibodies based on the sheep HSF1 antigen peptide and,for the first time,detected the immuno-histochemical distribution of HSF1 in the testis and lung tissues of Argali hybrid sheep.This pro-vides an important tool for further exploring the physiological role of HSF1 in Argali hybrid sheep and its potential applications in stress response,disease prevention,and treatment.

Mandibular reconstruction refers to the restoration of the continuity of the mandible through techniques such as autologous bone grafting,thereby restoring the patient's basic appearance,reconstructing the occlusal relationship,and restoring functions such as opening the mouth,chewing,and swallowing,in order to achieve a unity of oral and maxillofacial forms and functions.Due to the fact that mastication necessitates the coordinated efforts of the masticatory muscles,mandible,dental arch,and tongue,the recovery of masticatory function not only serves as a robust indicator for the success of surgery but also enhances the patients'quality of life,facilitating an early return to normal life.Currently,for the rehabilitation of oral function in patients after mandibular reconstruction surgery,standardized tools have been established in the fields of swallowing,occlusion,and speech assessment,and targeted training has been implemented,yielding significant therapeutic outcomes.However,research related to masticatory function faces two major challenges.First,existing assessment tools primarily focus on a single dimension,such as masticatory efficiency or subjective perception,and an integrated assessment system that encompasses multiple dimensions,including bite force distribution and oral sensory perception,has not yet been established.Second,although individual studies have explored factors affecting postoperative masticatory function,a systematic consensus has not been veached,leading to a lack of precision and individualization in clinical interventions,which significantly prolongs the patients'rehabilitation period.This paper reviews the scope and limitations of existing assessment tools for masticatory function in patients after mandibular reconstruction and systematically analyzes the key factors affecting postoperative masticatory function,aiming to promote a shift in clinical practice from"structural reconstruction"to a"function-perception collaborative rehabilitation"approach,and to provide a theoretical framework for constructing evidence-based,personalized masticatory rehabilitation programs.

Mandibular reconstruction refers to the restoration of the continuity of the mandible through techniques such as autologous bone grafting,thereby restoring the patient's basic appearance,reconstructing the occlusal relationship,and restoring functions such as opening the mouth,chewing,and swallowing,in order to achieve a unity of oral and maxillofacial forms and functions.Due to the fact that mastication necessitates the coordinated efforts of the masticatory muscles,mandible,dental arch,and tongue,the recovery of masticatory function not only serves as a robust indicator for the success of surgery but also enhances the patients'quality of life,facilitating an early return to normal life.Currently,for the rehabilitation of oral function in patients after mandibular reconstruction surgery,standardized tools have been established in the fields of swallowing,occlusion,and speech assessment,and targeted training has been implemented,yielding significant therapeutic outcomes.However,research related to masticatory function faces two major challenges.First,existing assessment tools primarily focus on a single dimension,such as masticatory efficiency or subjective perception,and an integrated assessment system that encompasses multiple dimensions,including bite force distribution and oral sensory perception,has not yet been established.Second,although individual studies have explored factors affecting postoperative masticatory function,a systematic consensus has not been veached,leading to a lack of precision and individualization in clinical interventions,which significantly prolongs the patients'rehabilitation period.This paper reviews the scope and limitations of existing assessment tools for masticatory function in patients after mandibular reconstruction and systematically analyzes the key factors affecting postoperative masticatory function,aiming to promote a shift in clinical practice from"structural reconstruction"to a"function-perception collaborative rehabilitation"approach,and to provide a theoretical framework for constructing evidence-based,personalized masticatory rehabilitation programs.

Heat shock factor 1(HSF1)is a core transcription factor in cellular stress response and protein homeostasis maintenance,and is widely involved in biological processes such as cell growth,differentiation,and metabolism.This study aims to design antigenic peptides of the sheep HSF1 protein and prepare polyclonal antibodies through bioinformatics analysis and immunologi-cal techniques,and verify their application effects in sheep lung and testis tissues.Firstly,the se-quence,structure,and evolution of the sheep HSF1 gene were analyzed using bioinformatics meth-ods,and key antigenic epitopes were predicted.Then,suitable peptide fragments were selected for synthesis,emulsified with Freund's complete adjuvant or incomplete adjuvant,and used to immu-nize New Zealand rabbits.The specificity and effectiveness of the antibodies were verified by indi-rect ELISA,Western blot,and immunohistochemistry(IHC)experiments.The results showed that the HSF1 protein is 564 amino acids(aa)in length,with a molecular weight of 60.76 kDa,a theo-retical isoelectric point(pI)of 5.32,and is hydrophilic and unstable.Phylogenetic tree analysis revealed that HSF1 is highly conserved among most members of the Bovidae family,as well as in humans,mice,rats,and other species,but with local site differences.Sheep HSF1 is most closely related to goat HSF1,followed by Canadian bighorn sheep and goral.The phosphorylation sites of sheep HSF1 are predominantly concentrated in the middle and C-terminal regions,which is largely consistent with the predicted results for human HSF1,though some local differences exist.The prepared polyclonal antibodies exhibited a titer of over 1:8000 in recognizing the sheep HSF1 pro-tein,and Western blot experiments confirmed clear bands with consistent molecular weight,indica-ting high specificity of the antibodies.Furthermore,the expression and specific distribution of HSF1 were detected in sheep lung and testis tissues.This study successfully prepared polyclonal antibodies based on the sheep HSF1 antigen peptide and,for the first time,detected the immuno-histochemical distribution of HSF1 in the testis and lung tissues of Argali hybrid sheep.This pro-vides an important tool for further exploring the physiological role of HSF1 in Argali hybrid sheep and its potential applications in stress response,disease prevention,and treatment.

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.

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.

Klebsiella pneumoniae(K.pneumoniae)is important zoonotic pathogen causing multiple local and systemic infections.At present,the drug resistance of K.pneumoniae is serious,and mul-tiple drug-resistant strains continue to emerge.Even the incidence of drug-resistant K.pneumoniae infection is increasing year by year.In this study,K.pneumoniae clinical isolate 71Y was used as the starting strain,and a phage with strong lytic activity was successfully obtained from sewage samples.The phage was named vB_KpnP_71Y(abbreviated as P71Y),the general biological char-acteristics and genome of P71Y were further studied and analyzed.P71Y can form clear plaque with a diameter of 2-5 mm and a translucent halo ring on the host bacterium 71Y lawn.Electron micros-copy observation shows that P71Y is a member of the order Autographiviridae and family Caudovi-rales.The incubation period for P71Y infected with K.pneumoniae is about 3 minutes,and one in-fection cycle lasts for about 50 minutes.Each infection of a bacterium can produce approximately 58 progeny phage virus particles.Cleavage spectra showed that the phage could lysate K20 and K57 serotypes of K.pneumoniae.The phage had good stability at 4-50 ℃ and pH values of 3-12.Genom-ic analysis revealed that P71Y contained a double-stranded DNA with a total length of 39 700 bp and a G+C content of 53％.There are a total of 53 coding genes,P71Y does not carry virulence factors and drug resistance genes,which has shown genetic safety.This study isolated a novel lytic phage that can cleave multiple serotypes of K.pneumoniae,which provided experimental materials for the study of the interaction between bacteriophages,different serotypes of K.pneumoniae,and the application of phage for the prevention and controlling of infections caused by multi-drug-re-sistant K.pneumoniae.

Objective:To evaluate the relationship between microRNA-27a (miR-27a) and silent information regulator 1 (SIRT1) during myocardial ischemia-reperfusion (I/R) in rats.Methods:Fifty clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 220-280 g, were divided into 5 groups ( n=10 each) by the random number table method: sham operation group (Sham group), myocardial I/R group (I/R group), AAV9-miR-27a overexpression + myocardial I/R group (AAV+ I/R group), miR-27a antagomir + myocardial I/R group (AG+ I/R group) and AAV9-miR-27a negative control+ myocardial I/R group (NC+ I/R group). The myocardial I/R injury model was prepared by ligating the anterior descending branch of the left coronary artery for 30 min followed by 120 min reperfusion. At day 14 before ischemia, AAV9-miRNA-27a adeno-associated virus 2×10 11 v. g was injected via the tail vein in AAV+ I/R group, and AAV9-miR-27a NC 2×10 11 v. g was injected via the tail vein in NC+ I/R group. miR-27a antagomir 10 mg/kg was injected via the tail vein once a day at 3 days before ischemia in AG+ I/R group. At the end of 120 min of reperfusion, serum cardiac troponin T(cTnT), creatine kinase isoenzymes (CK-MB) and lactic dehydrogenase (LDH) concentrations and contents of glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardial tissues were determined by enzyme-linked immunosorbent assay, the percentage of myocardial infarct volume by TTC staining, the expression of miR-27a in myocardial tissues by quantitative real-time polymerase chain reaction, and the expression of SIRT1 in myocardial tissues by Western blot. Results:Compared with Sham group, the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly increased, the contents of GSH and SOD in myocardial tissues were decreased, MDA contents were increased, miR-27a expression was up-regulated, and SIRT1 expression was down-regulated in I/R group ( P<0.05). Compared with I/R group, the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly increased, the contents of GSH and SOD in myocardial tissues were decreased, MDA contents were increased, miR-27a expression was up-regulated, and SIRT1 expression was down-regulated in AAV+ I/R, and the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly decreased, the contents of GSH and SOD in myocardial tissues were increased, MDA contents were decreased, miR-27a expression was down-regulated, and SIRT1 expression was up-regulated in AG+ I/R group ( P<0.05), and no significant change was found in the parameters mentioned above in NC+ I/R group ( P>0.05). Compared with AAV+ I/R group, the percentage of myocardial infarct volume and serum concentrations of cTnT, CK-MB and LDH were significantly decreased, the contents of GSH and SOD in myocardial tissues were increased, MDA contents were decreased, miR-27a expression was down-regulated, and SIRT1 expression was up-regulated in AG+ I/R group ( P<0.05). Conclusions:miR-27a is involved in the pathophysiological mechanism underlying myocardial I/R injury probably through inhibition of SIRT1 expression in rats.