ObjectiveTo investigate the status of overlapping hepatitis B virus （HBV） infection in patients with chronic hepatitis C virus （HCV） infection and the serological characteristics of such patients. MethodsA total of 8 637 patients with HCV infection who were hospitalized from January 1， 2010 to December 31， 2020 and had complete data of HBV serological markers were enrolled， and the composition ratio of patients with overlapping HBV serological markers was analyzed among the patients with HCV infection. The patients were divided into groups based on age and year of birth， and serological characteristics were analyzed， and the distribution of HBV-related serological characteristics were analyzed across different HCV genotypes. ResultsThe patients with HCV/HBV overlapping infection accounted for 5.85%， and the patients with previous HBV infection accounted for 48.10%； the patients with protective immunity against HBV accounted for 14.67%， while the patients with a lack of protective immunity against HBV accounted for 31.39%. The patients were divided into groups based on age： in the 0 — 17 years group， the patients with protective immunity against HBV accounted for 61.41% （304 patients）； the 18 — 44 years group was mainly composed of patients with previous HBV infection （698 patients， 37.31%）， the 45 — 59 years group was predominantly composed of patients with previous HBV infection （1 945 patients， 50.38%）， and the ≥60 years group was also predominantly composed of patients with previous HBV infection （1 486 patients， 61.66%）. The patients were divided into groups based on the year of birth： in the pre-1992 group， the patients with previous HBV infection accounted for 51.63% （4 112 patients）； in the 1992 — 2005 group， the patients with protective immunity against HBV accounted for 54.72% （168 patients）； in the post-2005 group， the patients with protective immunity against HBV accounted for 64.38% （235 patients）. In this study， 6 301 patients underwent HCV genotype testing： the patients with genotype 1b accounted for the highest proportion of 51.71% （3 258 patients）， followed by those with genotype 2a （1 769 patients， 28.07%）， genotype 3b （63 patients， 1.00%）， genotype 3a （10 patients， 0.16%）， genotype 4 （21 patients， 0.33%）， and genotype 6a （5 patients， 0.08%）. ConclusionWith the implementation of hepatitis B planned vaccination program in China， there has been a significant reduction in the proportion of patients with previous HBV infection among the patients with HCV/HBV overlapping infection， but there is still a relatively high proportion of patients with a lack of protective immunity against HBV.

Objective Exploring the clinical efficacy of using autologous rib cartilage grafting to reconstruct finger hemiarticular defects.Methods From August 2022 to February 2024,for 6 patients with hemiarticular surface defects in the metacarpophalangeal joints and interphalangeal joints of 8 fingers,costal cartilage was used for joint remodeling and transplantation to reconstruct the hemiarticular surface defects of the fingers.All 8 joint transplants in 6 patients were two-stage surgeries.In the first stage,antibiotic bone cement was used to fill the space-occupying lesions,and in the second stage,costal cartilage joint remodeling was performed to reconstruct the finger joint defects.Postoperative follow-up and assessment of fracture healing according to Paley fracture healing scoring criteria.Outpatient and WeChat follow-up,upper limb function is evaluated according to the upper limb functional assessment standards of the Chinese Medical Association Hand Surgery Society.Record VAS pain score.Results In this group,there were a total of 6 patients with 8 cases of hemiarticular defects.Among them,2 patients had two joint surgical sites,while the remaining 4 patients had a single joint surgical site.There were 2 cases of metacarpophalangeal joint head defects,2 cases of proximal articular surface defects,3 cases of proximal articular head defects,and 1 case of thumb proximal articular head defect.After surgery,8 out of 6 patients'hand wounds healed successfully.All patients were followed up for 6-12 months postoperatively,with an average of 9 months.The VAS pain score(affected finger)for the last follow-up was 0-2 points,with an average of 0.6 points.According to Paley's scoring criteria,all 6 patients had excellent fracture healing.According to the evaluation criteria for upper limb functional assessment of the Chinese Medical Association Hand Surgery Society,3 cases were rated as excellent,3 cases were rated as good,and 2 cases were rated as fair.Conclusion For patients with half joint defects on one side of the finger,rib rib cartilage was used for joint reconstruction,which significantly improved the joint shape and function at the defect site,and reduced joint pain scores.

Objective:To investigate the effects and molecular mechanisms of Wilms tumor 1-associated proteins(WTAP)on the cell biological properties of esophageal squamous cell carcinoma(ESCC)cells.Methods:31 pairs of ESCC tissues and their paired paracancerous tissues that were surgically resected at the Second Clinical Medical College of Chuanbei Medical College between September 2019 and April 2021 were collected.The esophageal cancer cells KYSE30,KYSE410,KYSE150,KYSE510,TE-1,and normal human esophageal epithelial cells HET-1A were routinely cultured.Transfection reagents were used to transfect si-NC,si-WTAP#1 and si-WTAP#2 nucleic acids into KYSE150 and KYSE510 cells.The cells were divided into si-NC,si-WTAP#1 and si-WTAP#2 groups.The expressions of WTAP and MAP3K9 mRNA were detected in the cells of each group by qPCR assay.CCK-8 assay,clone formation assay,and scratch healing assay,Transwell assay were employed to detect the effects of knockdown of WTAP expression on ESCC cell proliferation,migration,invasion and apoptosis.WB assay was used to detect the expressions of WTAP,MAP3K9,EMT and MAPK pathway-related proteins in ESCC cells of each group knocked down of WTAP;immunohistochemistry to detect the expression of WTAP proteins in ESCC tissues,immunoprecipitation of methylated RNA(MeRIP)-qPCR assay to detect the level of MAP3K9 m6A in ESCC cells,actinomycin D assay to detect the stability of mRNA of MAP3K9,and database data to analyze the expression,target genes,functional enrichment,and interacting RNA of WTAP.Results:WTAP was highly expressed in ESCC tissues and cells(P<0.05 or P<0.01 or P<0.001)and correlated with the degree of differentiation(P<0.01);the expression of WTAP mRNA and its protein were successfully knocked down in KYSE150 and KYSE510 cells(P<0.01 or P<0.001);the knockdown of WTAP significantly inhibited the proliferation,migration and invasion of KYSE150 and KYSE510 cells(P<0.05 or P<0.01 or P<0.001),and promoted the apoptosis of KYSE150 and KYSE510 cells(P<0.05 or P<0.01).Knockdown of WTAP resulted in a significant decrease in the m6A level of MAP3K9(P<0.05),and its mRNA expression level and mRNA stability were both significantly reduced(P<0.05).Database data analysis showed that WTAP target genes clustered in the MAPK signaling pathway;the expression levels of MAP3K9,p-ERK,N-cadherin,and MMP9 were significantly reduced(P<0.05 or P<0.01),and the expression level of E-cadherin was significantly elevated(P<0.05 or P<0.01)in the KYSE150 and KYSE510 cells after knockdown of WTAP.Conclusions:WTAP is highly expressed in ESCC tissues and cells and correlates with their differentiation.It promotes the stability of MAP3K9 mRNA through m6A modification,activates the MAPK pathway and thus promotes the malignant biological behaviors of ESCC cells.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To investigate the therapeutic effect of Sheng Mai San mixed Jiawei Sheng Xian Tang on patients with heart failure with reduced ejection fraction(HFrEF)of Qi deficiency blood stasis type,and its impact on the immune inflammatory response of patients.Methods Ninety patients with HFrEF of Qi deficiency blood stasis type were selected and divided into two groups according to the treatment plan.Patients of the conventional group(42 cases)took sacubitril/valsartan sodium tablets orally.Patients of the combined group(48 cases)were treated with Sheng Mai San combined with Jiawei Sheng Xian Tang on the basis of the conventional group,one dose per day,and divided it in two servings used in the morning and evening.The symptoms of the patients were evaluated by using traditional Chinese medicine(TCM)syndrome score before and after the treatment respectively.Echocardiography technology was used to measure the left ventricular end-diastolic diameter(LVEDD)and left ventricular ejection fraction(LVEF).Enzyme-linked immunosorbent assay was used to detect pentaggrin 3(PTX3),tumor necrosis factor-α(TNF-α),galectin-3(Gal-3),interleukin(IL)-8,IL-6,IL-33 and angiotensin Ⅱ(Ang Ⅱ).N-terminal pro-brain natriuretic peptide(NT-proBNP)was detected by immunofluorescence analysis.The therapeutic effect was evaluated based on the symptoms and the New York Heart Association(NYHA)cardiac function classification in the United States.Results After treatment,the levels of TCM syndrome scores,LVEDD,TNF-α,PTX3,IL-8,IL-6,IL-33,NT-proBNP,Gal-3 and AngⅡ decreased in both groups,and those in the combined group were lower than those in the conventional group(P＜0.05).The LVEF increased,and which were higher in the combined group than those of the conventional group(P＜0.05).After the treatment,the total effective rate of the combined group was higher than that of the conventional group(P＜0.05).Conclusion The Sheng Mai San mixed Jiawei Sheng Xian Tang as adjuvant therapy can effectively reduce the levels of immune inflammatory cytokines in HFrEF patients of Qi deficiency blood stasis type,improve their clinical symptoms and enhance therapeutic effect.

Objective To investigate the therapeutic effect of Sheng Mai San mixed Jiawei Sheng Xian Tang on patients with heart failure with reduced ejection fraction(HFrEF)of Qi deficiency blood stasis type,and its impact on the immune inflammatory response of patients.Methods Ninety patients with HFrEF of Qi deficiency blood stasis type were selected and divided into two groups according to the treatment plan.Patients of the conventional group(42 cases)took sacubitril/valsartan sodium tablets orally.Patients of the combined group(48 cases)were treated with Sheng Mai San combined with Jiawei Sheng Xian Tang on the basis of the conventional group,one dose per day,and divided it in two servings used in the morning and evening.The symptoms of the patients were evaluated by using traditional Chinese medicine(TCM)syndrome score before and after the treatment respectively.Echocardiography technology was used to measure the left ventricular end-diastolic diameter(LVEDD)and left ventricular ejection fraction(LVEF).Enzyme-linked immunosorbent assay was used to detect pentaggrin 3(PTX3),tumor necrosis factor-α(TNF-α),galectin-3(Gal-3),interleukin(IL)-8,IL-6,IL-33 and angiotensin Ⅱ(Ang Ⅱ).N-terminal pro-brain natriuretic peptide(NT-proBNP)was detected by immunofluorescence analysis.The therapeutic effect was evaluated based on the symptoms and the New York Heart Association(NYHA)cardiac function classification in the United States.Results After treatment,the levels of TCM syndrome scores,LVEDD,TNF-α,PTX3,IL-8,IL-6,IL-33,NT-proBNP,Gal-3 and AngⅡ decreased in both groups,and those in the combined group were lower than those in the conventional group(P＜0.05).The LVEF increased,and which were higher in the combined group than those of the conventional group(P＜0.05).After the treatment,the total effective rate of the combined group was higher than that of the conventional group(P＜0.05).Conclusion The Sheng Mai San mixed Jiawei Sheng Xian Tang as adjuvant therapy can effectively reduce the levels of immune inflammatory cytokines in HFrEF patients of Qi deficiency blood stasis type,improve their clinical symptoms and enhance therapeutic effect.

Objective:To construct a prognostic risk model based on lactate metabolism-related genes screened using bioinformatics methods in renal cell carcinoma patients，and investigate the clinical prognosis and immune characteristics of renal cell carcinoma.Methods:Gene expression data and clinical information of patients with renal cell carcinoma were downloaded from the Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma（TCGA-KIRC）dataset. Lactate metabolism-related gene sets were obtained from the Gene Set Enrichment Analysis（GSEA）database. The R package DEseq2 was employed to identify differentially expressed genes associated with lactate metabolism within the TCGA-KIRC dataset. GO and KEGG enrichment analyses were performed using the clusterProfiler package. Prognosis-related genes were screened via univariate Cox regression analysis and the intersection with lactate metabolism-related differentially expressed genes was obtained. A risk model was constructed using LASSO regression followed by multivariate Cox regression analysis to calculate risk scores. This risk model was subsequently validated using the GSE29609 dataset. Patients were stratified into high-risk and low-risk groups based on the median risk score. The expression profiles of key immune molecule genes and immune checkpoint genes were compared between the two groups. Survival analysis curves for immune checkpoint genes were generated using the survival and survminer R packages. Differences in tumor mutation burden（TMB）between the high-risk and low-risk groups were assessed，and corresponding TMB survival analysis curves were plotted. Finally，the tumor immune dysfunction and exclusion（TIDE）algorithm was used to evaluate disparities in immunotherapy response potential between the two risk groups.Results:An optimal prognostic risk model incorporating seven lactate metabolism- and prognosis-related genes（ LDHD，PER2，ACADM，FLI1，LIPA，TCIRG1，SLC25A4）was constructed and successfully validated in the GSE29609 dataset. Univariate Cox regression analysis revealed that a high-risk score was significantly associated with poor prognosis（ HR=2.915，95% CI：2.451-3.470， P<0.001）. Multivariate Cox regression analysis confirmed that this risk model could serve as an independent prognostic factor for patients with renal cell carcinoma（ HR=2.231，95% CI：1.829-2.722， P<0.001）. Patients in the high-risk group exhibited significantly worse outcomes compared to the low-risk group，regardless of whether they had early-stage or advanced-stage renal cell carcinoma（both P<0.001）. Analyses related to the immune microenvironment indicated an upregulated immunosuppressive phenotype in the high-risk group. Furthermore，the TMB was significantly higher in the high-risk group than in the low-risk group（ P=0.032），and patients within the high-risk group exhibiting higher TMB levels demonstrated even poorer survival（ P<0.001）. Finally，the TIDE score was significantly elevated in the high-risk group in comparison to the low-risk group（ P<0.001）. Conclusions:The risk model based on lactate metabolism-related genes constructed in this study can guide the prognosis of renal cell carcinoma. Patients in the high-risk group are more prone to immune escape and formation of an inhibitory immune microenvironment，leading to worse prognoses. This risk model may serve as a biomarker for predicting immunotherapy response.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Over the past decade, pathology technology in China has undergone rapid development. Through continuous efforts to strengthen normative foundations and quality control, the three-tiered quality control network (national, provincial, and municipal) has been consolidated. These efforts have effectively driven the homogenization of pathology technical quality nationwide. Concurrently, the standardization of laboratory quality management systems and the advancement of automated pathological equipment have laid a solid foundation for the evolution of pathological diagnosis. Breakthroughs in cutting-edge technologies, including digital pathology, artificial intelligence, and molecular pathology, are further catalyzing a paradigm shift from traditional morphological analysis toward next-generation diagnostic pathology. Marking the 70th anniversary of this journal, the field's evolution over the past decade and chart its future course were reviwed systematically, aiming to provide an insightful roadmap for the ongoing progress of the discipline.