Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

Objective:To evaluate the efficacy and safety of obinutuzumab combined with glucocorticoid-based therapy in patients with relapsed immune thrombotic thrombocytopenic purpura (iTTP).Methods:This study analyzed the efficacy and adverse reactions of four patients with relapsed iTTP who were treated with a combination of obinutuzumab and glucocorticoids to assess the effectiveness and safety of the treatment.Results:All four patients had a history of multiple relapses and had previously undergone treatment with rituximab and bortezomib. Three patients exhibited additional autoantibodies. Following the combined therapy, all patients achieved clinical remission, with ADAMTS13 activity returning to normal levels and inhibitors testing negative. During a median follow-up period of 11 months (range: 3–17 months), all patients maintained sustained remission. No severe adverse events were reported during treatment or follow-up.Conclusion:The combination of obinutuzumab and glucocorticoid-based therapy is effective and safe for treating relapsed iTTP.

Objective:To evaluate the efficacy and safety of obinutuzumab combined with glucocorticoid-based therapy in patients with relapsed immune thrombotic thrombocytopenic purpura (iTTP).Methods:This study analyzed the efficacy and adverse reactions of four patients with relapsed iTTP who were treated with a combination of obinutuzumab and glucocorticoids to assess the effectiveness and safety of the treatment.Results:All four patients had a history of multiple relapses and had previously undergone treatment with rituximab and bortezomib. Three patients exhibited additional autoantibodies. Following the combined therapy, all patients achieved clinical remission, with ADAMTS13 activity returning to normal levels and inhibitors testing negative. During a median follow-up period of 11 months (range: 3–17 months), all patients maintained sustained remission. No severe adverse events were reported during treatment or follow-up.Conclusion:The combination of obinutuzumab and glucocorticoid-based therapy is effective and safe for treating relapsed iTTP.

Objective:To evaluate the short-term efficacy of minimally invasive treatment of Sanders Ⅱ and Ⅲ calcaneal fractures in diabetes patients using subtalar arthroscopy assisted by preoperative musculoskeletal ultrasound to localize the lateral calcaneal branch of the sural nerve and a medial calcanetalar distractor.Methods:The clinical data of the 52 patients with diabetes mellitus were retrospectively analyzed who had been treated for Sanders Ⅱ and Ⅲ calcaneal fractures from March 2016 to August 2020 at Department of Traumatic Orthopedics, The Third Affiliated Hospital of Soochow University. There were 34 males and 18 females with an age of (61.7±14.5) years. According to the Sanders' classification, there were 23 cases of type Ⅱ and 29 cases of type Ⅲ. Preoperative musculoskeletal ultrasonography was routinely performed to locate the lateral calcaneal branch of the sural nerve in all patients. The surgical procedures were subtalar arthroscopy combined with percutaneous prying reduction and screw fixation assisted by a calcanetalar joint distractor. Incision healing, local skin paraesthesia and other conditions were observed regularly in all patients. The short-term efficacy was assessed by comparing calcaneal lengths, calcaneal widths, calcaneal heights, B?hler angles and Gissane angles at pre-surgery, 3 days, 12 months and the last follow-up after surgery, as well as by comparing visual analogue scale (VAS) pain scores, American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and Maryland scores at pre-surgery, 12 months and the last follow-up after surgery.Results:All the 52 patients were followed up for (23.7±3.2) months after successful surgery. No incision-related complications were reported. The calcaneal radiographic parameters (calcaneal lengths, calcaneal widths, calcaneal heights, B?hler angles and Gissane angles) at 3 days, 12 months and the last follow-up after surgery were significantly improved compared with the values before surgery ( P<0.05), but there were no significant differences regarding the calcaneal radiographic parameters between 3 days, 12 months and the last follow-up after surgery ( P>0.05). The VAS pain scores, AOFAS ankle-hindfoot scores and Maryland scores at 12 months and the last follow-up after surgery were significantly improved compared with those before surgery ( P<0.05). Conclusion:In the minimally invasive treatment of Sanders Ⅱ and Ⅲ calcaneal fractures in diabetes patients, preoperative musculoskeletal ultrasonography to locate the lateral calcaneal branch of the sural nerve, followed by subtalar arthroscopy combined with percutaneous prying reduction and screw fixation assisted by a calcanetalar joint distractor can lead to good short-term efficacy.

Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

Objective:To evaluate the short-term efficacy of minimally invasive treatment of Sanders Ⅱ and Ⅲ calcaneal fractures in diabetes patients using subtalar arthroscopy assisted by preoperative musculoskeletal ultrasound to localize the lateral calcaneal branch of the sural nerve and a medial calcanetalar distractor.Methods:The clinical data of the 52 patients with diabetes mellitus were retrospectively analyzed who had been treated for Sanders Ⅱ and Ⅲ calcaneal fractures from March 2016 to August 2020 at Department of Traumatic Orthopedics, The Third Affiliated Hospital of Soochow University. There were 34 males and 18 females with an age of (61.7±14.5) years. According to the Sanders' classification, there were 23 cases of type Ⅱ and 29 cases of type Ⅲ. Preoperative musculoskeletal ultrasonography was routinely performed to locate the lateral calcaneal branch of the sural nerve in all patients. The surgical procedures were subtalar arthroscopy combined with percutaneous prying reduction and screw fixation assisted by a calcanetalar joint distractor. Incision healing, local skin paraesthesia and other conditions were observed regularly in all patients. The short-term efficacy was assessed by comparing calcaneal lengths, calcaneal widths, calcaneal heights, B?hler angles and Gissane angles at pre-surgery, 3 days, 12 months and the last follow-up after surgery, as well as by comparing visual analogue scale (VAS) pain scores, American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores and Maryland scores at pre-surgery, 12 months and the last follow-up after surgery.Results:All the 52 patients were followed up for (23.7±3.2) months after successful surgery. No incision-related complications were reported. The calcaneal radiographic parameters (calcaneal lengths, calcaneal widths, calcaneal heights, B?hler angles and Gissane angles) at 3 days, 12 months and the last follow-up after surgery were significantly improved compared with the values before surgery ( P<0.05), but there were no significant differences regarding the calcaneal radiographic parameters between 3 days, 12 months and the last follow-up after surgery ( P>0.05). The VAS pain scores, AOFAS ankle-hindfoot scores and Maryland scores at 12 months and the last follow-up after surgery were significantly improved compared with those before surgery ( P<0.05). Conclusion:In the minimally invasive treatment of Sanders Ⅱ and Ⅲ calcaneal fractures in diabetes patients, preoperative musculoskeletal ultrasonography to locate the lateral calcaneal branch of the sural nerve, followed by subtalar arthroscopy combined with percutaneous prying reduction and screw fixation assisted by a calcanetalar joint distractor can lead to good short-term efficacy.

Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

Background and purpose:Hepatocellular carcinoma(HCC)is a major disease seriously threatening human health.Poly(ADP-ribose)polymerase-1(PARP1)is an enzyme that catalyzes poly ADP-ribosylation.Given the role of PARP1 in DNA damage repair,it is generally considered as an oncogene.However,the expression of PARP1 and its mechanism in HCC are not yet clear.This study aimed to investigate the role of PARP1 in the occurrence and development of HCC and its potential mechanisms.Methods:First,we analyzed the expression pattern of PARP1 in The Cancer Genome Atlas(TCGA)and Clinical Proteomic Tumor Analysis Consortium(CPTAC)HCC database,and identified the expression trend of PARP1 in our HCC cohort using real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Then,the enzyme activity of PARP1 was inhibited by PJ34,an inhibitor of PARP1 and the expression of PARP1 in HCC cell lines was downregulated with small RNA interference technology.Based on these models,the following experiments were conducted:First,the effect of PARP1 on cell viability was assessed by cell counting kit-8(CCK-8)assay and flow cytometry;Second,the expression levels of stemness-related genes in HCC cells were identified using RTFQ-PCR;Third,the effect of inhibition of PARP1 on migration and invasion of HCC cells was detected by migration and invasion assay(transwell assay).Finally,bioinformatic analysis was performed to identify new target genes and the pathways regulated by PARP1 in HCC progression.Rescue experiments were performed to determine whether PARP1 target genes were involved in the malignant phenotypes of HCC cells.Results:The expression of PARP1 was significantly up-regulated in HCC tissues in both TCGA and CPTAC database.RTFQ-PCR and Western blot assays showed that PARP1 was obviously up-regulated in HCC tissues compared to paracancerous tissues.Survival analysis showed that PARP1 expression was significantly negatively correlated with the prognosis of patients.The results of CCK-8,flow cytometry,RTFQ-PCR and transwell assay indicated that inhibition of PARP1 attenuated proliferation and activity of HCC cells,as well as weakened their stemness,migration and invasion.Bioinformatics analysis suggested that PARP1-regulated genes were enriched in the nuclear factor-κB(NF-κB)and necroptosis pathways,with POU class homeobox 2(POU2F2)potentially being a target gene of PARP1.Correlation analysis,along with RTFQ-PCR and Western blot detection,confirmed that the expression of POU2F2 was regulated by PARP1,while not affected by PJ34,indicating the effect of nonenzymatic function of PARP1 on POU2F2.CCK-8,flow cytometry and RTFQ-PCR results showed that the reintroduction of POU2F2 enhanced proliferative capacity,increased activity,and promoted stemness of HCC cell lines with PARP1 knockdown.Conclusion:By positively regulating the expression of POU2F2,PARP1 promotes malignant phenotypes of HCC cells,providing new insights for clinical treatment and drug development for HCC.

Surgery-based multidisciplinary comprehensive treatment is the preferred treatment strategy for local advanced esophageal cancer. Neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy have been recommended by the Chinese Society of Clinical Oncology (CSCO) guideline. With the advent of immunotherapy, neoadjuvant immunotherapy combined with chemotherapy has received much attention, and the first phase Ⅲ study has also confirmed that neoadjuvant immunotherapy combined chemotherapy is a promising treatment option. This article will review the recent advances and hot spots of neoadjuvant immunotherapy combined with chemotherapy.

This paper presents two cases of renal allograft parapelvic cysts treated with ureteroscopy involving internal incision and drainage using a holmium laser. The procedure also involved cyst puncture and injection of methylthioninium chloride, with ultrasound monitoring to determine the incision location based on the 'flame sign.' The surgeries were uneventful, and follow-up ultrasounds conducted 2 to 3 months later revealed a reduction in cyst size. This technique introduces a novel approach for treating parapelvic cysts in renal allografts.