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.

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.

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.

Objective:To compare the self-evaluated learning behavior and achievement of eight-year-program clinical medical students on online and offline problem-based learning (PBL), and to provide references and suggestions for successful implementation of online PBL teaching.Methods:During the three semesters of September 2020 to January 2022, a survey was performed on 100 clinical medical students of 2018 eight-year program on online or offline PBL teaching in Xiangya School of Medicine, Central South University. At the end of PBL courses, the students received questionnaires to self-assess their learning behavior and achievement in online or offline PBL teaching. The data were analyzed using the paired rank sum test with the use of SPSS 26.0.Results:Before class, there were no significant differences in learning behaviors including preparation time, communication with classmates, and materials collecting and sorting between students on online and offline PBL teaching ( P>0.05). In class, no significant differences were found in students' initiative of speaking and degree of satisfaction with classmates' speaking between online and offline teaching ( P>0.05), but the students on offline teaching showed significantly better concentration of attention ( Z=-4.24, P<0.001), listening to classmates' speeches ( Z=-3.42, P=0.001), and classmates' interaction ( Z=-3.11, P=0.002) compared with those on online teaching. No significant differences were observed between online and offline PBL teaching in students' self-evaluated learning achievements including improvements in autonomous learning ability, problem-solving ability, and literature inquiry skills ( P>0.05). Conclusion:Students on online PBL teaching have generally as good pre-class preparation and in-class learning performance as those on offline PBL teaching, indicating that the online PBL mode can be well implemented, and it can also ensure almost the same learning achievement as offline teaching.

Objective:To observe the lipid-lowering effect of atorvastatin on patients with acute cerebral infarction with different ATP-binding cassette subfamily B member 1(ABCB1) genotypes, and thus to provide clinical research evidence for individual application of atorvastatin in patients with acute cerebral infarction.Methods:From March 2021 to December 2021, 131 patients with acute cerebral infarction admitted to the Department of Neurology of Xuchang Central Hospital were included. The ABCB1 G2677T gene polymorphism rs2032582 of patients was detected by fluorescence staining in situ hybridization.Based on the detection results, patients were divided into GG group, GT group and TT group.All patients were given atorvastatin (20 mg/d) for lipid-lowering treatment.The levels of low density lipoprotein cholesterol(HDL-C), high density lipoprotein cholesterol(HDL-C), total cholesterol(TC)and triglyceride(TG) in serum of patients in the three groups before and 2 months after treatment were recorded and analyzed.The adverse drug reactions in the three groups were recorded. When the serum LDL-C level was less than 1.8 mmol/L, it was considered that the lipid-lowering treatment was effective.The binary Logistic regression analysis was used to explore the influencing factors of atorvastatin lipid lowering therapy.The software of SPSS 25.0 was used for statistical analysis.Results:There were 50 (38.17%), 49 (37.40%) and 32 (24.43%) patients in GG group, GT group and TT group, respectively. The serum TC levels of patients in GG group, GT group and TT group after treatment were (3.47±0.70) mmol/L, (3.59±1.09) mmol/L and (3.48±1.02) mmol/L, respectively, which were lower than those before treatment ((4.27± 0.99) mmol/L, (4.02±0.98) mmol/L and (4.03±1.31) mmol/L), all of which were statistically significant ( t=7.652, 3.092, 5.593, all P<0.01). The serum LDL-C levels in GG group, GT group and TT group after treatment were (1.89±0.53) mmol/L, (2.07±0.92) mmol/L and (1.96±0.79) mmol/L, respectively, which were lower than those before treatment ((2.87±0.92) mmol/L, (2.56±0.89) mmol/L and (2.55±1.11) mmol/L) ( t=9.896, 4.055, 5.980, all P<0.001). The differences of serum LDL-C level before and after treatment in GG group, GT group and TT group were (-0.97±0.69) mmol/L, (-0.50±0.86) mmol/L and (-0.59±0.56) mmol/L, respectively. The difference of serum LDL-C level before and after treatment in the three groups was statistically significant ( F=5.614, P=0.005). The difference of TC, TG and HDL-C before and after treatment was not statistically significant( F=2.783, 0.490, 1.677, all P>0.05). The binary Logistic regression analysis showed that ABCB1 G2677T gene type and staying up late were independent influencing factors for atorvastatin lipid-lowering therapy. The probability of effective lipid-lowering in GT patients with ABCB1 G2677T gene was 27.9% of that in GG patients ( OR=0.279, 95% CI: 0.110-0.709, P=0.007), and the probability of TT type patients was 33.8% of GG type patients ( OR=0.338, 95% CI: 0.121-0.943, P=0.038). The probability of effective lipid-lowering in patients who had the habit of staying up late was 26.4% of the patients who did not stay up late ( OR=0.264, 95% CI: 0.118-0.591, P=0.001). There was no significant difference in the total incidence of adverse drug reactions among the three groups( χ2=0.868, P=0.648). Conclusion:The lipid-lowering effect in patients with GG type of ABCB1 G2677T is better than that of GT type and TT type when atorvastatin is used to treat patients with acute cerebral infarction.

Objective:To investigate the clinical application of Grunenwald incision in cervicothoracic junction surgery.Methods:The clinical data of 25 patients with cervicothoracic junction tumor and 1 patient with cervicothoracic junction trauma in the single treatment group of Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from December 2011 to September 2021 were analyzed retrospectively, including 19 males and 7 females, aged 9-73 years old. Among the 26 patients, there were 9 cases of upper mediastinal tumor, 6 cases of superior sulcus tumor, 4 cases of thyroid tumor invading the upper mediastinal, 4 cases of chest wall tumor, 2 cases of esophageal cancer combined with supraclavicular lymph node metastasis, and 1 case of foreign body penetrating injury at the cervicothoracic junction. Grunenwald incision or additional posterolateral thoracic incision, median sternal incision, neck collar incision were used in all patients. The degree of tumor resection was evaluated. The operation time, intraoperative blood loss, length of hospital stay were observed, and the postoperative follow-up was analyzed.Results:There was no perioperative death in the whole group. 14 cases were treated with Grunenwald incision alone, 6 cases with additional posterolateral chest incision, 4 cases with additional neck collar incision, and 2 cases with additional median sternal incision. The tumors were completely resection in 22 cases, palliative tumor resection in 3 cases, and complete foreign body removal in 1 case. Postoperative pathology included 4 cases of schwannoma; 3 cases of lung adenocarcinoma, thyroid cancer and myofibroblastoma, respectively; 2 cases of supraclavicular lymph node metastasis of esophageal cancer and lung squamous carcinoma, respectively; 1 case of large cell neuroendocrine carcinoma, metastatic carcinoma of the first rib after lung squamous cell carcinoma, ganglioneuroma, nodular goiter, hemangioma, well differentiated liposarcoma, vascular endothelial tumor and cavernous angioma, respectively. The operation time was 120-430 min, with a mean of(226.92±88.40)min. The intraoperative blood loss was 100-1 000 ml, with a mean of(273.46±196.34)ml. The length of hospital stay was 6-26 days, with a mean of(12.73±4.46 )days. 26 patients were followed up for 6-130 months, with a mean of(57.88±43.64) months. During the follow-up period, 6 patients died.Conclusion:Grunenwald incision can provide good exposure of the structures near the cervicothoracic junction, preserve the integrity of sternoclavicular joint, reduce shoulder deformity, and has advantages for patients with cervicothoracic junction tumors, high rib resection, and cervicothoracic junction trauma.

Objective     To explore the causes of conversion to thoracotomy in patients with minimally invasive esophagectomy (MIE) in a surgical team, and to obtain a deeper understanding of the timing of conversion in MIE. Methods     The clinical data of patients who underwent MIE between September 9, 2011 and February 12, 2022 by a single surgical team in the Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. The main influencing factors and perioperative mortality of patients who converted to thoracotomy in this group were analyzed. Results     In the cohort of 791 consecutive patients with MIE, there were 520 males and 271 females, including 29 patients of multiple esophageal cancer, 156 patients of upper thoracic cancer, 524 patients of middle thoracic cancer, and 82 patients of lower thoracic cancer. And 46 patients were converted to thoracotomy for different causes. The main causes for thoracotomy were advanced stage tumor (26 patients), anesthesia-related factors (5 patients), extensive thoracic adhesions (6 patients), and accidental injury of important structures (8 patients). There was a statistical difference in the distribution of tumor locations between patients who converted to thoracotomy and the MIE patients (P<0.05). The proportion of multiple and upper thoracic cancer in patients who converted to thoracotomy was higher than that in the MIE patients, while the proportion of lower thoracic cancer was lower than that in the MIE patients. The perioperative mortality of the thoracotomy patients was not significantly different from that of the MIE patients (P=1.000). Conclusion     In MIE, advanced-stage tumor, anesthesia-related factors,extensive thoracic adhesions, and accidental injury of important structures are the main causes of conversion to thoracotomy. The rate varies at different tumor locations. Intraoperative conversion to thoracotomy does not affect the perioperative mortality of MIE.

Objective:To investigate the therapeutic efficiency of multiple forms of microdissected perforator flaps in the reconstruction of limb defect.Methods:The data of patients treated in the Department of Hand Surgery of Xuzhou Renci Hospital from June 2020 to June 2022 for repairing wound of hands, feet, limbs and popliteal fosses with microdissected perforator flap were retrospectively analyzed. CT angiography and color Doppler ultrasound were performed in all patients before surgery to locate perforator vessels, design the donor flap, and cut the flap retrograde according to the design line. After confirming good blood supple, the flap was harvested under the microscope, and fat particles were cut around the vascular pedicle by "insect eating" technique. After that, the flap was transferred to the recipient area, completed the vascular anastomosis, and placed the drainage tube. The donor site was closed directly. The blood circulation of the flap was observed closely after operation. Regular follow-up visits were conducted in outpatient clinics, door-to-door visits and WeChat to record sensory recovery and complications. Postoperative wound healing, flap shape, flap sensation, flap temperature and scar in donor area were evaluated using the efficacy satisfaction scale, which was divided into four grades: excellent (2 points), good (1 point), fair (0 point) and poor (-1 point). The total score of 5-10 was satisfactory, 0-4 was average, and -1--5 was unsatisfactory.Results:A total of 16 patients were included, including 8 males and 8 females. The age ranged from 26 to 65 years, with an average age of 45.9 years. There were 2 cases of upper limb soft tissue defect, 2 cases of hand degloving injury, 11 cases of hand skin soft tissue defect, and 1 case of popliteal soft tissue defect. The wound size ranged from 3.0 cm×4.5 cm to 13.0 cm×30.0 cm. Free medial sural artery perforator flap was used in 4 cases, interosseous dorsal artery perforator flap in 1 case, anterolateral femoral perforator flap in 6 cases, thoracic umbilical flap in 1 case, anterolateral femoral perforator flap combined with superficial circumflex iliac artery perforator flap in 1 case, and superficial circumflex iliac artery perforator flap in 3 cases. The size of the skin flap was 3.5 cm×5.0 cm - 9.5 cm×30.0 cm. After operation, 15 cases of flaps successfully survived, 1 case of venous crisis occurred 1 day after operation, and successfully survived after exploration and re-anastomosis of blood vessels. The wounds in the donor area healed in one stage without wound infection, delayed healing and other complications. All patients were follow-up for 7 to 18 months (mean 12.1 months), the skin flap survived well, no pigmentation, bloated appearance, and no patients requested secondary thinning treatment. The skin flap sensation recovered light touch in 1 case, protective sense in 9 cases and deep touch only in 6 cases. No significant thickening of skin flap was observed in the later period of follow-up, and skin flap wear was observed in 1 patient. There were only linear scars left in the donor area, and there were no obvious abnormalities in appearance and function. Efficacy satisfaction evaluation showed that all patients were satisfied with the therapeutic effect, scoring 6-9 points, with an average of 7.8 points.Conclusion:Microdissected perforator flap technique provides a one-stage surgical solution for aesthetic and functional areas with high requirements, and satisfactory clinical efficiencies can be obtained.

Objective:To investigate the therapeutic efficiency of multiple forms of microdissected perforator flaps in the reconstruction of limb defect.Methods:The data of patients treated in the Department of Hand Surgery of Xuzhou Renci Hospital from June 2020 to June 2022 for repairing wound of hands, feet, limbs and popliteal fosses with microdissected perforator flap were retrospectively analyzed. CT angiography and color Doppler ultrasound were performed in all patients before surgery to locate perforator vessels, design the donor flap, and cut the flap retrograde according to the design line. After confirming good blood supple, the flap was harvested under the microscope, and fat particles were cut around the vascular pedicle by "insect eating" technique. After that, the flap was transferred to the recipient area, completed the vascular anastomosis, and placed the drainage tube. The donor site was closed directly. The blood circulation of the flap was observed closely after operation. Regular follow-up visits were conducted in outpatient clinics, door-to-door visits and WeChat to record sensory recovery and complications. Postoperative wound healing, flap shape, flap sensation, flap temperature and scar in donor area were evaluated using the efficacy satisfaction scale, which was divided into four grades: excellent (2 points), good (1 point), fair (0 point) and poor (-1 point). The total score of 5-10 was satisfactory, 0-4 was average, and -1--5 was unsatisfactory.Results:A total of 16 patients were included, including 8 males and 8 females. The age ranged from 26 to 65 years, with an average age of 45.9 years. There were 2 cases of upper limb soft tissue defect, 2 cases of hand degloving injury, 11 cases of hand skin soft tissue defect, and 1 case of popliteal soft tissue defect. The wound size ranged from 3.0 cm×4.5 cm to 13.0 cm×30.0 cm. Free medial sural artery perforator flap was used in 4 cases, interosseous dorsal artery perforator flap in 1 case, anterolateral femoral perforator flap in 6 cases, thoracic umbilical flap in 1 case, anterolateral femoral perforator flap combined with superficial circumflex iliac artery perforator flap in 1 case, and superficial circumflex iliac artery perforator flap in 3 cases. The size of the skin flap was 3.5 cm×5.0 cm - 9.5 cm×30.0 cm. After operation, 15 cases of flaps successfully survived, 1 case of venous crisis occurred 1 day after operation, and successfully survived after exploration and re-anastomosis of blood vessels. The wounds in the donor area healed in one stage without wound infection, delayed healing and other complications. All patients were follow-up for 7 to 18 months (mean 12.1 months), the skin flap survived well, no pigmentation, bloated appearance, and no patients requested secondary thinning treatment. The skin flap sensation recovered light touch in 1 case, protective sense in 9 cases and deep touch only in 6 cases. No significant thickening of skin flap was observed in the later period of follow-up, and skin flap wear was observed in 1 patient. There were only linear scars left in the donor area, and there were no obvious abnormalities in appearance and function. Efficacy satisfaction evaluation showed that all patients were satisfied with the therapeutic effect, scoring 6-9 points, with an average of 7.8 points.Conclusion:Microdissected perforator flap technique provides a one-stage surgical solution for aesthetic and functional areas with high requirements, and satisfactory clinical efficiencies can be obtained.