Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City,China. Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed. Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52％. The male:female ratio was 2.8:1. 75.3％ of patients were aged between 16 and 60 years old,75.3％ of patients were farmers,and 11.6％ had both "three red" and "three pain" symptoms. The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak. Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity. The typical symptoms of "three red" and"three pain" in patients with HFRS were not obvious.

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 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.

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

Objective:To explore the clinical features and survival of newly diagnosed follicular lymphoma (FL) patients with diffuse large B-cell lymphoma (DLBCL) component.Methods:1845 newly diagnosed FL patients aged ≥ 18 years with grades 1-3a in 11 medical centers in China from 2000 to 2020 were included, and patients with DLBCL component were screened. The clinical data and survival data of the patients were retrospectively analyzed, and the prognostic factors were screened by univariate and multivariate analysis.Results:146 patients (7.9% ) with newly diagnosed FL had DLBCL component. The median age was 56 (25-83) years, 79 males (54.1% ) . The pathology of 127 patients showed the proportion of DLBCL component. Patients were divided into two groups according to whether the proportion of DLBCL component was ≥ 50% . The study found that patients with DLBCL component ≥ 50% had higher grade 3 ratio (94.3% vs 91.9% , P=0.010) , Ki-67 index ≥ 70% ratio (58.5% vs 32.9% , P=0.013) and PET-CT SUVmax ≥ 13 ratio (72.4% vs 46.3% , P=0.030) than patients with DLBCL component<50% . All patients received CHOP or CHOP like ± rituximab chemotherapy. The overall response rate (ORR) was 88.2% , and the complete response (CR) rate was 76.4% . In the groups with different proportions of DLBCL component, there was no significant difference in the remission rate after induction treatment and the incidence of disease progression within 2 years after initiation of treatment (POD24) ( P<0.05) . The overall estimated 5-year progression free survival (PFS) rate was 58.9% , and the 5-year overall survival (OS) rate was 90.4% . The 5-year OS rate of POD24 patients was lower than that of non POD24 patients (70.3% vs 98.5% , P<0.001) . Compared with non maintenance treatment of rituximab, maintenance treatment of rituximab could not benefit the 5-year PFS rate (57.7% vs 58.8% , P=0.543) , and the 5-year OS rate had a benefit trend, but the difference was not statistically significant (100% vs 87.8% , P=0.082) . Multivariate analysis showed that failure to reach CR after induction treatment was an independent risk factor for PFS ( P=0.006) , while LDH higher than normal was an independent risk factor for OS ( P=0.031) . Conclusion:FL patients with DLBCL component ≥50% have more invasive clinical and pathological features. CHOP/CHOP like ± rituximab regimen can improve the clinical efficacy of patients. Rituximab maintenance therapy can not benefit the PFS and OS of patients. Failure to reach CR after induction therapy was the independent unfavorable factor for PFS.

Background::The study aimed to clarify the characteristics of lymph node metastasis (LNM) and to compare the oncologic outcomes of minimally invasive esophagectomy (MIE) with open esophagectomy (OE) in terms of lymph node dissection (LND) in thoracic esophageal cancer patients.Methods::The data from esophageal cancer patients who underwent MIE or OE from January 2016 to January 2019 were retrospectively reviewed. The characteristics of LNM in thoracic esophageal cancer were discussed, and the differences in numbers of LND, LND rate, and LNM rate/degree of upper mediastinum between MIE and OE were compared.Results::For overall characteristics of LNM in 249 included patients, the highest rate of LNM was found in upper mediastinum, while LNM rate in middle and lower mediastinum, and abdomen increased with the tumor site moving down. The patients were divided into MIE ( n = 204) and OE groups ( n = 45). In terms of number of LND, there were significant differences in upper mediastinum between MIE and OE groups (8 [5, 11] vs. 5 [3, 8], P < 0.001). The comparative analysis of regional lymph node showed there was no significant difference except the subgroup of upper mediastinal 2L and 4L group (3 [1, 5] vs. 0 [0, 2], P < 0.001 and 0 [0, 2] vs. 0, P = 0.012, respectively). Meanwhile, there was no significant difference in terms of LND rate except 2L (89.7% [183/204] vs. 71.1% [32/45], P = 0.001) and 4L (41.2% [84/204] vs. 22.2% [10/45], P = 0.018) groups. For LNM rate of T3 stage, there was no significant difference between MIE and OE groups, and the comparative analysis of regional lymph node showed that there was no significant difference except 2L group (11.1% [5/45] vs. 38.1% [8/21], P = 0.025). The LNM degree of OE group was significantly higher than that of MIE group (27.2% [47/173] vs. 7.6% [32/419], P < 0.001), and the comparative analysis of regional LNM degree showed that there was no significant difference except 2L (34.7% [17/49] vs. 7.7% [13/169], P < 0.001) and 4L (23.8% [5/21] vs. 3.9% [2/51], P= 0.031) subgroups. Conclusion::MIE may have an advantage in LND of upper mediastinum 2L and 4L groups, while it was similar to OE in other stations of LND.

Cell migration is defined as the directional movement of cells toward a specific chemical concentration gradient, which plays a crucial role in embryo development, wound healing and tumor metastasis. However, current research methods showed low flux and are only suitable for single-factor assessment, and it was difficult to comprehensively consider the effects of other parameters such as different concentration gradients on cell migration behavior. In this paper, a four-channel microfluidic chip was designed. Its characteristics were as follows: it relied on laminar flow and diffusion mechanisms to establish and maintain a concentration gradient; it was suitable for observation of cell migration in different concentration gradient environment under a single microscope field; four cell isolation zones (20 μm width) were integrated into the microfluidic device to calibrate the initial cell position, which ensured the accuracy of the experimental results. In particular, we used COMSOL Multiphysics software to simulate the structure of the chip, which demonstrated the necessity of designing S-shaped microchannel and horizontal pressure balance channel to maintain concentration gradient. Finally, neutrophils were incubated with advanced glycation end products (AGEs, 0, 0.2, 0.5, 1.0 μmol·L ^-1), which were closely related to diabetes mellitus and its complications. The migration behavior of incubated neutrophils was studied in the 100 nmol·L ^-1 of chemokine (N-formylmethionyl-leucyl-phenyl-alanine) concentration gradient. The results prove the reliability and practicability of the microfluidic chip.
Cell Movement ; Chemotaxis ; Equipment Design ; Lab-On-A-Chip Devices ; Microfluidic Analytical Techniques ; Microfluidics ; Neutrophils ; Reproducibility of Results

Objective:To investigate the clinicopathological characteristics and prognostic factors of patients with esophageal cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 447 patients with esophageal cancer who were admitted to the Fourth Hospital of Hebei Medical University from January 1, 2017 to December 31, 2020 were collected. There were 312 males and 135 females, aged 60(range, 37?82)years. Observation indica-tors: (1) clinicopathological characteristics; (2) treatment; (3) follow-up; (4) analysis of prognostic factors for esophageal cancer. Follow-up using telephone interview or outpatient examination was conducted to detect survival of patients up to December 2021. The total survival time was from the surgery date to death or the last follow-up. Patients with duration of follow-up more than 2 years were included for survival and prognostic analysis. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers. Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-Rank test was used for survival analysis. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX hazard regression model. Results:(1) Clinicopathological characteristics. Of the 447 patients, 69.80%(312/447) were males and 30.20%(135/447) were females, and there were 3, 18, 101, 229, 93, 3 cases aged 30?39 years, 40?49 years, 50?59 years, 60?69 years, 70?79 years, 80?89 years, respectively. About the pathological type, there were 424 cases with squamous carcinoma, 11 cases with small cell carcinoma, 4 cases with adenosquamous carcinoma, 3 cases with sarco-matoid carcinoma, 2 cases with adenocarcinoma, 1 case with neuroendocrine carcinoma, 1 case with undifferentiated carcinoma, and 1 case with adenoid cystic carcinoma. There were 2 cases with tumor located at cervicothoracic segment, 49 cases with tumor located at upper thoracic segment, 273 cases with tumor located at mid-thoracic segment, and 123 cases with tumor located at lower thoracic segment. There were 6, 24, 74, 59, 192, 80, 12 cases in stage pT0, pT1a, pT1b, pT2, pT3, pT4a, pT4b of pathological T staging, respectively. There were 207, 63, 142, 28, 7 cases in stage pN0, pN1, pN2, pN3, pN4 of pathological N staging by Japan Esophagus Society (JES), respectively. There were 207, 128, 76, 36 cases in stage pN0, pN1, pN2, pN3 of pathological N staging by Union for International Cancer Control (UICC), respectively. About TNM staging, there were 25, 53, 127, 174, 68 cases in stage 0, Ⅰ, Ⅱ, Ⅲ, Ⅳa of JES staging, and 16, 9, 53, 35, 108, 96, 45, 85 cases in stage 0, Ⅰa, Ⅰb,Ⅱa, Ⅱb, Ⅲa, Ⅲb, Ⅲc of UICC staging, respectively. (2) Treatment. Of the 447 patients, 63 cases underwent neoadjuvant therapy(12 cases combined with immunotherapy), 384 cases underwent no neoadjuvant therapy. There were 347, 97, 2, 1 cases with surgical approach as right thoracic approach, left thoracotomy approach, cervical abdominal approach, left thoracoabdominal approach, respectively. There were 316, 5, 126 cases with surgical platform as totally endoscopic esophagec-tomy, Hybrid surgery, open surgery, respectively. There were 350 and 97 cases with digestive recons-truction as posterior mediastinal approach and intrathoracic approach, respectively. Surgical margin as R 0, R 1, R 2 resection was detected in 323, 116, 8 cases, respectively. Six of 447 patients died during the hospital stay. (3) Follow-up. All the 447 patients were followed up for 25(range, 2?48)months, including 233 cases with the follow-up more than 2 years. The median survival time of 233 patients was unreached, and the postoperative 2-year survival rate was 76.8%. (4) Analysis of prognostic factors for esophageal cancer. Results of univariate analysis showed that gender, neoadjuvant therapy, surgical margin, pT staging, pN staging by JES, pN staging by UICC, TNM staging by JES, TNM staging by UICC were related factors influencing prognosis of 233 patients with esophageal cancer ( χ2=6.62, 17.81, 32.95, 37.93, 27.06, 35.56, 45.24, 37.84, P<0.05). Results of multivariate analysis showed that gender, surgical margin, TNM staging by JES were independent factors influencing prognosis of 233 patients with esophageal cancer ( hazard ratio=0.48, 1.94, 1.46, 95% confidence intervals as 0.25?0.91, 1.07?3.52, 1.16?1.84, P<0.05). Conclusions:The incidence of esophageal cancer is relatively high in males, with the onset age mainly distribute in 60?69 years and the mainly pathological type as squamous carcinoma. Patients with esophageal cancer have advanced tumor staging, low proportion of neoadjuvant therapy, high R 0 resection rate of surgical treatment. Gender, surgical margin, TNM staging by JES are independent factors influencing prognosis of patients with esophageal cancer.

Objective:To screen and analyze the prognostic protein biomarkers of DLBCL, and to explore their value in the prognostic evaluation.Methods:163 cases of confirmed DLBCLs from January 2011 to December 2016 were collected with their clinical, pathological and follow-up data, which were all from our hospital. The expression of protein markers were tested using immunohistochemical staining (IHC) . The immune phenotypes independent of the International Prognostic Index (IPI) that affect overall survival (OS) and progression-free survival (PFS) of DLBCL were explored by COX regression model, and the effect of their co-expression on the prognosis were also analyzed.Result:BCL6 negative (PFS: HR=1.652, 95% CI 1.030-2.649, P=0.037) , P53 positive (OS: HR=1.842, 95% CI 1.008-3.367, P=0.047) , and BCL2 strong positive expressions (S+) (OS: HR=2.102, 95% CI 1.249-3.537, P=0.005; PFS: HR=2.126, 95% CI 1.312-3.443, P=0.002) are adverse prognostic factors of DLBCL that are independent of IPI. BCL6 - (PFS: HR=2.042, 95% CI 1.021-4.081, P=0.043) , P53 + (OS: HR=3.069, 95% CI 1.244-7.569, P=0.015) and BCL2 S+ (OS: HR=2.433, 95% CI 1.165-5.082, P=0.018; PFS: HR=3.209, 95% CI 1.606-6.410, P=0.001) are adverse prognostic factors in the group of age≤60-year-old; in the group of IPI score 0-2, cases with BCL6 - (OS: HR=2.467, 95% CI 1.322-4.604, P=0.005; PFS: HR=2.248, 95% CI 1.275-3.965, P=0.005) and BCL2 S+ (PFS: HR=2.045, 95% CI 1.119-3.735, P=0.020) have worse prognosis. The co-expression of BCL6 - and BCL2 S+ has significant influence on prognosis of DLBCL ( P=0.005 and P<0.001) , in which BCL6 +/non-BCL2 S+ ( n=86) has the best prognosis[3-year-OS (71.6±4.9) %, 3-year-PFS (67.0±5.1) %], and BCL6 -/BCL2 S+ ( n=10) has the worst prognosis[3-year-OS (20.0±12.6) %, 3-year-PFS (10.0±9.5) %]; the co-expression of BCL6 - and P53 + has no significant influence on prognosis ( P=0.061 and P=0.089) , however, those cases with BCL6 +/P53 - ( n=98) often get better prognosis[3-year-OS (70.6±4.7) %, 3-year-PFS (64.6±4.9) %] than others; the co-expression of P53 + and BCL2 S+ has significant influence on prognosis of DLBCL ( P<0.001 and P<0.001) , and P53 +/BCL2 S+ ( n=5) has the worst prognosis (3-year-OS and 3-year-PFS are both 0) ; BCL2 S+ cases get shorter OS and PFS, regardless of the expression of BCL6 and P53. Conclusion:The expression and co-expression of BCL6 negative, P53 positive and BCL2 S+ have certain value in the prognostic evaluation of DLBCL, especially in the group of age≤60-year-old and IPI score 0-2.