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.

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 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.

Lymphoma refers to a group of heterogeneous malignancies originating from the reticuloendothelial and lymphatic systems. The clinical manifestations, treatment strategies, and disease outcomes of different types of lymphoma considerably vary. Recent developments in high-throughput sequencing technologies have enhanced understanding of the pathogenesis and molecular stratification of lymphoma. In the era of new drugs, precise stratification and targeted drug selection can not only improve the prognosis of patients with lymphoma but also reduce the toxic side effects of traditional chemotherapy, ultimately achieving the accurate diagnosis and individualized treatment of tumors. This article reviews the research progress of molecular diagnosis and individualized treatment of different lymphoma subtypes and lymphoma-related research in important meetings such as ASCO, EHA, and ICML in 2023.

Objective:To understand the performance of public health risk assessment in emergencies of institutions for disease control and prevention at different levels in China, and provide suggestions for the improvement of public health risk assessment.Methods:A self-administered survey was conducted in professionals involved in public health risk assessment in emergencies from national institution, provincial institutions and some prefectural institutions for disease control and prevention (1-2 prefectural institutions were selected using convenience sampling in each province) between March and April in 2021.Results:A total of 79 institutions for disease control and prevention were investigated, including 1 national institution, 32 provincial institutions and 46 prefectural institutions. By April 2021, all the 79 institutions surveyed had conducted risk assessment of public health emergencies, in which 61 (77.2%) had established departments responsible for the public health risk assessment, i.e. emergency management office or communicable disease prevention and control office (section), and regular risk assessment mechanisms. The main sources of information for public health risk assessment were public health surveillance systems, including the National Notifiable Diseases Reporting System (100.0%) and Public Health Emergencies Management Information System (97.5%). Compared with the provincial institutions, the prefectural institutions were more likely to use specific disease surveillance systems (84.8% vs. 62.5%; χ2=5.09, P=0.024). The risk management recommendations made by 43 institutions for disease control and prevention (54.4%) after the risk assessment were accepted by the superior health administrative departments and used in epidemic prevention and control. Conclusions:Public health risk assessment in emergencies has been widely carried out by national, provincial and prefectural institutions for disease control and prevention in China. Specialized departments and mechanisms have been established, but the information sources are still confined to public health surveillance systems and the application of the risk assessment results still needs to be further improved.

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.

Objective:To investigate the application value of different surgical approaches in the radical resection of Siewert type Ⅱ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective cohort study was conducted. The clinicopathological data of 84 patients with Siewert Ⅱ AEG who were admitted to the Fourth Hospital of Hebei Medical University from March 2018 to March 2019 were collected. There were 65 males and 19 females, aged from 43 to 82 years, with a median age of 66 years. Of 84 patients, 24 cases undergoing radical resection of AEG via abdominal transhiatal approach (TH) were allocated into TH group, 32 cases undergoing radical resection of AEG via left thoracic approach (Sweet) were allocated into Sweet group, 28 cases undergoing radical resection of AEG via right thoracoabdominal approach (RTA) were allocated into RTA group. Observation indicators: (1) surgical and postoperative conditions of Siewert Ⅱ AEG patients in the 3 groups; (2) postoperative complications of Siewert Ⅱ AEG patients in the 3 groups. (3) Follow-up. Follow-up using outpatient examination and telephone interview was conducted to detect postoperative life quality, tumor recurrence and survival of patients up to March 2020. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the ANOVA. Measurement data with skewed distribution were represented as M (range), comparison among multiple groups was analyzed using the Kruskal-Wallis H test, and comparison between two groups was analyzed using the Dunn Bonferroni test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Results:(1) Surgical and postoperative conditions of Siewert Ⅱ AEG patients in the 3 groups: the operation time for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 216 minutes (range, 190-230 minutes), 174 minutes (range, 152-185 minutes) and 295 minutes (range, 261-337 minutes), respectively, showing a significant difference among the 3 groups ( H=57.977, P<0.05). There were significant differences between the TH group and the Sweet group, between the TH group and the RTA group, respectively ( P<0.05). There was also a significant difference between the Sweet group and the RTA group ( P<0.05). The volume of intraoperative blood loss for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 150 mL (range, 100-163 mL), 150 mL (range, 150-200 mL) and 200 mL (range, 150-263 mL), respectively, showing a significant difference among the 3 groups ( H=11.097, P<0.05). There was no significant difference between the TH group and the Sweet group ( P>0.05). There were significant differences between the TH group and the RTA group, between the Sweet group and the RTA group, respectively ( P<0.05). The number of lymph node dissected for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 15 (range, 9-19), 17 (range, 10-21) and 30 (range, 24-40), respectively, showing a significant difference among the 3 groups ( H=29.775, P<0.05). There was no significant difference between the TH group and the Sweet group ( P>0.05). There were significant differences between the TH group and the RTA group, between the Sweet group and the RTA group, respectively ( P<0.05). The number of thoracic lymph node dissected for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 0, 2 (range, 1-3) and 6 (range, 3-9), respec-tively, showing a significant difference among the 3 groups ( H=48.140, P<0.05). There were significant differences between the TH group and the Sweet group, between the TH group and the RTA group, respectively ( P<0.05). There was also a significant difference between the Sweet group and the RTA group ( P<0.05). The number of abdominal lymph node dissected for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 15 (range, 9-19), 12 (range, 8-19), and 24 (range, 17-35), respectively, showing a significant difference among the 3 groups ( H=18.149, P<0.05). There was no significant difference between the TH group and the Sweet group ( P>0.05). There were significant differences between the TH group and the RTA group, between the Sweet group and the RTA group, respectively ( P<0.05). The number of positive lymph node for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 2 (range, 0-3), 0 (range, 0-3), and 5 (range, 1-6), respectively, showing a significant difference among the 3 groups ( H=7.729, P<0.05). There was no significant difference between the TH group and the Sweet group, between the TH group and the RTA group, respectively ( P>0.05). There was a significant difference between the Sweet group and the RTA group ( P<0.05). The time to postoperative first flatus of Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 3 days (range, 3-4 days), 3 days (range, 3-4 days), and 4 days (range, 3-5 days), respectively, showing no significant difference among the 3 groups ( H=3.125, P>0.05). The duration of postoperative hospital stay for Siewert type Ⅱ AEG patients in TH group, Sweet group and RTA group were 16 days (range, 14-17 days), 14 days (range, 12-15 days), and 19 days (range, 18-21 days), respectively, showing a significant difference among the 3 groups ( H=35.244, P<0.05). There was no significant difference between the TH group and the Sweet group ( P>0.05). There were significant differences between the TH group and the RTA group, between the Sweet group and the RTA group, respectively ( P<0.05). (2) Postoperative complications of Siewert Ⅱ AEG patients in the 3 groups: there were 6, 6, 11 Siewert type Ⅱ AEG patients of the TH group, Sweet group and RTA group with cardiopulmonary complication, respectively, 1, 1, 2 patients with anastomotic leakage and 1, 0, 1 patients with AEG-related death, showing no significant difference in the above indicators among the 3 groups ( χ2=3.263, 0.754, 1.595, P>0.05). (3) Follow-up: 78 of 84 Siewert type Ⅱ AEG patients were followed up for 9.0 to 24.0 months, with a median follow-up time of 16.6 months. Cases with reduced respiratory function at postoperative 3 months for the TH group, Sweet group and RTA group were 4, 3, 5, respectively. Cases with gastroesophageal reflux at postoperative 3 months for the 3 groups were 3, 6, 7, respectively. Cases with weight loss at post-operative 3 months for the 3 groups were 3, 2, 4, respectively. There was no significant difference in the above indicators among the 3 groups ( χ2=1.009, 1.107, 1.112, P>0.05). Cases tumor recurrence and metastasis in the TH group, Sweet group and RTA group were 5, 7, 4, cases who survived at postoperative 1 year in the 3 groups were 19, 24, 25, respectively. There was no significant difference in the above indicators among the 3 groups ( χ2=0.897, 1.261, P>0.05). Conclusion:RTA appiled in Siewert type Ⅱ AEG patients has a longer postoperative operation time, increased intra-operative blood loss and longer hospital stay, while has better advantages in lymph node dissection.

OBJECTIVE： To mine and evaluate the post-marketing safety alert signals of pegaspargase （PEG-ASP） and L-asparaginase （L-ASP），and compare the safety differences between them ，so as to provide reference for clinical safe and rational drug use. METHODS ： The adverse drug event （ADE） reports of PEG-ASP and L-ASP issued by FDA adverse event reporting system from Jan. 1st，2004-Jun. 30th，2020 were retrieved. BCPNN method was used to mine the safety signals of these two drugs under the condition that the lower limit of information component （IC－2SD）＞0 and the number of events ≥3. The medium and strong signals of two drugs with IC －2SD≥1.5 were evaluated and compared in 8 system organ class，such as gastrointestinal system ，hepatobiliary system ，blood and lymphatic system ，blood vessels and lymphatic vessels ， nervous system ，immune system ，metabolism and nutrition ，various examinations. IC value of specific ADE signal and its 95％ confidence interval were analyzed by time scanning spectrum. RESULTS & CONCLUSIONS ：The reports of PEG-ASP and L-ASP as suspected drugs were 2 324 and 3 824；67 and 68 medium and strong signals were included ，respectively. In gastrointestinal system，the common strong signal of PEG-ASP and L-ASP was necrotic pancreatitis. In hepatobiliary system ，both of them showed strong signal in venoocclusive liver disease ，and this ADE was not included in the drug instruction. In blood and lymphatic system ， common strong signals of the two drugs were febrile neutropenia ，coagulation disorder ，neutropenia and febrile bone marrow regeneration disorder ；in blood vessels and lymphatic vessels ，in addition to haemodynamic instability ，IC values of other signals of L-ASP were higher than those of PEG-ASP. In nervous system ，IC values of other signals of L-ASP were higher than those of PEG-ASP except for intracranial haemorrhage. In immune system ，anaphylactic reaction was a medium signal for L-ASP but was a strong signal for PEG-ASP. In metabolism and nutritional diseases ，except for tumor lysis syndrome ，IC values of other signals of L-ASP were higher than those of PEG-ASP. The results of time scanning spectrum showed that the signals of necrotic pancreatitis and coagulation disorder of PEG-ASP were stable ，while the signals of veno occlusive liver disease and hypersensitivity were unstable and needed to be observed ；above four signals of L-ASP were stable signals. When using PEG-ASP or L-ASP clinically ， close attention should be paid to the safety problems such as hypersensitivity ，coagulation disorder ，thrombosis，necrotic pancreatitis，venoocclusive liver disease and hypoproteinemia.