Objective To investigate the pathogenesis of the production of anti-neutrophil cytoplasmic antibodies (ANCA) in the rat models of chronic bronchitis (CB) with recurrent infections. Methods The CB models were made by double element of smoking and lipopolysaccharide (LPS) stimulation. The rats were divided into four groups, including normal control group (n=5), phorbol-12-myristate-13-acetate (PMA)-treated healthy rats control group (n=5), CB rats group (n=5) and PMA-treated CB rats group (n=6). Renal function of rats was detected. The histopathological lung and kidney tissues were observed by HE staining of paraffin section. Immunological markers, including myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA), proteinase 3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA) and citrullinated histone H3 (CitH3), were measured by enzyme-linked immune-sorbent assay (ELISA) at different time points. Correlation between CitH3 and MPO-ANCA was analyzed by the Spearman rank correlation. NETs components were further detected in lung and kidney tissue by confocal immunofluorescence and colocalization analysis. Results (1) The serum levels of CitH3 and MPO-ANCA in CB+PMA group showed an increased trend. Compared with those in the normal control group and CB rats group, the serum levels of CitH3 and MPO-ANCA in CB+PMA group increased significantly at the sixth week (both P＜0.05). Serum CitH3 levels in rats were positively correlated with serum MPO-ANCA levels (rs=0.490,P=0.024). (2) There were pathological manifestations of CB in the lung tissues of rats in CB group and CB+PMA group, and no obvious abnormalities in the lung tissues of rats in the normal control group and control group. In the rat kidney tissue of CB+PMA group, there were inflammatory cells infiltrated in the glomerular and around the renal tubules, but glomerular necrosis was not found. No obvious abnormalities were observed in the kidney tissues of rats in the normal control group, PMA-treated healthy rats control group and CB group. (3) In the lung and kidney tissues of CB+PMA group NETs could be detected by confocal immunofluorescence analysis. Conclusion CB rats with the recurrent infections can release large amounts of NETs, in which the exposure of MPO antigen will break the immune tolerance and result in the production of MPO-ANCA.

Objective: To investigate the clinicopathological features of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Methods: Five cases of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract from the Affiliated Hospital of Qingdao University from 2016 to 2019 were retrospectively reviewed. The clinical and pathological parameters were analyzed by combining clinical data and reviewing the available literature of 35 cases (34 cases abroad and 1 case in China). Results: There were 4 males and 1 female with a median age of 47 years (18-66 years). All patients had abdominal pain and constitutional symptoms including diarrhea, emaciation, intermittent mucous stool or oral and epiglottic ulcers. Endoscopic manifestations included multiple punctate congestion, erosion and ulcer at the terminal ileum and colorectum. Two cases had congestion and erosion of antrum and angle of stomach, and the lesions did not fuse and form tumors. Histologically, the lamina propria was expanded by a dense, medium to small lymphocyte infiltration, which was monomorphic, with slightly irregular nuclei without prominent nucleolus or lymphoepithelial lesions. There were admixed small amount of plasma cells and eosinophils. In 4 cases, immunohistochemistry showed the lesional cells were positive for CD3, CD8, TIA1, and negative for CD4, CD56, granzyme B and Ki-67 index was ≤10%. In situ hybridization showed that EBER was negative and clonal TCR gene rearrangement was detected. One consultation case was CD3⁺, CD5^- and Ki-67 index of 10%, although other indicators were not done. All five patients were treated with symptomatic support. In follow-up observation for 2 to 25 months, all patients were alive with the disease. Conclusions Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract is a newly classified monoclonal T-cell proliferative disease, with low incidence, clinical inertia and long-term survival. It has unique clinicopathological features but pathologically it is easily misdiagnosed as inflammatory bowel disease or T-cell lymphoma. Correct diagnosis is of great important clinical significance.

Objective To investigate the clinicopathological features of indolent T?cell lymphoproliferative disorder of the gastrointestinal tract. Methods Five cases of indolent T?cell lymphoproliferative disorder of the gastrointestinal tract from the Affiliated Hospital of Qingdao University from 2016 to 2019 were retrospectively reviewed. The clinical and pathological parameters were analyzed by combining clinical data and reviewing the available literature of 35 cases (34 cases abroad and 1 case in China). Results There were 4 males and 1 female with a median age of 47 years (18-66 years). All patients had abdominal pain and constitutional symptoms including diarrhea, emaciation, intermittent mucous stool or oral and epiglottic ulcers. Endoscopic manifestations included multiple punctate congestion, erosion and ulcer at the terminal ileum and colorectum. Two cases had congestion and erosion of antrum and angle of stomach, and the lesions did not fuse and form tumors. Histologically, the lamina propria was expanded by a dense, medium to small lymphocyte infiltration, which was monomorphic, with slightly irregular nuclei without prominent nucleolus or lymphoepithelial lesions. There were admixed small amount of plasma cells and eosinophils. In 4 cases, immunohistochemistry showed the lesional cells were positive for CD3, CD8, TIA1, and negative for CD4, CD56, granzyme B and Ki?67 index was ≤10%. In situ hybridization showed that EBER was negative and clonal TCR gene rearrangement was detected. One consultation case was CD3+, CD5-and Ki?67 index of 10%, although other indicators were not done. All five patients were treated with symptomatic support. In follow?up observation for 2 to 25 months, all patients were alive with the disease. Conclusions Indolent T?cell lymphoproliferative disorder of the gastrointestinal tract is a newly classified monoclonal T?cell proliferative disease, with low incidence, clinical inertia and long?term survival. It has unique clinicopathological features but pathologically it is easily misdiagnosed as inflammatory bowel disease or T?cell lymphoma. Correct diagnosis is of great important clinical significance.

Objective:To investigate the efficacy and safety of immune checkpoint inhibitors (ICI), programmed death receptor 1 (PD-1) inhibitors and programmed death receptor-ligand 1 (PD-L1) inhibitors in the treatment of extensive-stage small cell lung cancer (ES-SCLC).Methods:The databases of CNKI, Wanfang, VIP, China Biology Medicine disc, PubMed, Embase, and Cochrane Clinical Controlled Trial Center Registry (CENTRAL) were retrieved, and the randomized controlled trial literature on the treatment of ES-SCLC with immune checkpoint inhibitors published from the establishment of the database until October 4, 2023 were reviewed. After screening literature and extracting data according to inclusion and exclusion criteria, the risk of bias in the study was evaluated using Review Manager 5.4 software. The disease remission, prognosis and adverse events (AE) of patients treated with ICI combined with chemotherapy (experimental group) and placebo± chemotherapy (control group) in the whole group and liver metastases and brain metastases subgroups were compared.Results:A total of 11 randomized controlled trials were included, with 2 243 cases in the experimental group and 2 059 cases in the control group. The included research data were complete and showed no selective bias. Compared with the control group, the objective response rate (ORR) of patients in the experimental group was higher [control group vs. experimental group, 64% (864/1 358) vs. 70% (1 088/1 532), RR = 1.08 (95% CI: 1.03-1.14), P = 0.003], and the difference was statistically significant; progression free survival (PFS) [experimental group vs. control group, the median PFS time, 5.14 months (95% CI: 4.88-5.40 months) vs. 4.76 months (95% CI: 4.70-4.82 months), HR = 0.72 (95% CI: 0.67-0.78), P < 0.001] and overall survival (OS) [experimental group vs. control group, the median OS time, 12.89 months (95% CI: 12.18-13.60 months) vs. 10.41 months (95% CI: 10.03-10.79 months), HR = 0.72 (95% CI: 0.67-0.78), P < 0.001] were all improved, and the differences were statistically significant. The OS of patients with baseline liver metastasis in the experimental group was better than that in the control group (experimental group vs. control group, HR = 0.82 (95% CI: 0.71-0.95), P = 0.009], and the difference was statistically significant, while the difference in OS of patients with baseline brain metastases was not statistically significant between the experimental group and the control group [experimental group vs. control group, HR = 0.84 (95% CI: 0.66-1.08), P = 0.170]. The incidence of AE [experimental group vs. control group, 31% (597/1 952) (95% CI: 24%-37%) vs. 14% (255/1 762) (95% CI: 9%-22%), RR = 2.25 (95% CI: 1.67-3.02), P < 0.001] and the incidence of drug discontinuation or dose change caused by AE [experimental group vs. control group, 21% (379/1 774) (95% CI: 12%-41%) vs. 19% (307/1 588) (95% CI: 6%-25%), RR = 1.20 (95% CI: 1.07-1.33), P = 0.001] in the experimental group were higher than those in the control group, and the differences were statistically significant. However, the incidence of severe (≥grade 3) AE in both the experimental group and the control group was 34% (620/1 814, 557/1 632) (both 95% CI: 32%-36%), and the difference was not statistically significant [experimental group vs. control group, RR = 1.00 (95% CI: 0.91-1.10), P = 0.960]. The incidence of hypothyroidism [experimental group vs. control group, 11% (118/1 083) (95% CI: 9%-13%) vs. 1% (11/886) (95% CI: 0-2%), RR = 8.56 (95% CI: 4.63-15.80), P < 0.001] and the incidence of hyperthyroidism [experimental group vs. control group, 7% (75/1 083) (95% CI: 5%-8%) vs. 2% (17/886) (95% CI: 1%-4%), RR = 3.27 (95% CI: 1.95-5.46), P < 0.001] in the experimental group were both higher than those in the control group, and the differences were statistically significant. Conclusions:ICI combined with chemotherapy can effectively improve the OS, PFS and disease remission of patients with ES-SCLC, as well as improve the survival of patients with liver metastases. However, there is no benefit in the survival of patients with brain metastases. The incidence of immune-mediated AE to ICI combined with chemotherapy has increased, but the overall safety is good.

In response to calls of the state to share high quality medical resources with the primary levels for easier access of the local people to best medical care instead of pouring into tertiary hospitals in metropolitans, Xiamen city joined hands with Zhongshan Hospital of Fudan University to establish Xiamen Hospital affiliated to Zhongshan Hospital of Fudan University in an innovative model of " city-university cooperation and homogeneous management" . Open for full service in January 2018, the hospital is run by Zhongshan Hospital in a closed-type medical alliance, enjoying homogenous management in terms of administrative framework, quality of care, talent training and IT management. Thanks to this practice, the hospital has grown into one of the first pilot units of the national regional medical center program, rapidly upgrading medical service level of Xiamen city and its surrounding regions. This paper highlighted the practice of homogeneous management, and analyzed the challenges and solutions for references of building trans-regional closed-type medical alliances.

Objective:To establish an animal model of chronic systemic inflammation with long-term high expression of circulating IL-6 by introducing exogenous IL-6 gene transfer vector.Methods:Recombinant murine IL-6-encoding adeno-associated virus (AAV-IL-6) was constructed. Twenty-one 24-week-old male C57BL/6J mice were randomly divided into three groups with seven in each group: AAV-IL-6 group, vector control (AAV-ctrl) group and blank control group. At 0, 8 and 16 weeks of intervention, the mice in the three groups were injected with AAV-IL-6 (100 μl 0.5×10 10 vp/ml), unloaded AAV (100 μl 0.5×10 10 vp/ml) and the same volume of saline in the tail vein, respectively. IL-6 levels in mouse serum were measured by ELISA. The general condition of mice was observed and blood routine tests were performed. Changes in blood biochemical parameters and C-reactive protein (CRP) levels were detected. At the end of 24-week intervention, the mice were sacrificed and the myocardium, liver, spleen, quadriceps femoris, knee joint and middle femur were taken for HE staining. Results:At 4, 8, 16 and 24 weeks after intervention, serum IL-6 levels were (75.41-169.28) pg/ml in the AAV-IL-6 group, while in the two control groups, the levels were below the lower limit of detection (7.8 pg/ml). At 24 weeks after intervention, the body weight of mice in the AAV-IL-6 group was significantly lower than that of mice in the two control groups; the neutrophil counts and CRP level in the AAV-IL-6 group were higher than those in the two control groups, while the levels of albumin, creatinine, triglyceride and cholesterol were lower than those in the two control groups. There were no differences in the aforementioned parameters between the two control groups. Compared with the blank control group, both AAV-IL-6 and AAV-ctrl groups showed increased lymphocyte counts. All mice had normal liver and kidney functions at the end of intervention. Histopathological findings indicated that the mice in the AAV-IL-6 group had focal infiltration of lymphocytes in the central venous area of the liver and around the myocardial and the skeletal muscle fibers, diffuse infiltration of multinucleated giant cells in the spleen, atrophic skeletal muscle, disorganized growth plate, reduced chondrocyte hypertrophic zone, thinner bone cortex and trabecular, and reduced osteoid. There were no histopathological changes in mice of the two control groups.Conclusions:Repeated tail vein injection of AAV-IL-6 could achieve long-term high expression of circulating IL-6 in mice, which manifested the phenotype of chronic systemic inflammation in preliminary detection and provided a safe, effective and simply accessible animal model for related studies.

Objective: To systematically analyze the revisions content and technological development trends of microbiological standards in the Chinese Pharmacopoeia (ChP) 2025 Edition, and explore its novel requirements in risk-based pharmaceutical product lifecycle management.
Methods: A comprehensive review was conducted on 26 microbiological-related standards to summarize the revision directions and scientific implications from perspectives including the revision overview, international harmonization of microbiological standards, risk-based quality management system, and novel tools and methods with Chinese characteristics.
Results: The ChP 2025 edition demonstrates three prominent features in microbiological-related standards: enhanced international harmonization, introduced emerging molecular biological technologies, and established a risk-based microbiological quality control system.
Conclusion: The new edition of the Pharmacopoeia has systematically constructed a microbiological standard system, which significantly improves the scientificity, standardization and applicability of the standards, providing a crucial support for advancing the microbiological quality control in pharmaceutical industries of China.

Objective:To investigate the clinicopathological characteristics of the T cell lymphomas with CD20 expression, and to better understand this rare entity.Methods:Two-hundred cases of T-cell lymphoma diagnosed in the Department of Pathology of the Affiliated Hospital of Qingdao University from November 2016 to February 2020 were examined, and 5 cases of CD20-positive T-cell lymphomas were identified and included. Combined with clinical data and review of the literature, the clinicopathological characteristics of the disease were analyzed.Results:The five patients were all male, and had an average age of 56 years (range, 47 to 64 years). There were 2 cases of monomorphic epitheliotropic intestinal T-cell lymphoma, 2 cases of mycosis fungoides (1 case was plaque stage and the other was tumor stage) and 1 case of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Immunohistochemistry showed that all 5 cases expressed multiple T cell markers (CD3/CD4/CD5/CD7/CD8) and only one of B cell markers (CD20). Three of the 5 cases were negative for CD20 at the first diagnosis, while CD20 was diffusely positive on the second biopsy from the recurrence or progression of the disease, without expression of CD79a or PAX5. Epstein-Barr encoding region (EBER) in situ hybridization was negative in all 5 cases. T-cell receptor gene analysis showed monoclonal rearrangement of β or/and δ chains;Ig rearrangements were all polyclonal. None of the five patients were treated with rituximab, and 4 patients survived with disease and 1 patient survived without disease at the end of follow-up. Among them, the patient with mycosis fungoides at the cancerous stage has progressed rapidly and had poor quality of life.Conclusions:CD20-positive T-cell lymphoma is extremely rare. Its prognosis is closely related to the type of T-cell lymphoma, clinical stage and initial therapeutic effect. However, the expression of CD20 indicates the recurrence or progression of the disease, and the prognosis is relatively poor. When CD3 expression is absent in T-cell lymphoma, it is easy to be misdiagnosed as B-cell lymphoma. The combination of multiple immunohistochemical antibodies and molecular detection can improve the accuracy of diagnosis.

Discipline construction is the main focus of the high-quality development of public hospitals. The authors elaborated on the practice of Zhongshan Hospital(Xiamen), Fudan University, based on the " double-center" homogenization management, implementing the 123456 strategy of " integrated management and homogeneous development" in discipline construction. The hospital has promoted discipline construction from six aspects: building discipline cluster, promoting talent cultivation, building science and technology innovation platform, precise personnel classification, medical and education collaborative education, and information sharing and support. It has achieved new development goals of filling weak discipline gaps, transforming talent transfusion into hematopoietic, and integrating medical, educational, research and management innovation. However, it also encountered difficulties such as homogenization barrier of discipline construction, shortage of excellent talents, and limited brand influence of superior disciplines. The authors put forward suggestions from three dimensions: deepening homogeneous management, building talent echelon, and increasing publicity, in order to provide experience for the high-quality development of other hospitals.

OBJECTIVETo investigate the relationship between extranodal tumor deposits and prognosis in patients with colorectal cancer.

METHODSThe literatures on extranodal tumor deposits and postoperative survival rate in patients with colorectal cancer published at home and abroad from 1990 to 2014 were retrieved in 15 English literature databases such as MEDLINE/PubMed, Web of Science, Directory of Open Access Journals(DOAJ), SpringerLink and Chinese literature databases such as Chinese Biomedical Literature Database CD-ROM, China National Knowledge Infrastructure (CNKI) Database with the internet platform of Yonsei University Library. After screening for inclusion, data extraction and quality assessment, meta-analysis was conducted by the Review Manager 5.3 software.

RESULTSThere were 10 studies meeting the inclusion criteria for meta-analysis. The total sample size of the studies was 4 068 cases with ENTD(+) 727 cases, while ENTD(-) 3 341 cases. Meta analysis showed that 5-year overall survival rate and 5-year relapse-free survival rate were significantly lower in ENTD(+) group than those in ENTD(-) group (OR 0.27, 0.23; 95% CI:0.18 to 0.43, 0.16 to 0.34 respectively, both P=0.000); the 5-year overall survival rates were both significantly lower in ENTD(+) group as compared to ENTD(-) group for patients with N0 and N(+) colorectal cancer (both P<0.05).

CONCLUSIONExtranodal tumor deposits is a poor prognostic factor of patients with colorectal cancer.