The chronicity of infectious diseases is an important field in the collaborative research of traditional Chinese and Western medicine. The warm disease theory of pathogen invading nutrient and blood aspects in traditional Chinese medicine （TCM） takes the struggle between healthy Qi and pathogenic Qi and cementation of Yin as the core pathogenesis， providing a unique theoretical framework for explaining the common pathology of infectious chronic diseases. This theory originated from Yin-Yang interaction in the Internal Classic and was enriched with WU Youke's theory of intruding pathogen interacting and lingering in blood vessels and YE Tianshi's theory of long-term illness entering collaterals. Combining the theory with modern medical knowledge， our team has condensed the dynamic pathogenesis model of deficiency （nutrient and blood aspects） and excess （pathogen） interacting in the blood collaterals of Yin aspect， the core feature of which is the four-dimensional interactions of cause （pathogen characteristics）， location （three Yin locations of diseases）， nature （deficiency and excess）， and potential （transmission trend）. The common pathology of infectious chronic diseases is reflected in interactions. That is， the interactions between nutrient and blood deficiency （immune exhaustion and metabolic disorder） and pathogen excess （pathogen persistence and fibrous hyperplasia） in the liver collaterals （Jueyin）， kidney collaterals （Shaoyin）， lung collaterals （Taiyin） and other blood collaterals of Yin aspect form the pathological damage characterized by immune inflammatory response-continuous tissue damage with excessive repair. Taking the inheritance and innovative development of classics as the main line， this paper systematically discusses the scientific connotation of the theory of pathogen invading nutrient and blood aspects and the paths of inheritance and innovation and clarifies the original significance of this theory in the chronic development of infectious diseases. Furthermore， taking clinical diseases as an example， this paper reflects the guiding value of this classical theory in the modern diagnosis and treatment of infectious diseases with integrated traditional Chinese and Western medicine and the application potential of this theory in solving complex medical problems through the construction of the innovative paradigm of precise diagnosis and treatment with integrated traditional Chinese and Western medicine.

Objective To observe the value of AcoStream thrombus aspiration catheter for treating intermediate-high risk acute pulmonary embolism(APE).Methods Twenty-six patients with intermediate-high risk APE who underwent treatment with AcoStream thrombus aspiration catheter were retrospectively collected.The immediate technical success rate,procedure success rate and thrombus clearance rate of target vessels were recorded,as well as clinical success rate and complications in perioperative period and the recurrence of pulmonary embolism(PE)during follow-up.Results Among 26 patients with intermediate-high risk APE,the immediate technical success rate was 100%(26/26),the procedure success rate was 92.31%(24/26),and the immediate thrombus clearance rate of target vessels was 63.37%as median,including 16 cases(16/26,61.54%)achieved thrombus clearance rate grade Ⅱ or above.The perioperative period clinical success rate of treating intermediate-high risk APE was 96.15%(25/26).Two patients experienced transient arrhythmia and other 2 patients experienced worsening transient chest tightness during the procedure,and 1 case developed hematoma at the puncture site after treatment.During follow-up,no recurrence of symptomatic PE was observed.Conclusion AcoStream thrombus aspiration catheter was safe and effective for treating intermediate-high risk APE,worthy clinical promotion and application.

Objective To observe the value of AcoStream thrombus aspiration catheter for treating intermediate-high risk acute pulmonary embolism(APE).Methods Twenty-six patients with intermediate-high risk APE who underwent treatment with AcoStream thrombus aspiration catheter were retrospectively collected.The immediate technical success rate,procedure success rate and thrombus clearance rate of target vessels were recorded,as well as clinical success rate and complications in perioperative period and the recurrence of pulmonary embolism(PE)during follow-up.Results Among 26 patients with intermediate-high risk APE,the immediate technical success rate was 100%(26/26),the procedure success rate was 92.31%(24/26),and the immediate thrombus clearance rate of target vessels was 63.37%as median,including 16 cases(16/26,61.54%)achieved thrombus clearance rate grade Ⅱ or above.The perioperative period clinical success rate of treating intermediate-high risk APE was 96.15%(25/26).Two patients experienced transient arrhythmia and other 2 patients experienced worsening transient chest tightness during the procedure,and 1 case developed hematoma at the puncture site after treatment.During follow-up,no recurrence of symptomatic PE was observed.Conclusion AcoStream thrombus aspiration catheter was safe and effective for treating intermediate-high risk APE,worthy clinical promotion and application.

Low dose radiation (LDR) is a relatively low dose, but it is important in the fields of occupational health, medical radiation protection and environmental protection. Therefore, the effects of LDR on DNA damage repair and its potential mechanisms have attracted increasing attention. LDR mainly acts on DNA molecules in direct or indirect ways, leading to DNA double strand breaks (DSBs), which then triggers DNA damage, forms cluster damage, and induces DNA damage repair, which has a potential impact on organisms. However, long-term LDR exposure may lead to dysfunction of the DNA repair system and increase the risk of accumulating DNA damage. LDR-induced DNA damage response is an adaptive response, with DNA damage repair being one of its main mechanisms. The repair of DSBs is particularly important, with the main repair methods including homologous recombination and non-homologous end joining. LDR may also trigger adaptive responses by activating immune cells, enhancing cellular antioxidant capacities, and through varies of specific biological mechanisms such as immune/inflammatory response and antioxidant responses. The biological effects of LDR mainly include cell stress response, cell cycle regulation and bystander effect. In the future, it is necessary to further explore the molecular mechanism of LDR's impact on organism health and evaluate its impact on radiation risk assessment and individualized protective measures, to better understand the basic principles of radiation biology and provide scientific basis for radiation protection, risk assessment and injury treatment.

Objective To analyze and set up the effective dose of different ionizing radiation for tunnel construction workers. Methods A total of five tunnels constructed using drilling and blasting methods were selected as the research subjects using the convenient sampling method. The workplace γ radiation effective dose, radon concentrations, and radioactive activity concentrations were detected, and on-site surveys were conducted to estimate the internal and external irradiation doses and total effective doses for workers in different work sites. Results Radiological hazards in tunnels constructed using drilling and blasting methods included radon and its progeny, γ radiation, radioactive dust (uranium-238, radium-226, thorium-232, and potassium-40) and others. The average total effective dose of ionizing radiation exposure for tunnel construction workers was (6.730 1±1.541 1) mSv. The average dose of radon and its progeny was (6.163 0±1.512 8) mSv, radioactive dust was (0.014 6±0.009 1) mSv, γ radiation was (0.552 6±0.138 7) mSv. The dose of radioactive dust of radon and its progeny was 0.24%. Radon and its progeny contributed more to the radioactive dose than radioactive dust and γ radiation (all P<0.05). Among all the radioactive dusts, the dose contribution ranked from highest to lowest was thorium-232, uranium-238, and radium-226. Conclusion For tunnel construction workers, the largest contribution to the effective dose of ionizing radiation exposure is from radon and its progeny for internal irradiation, followed by γ radiation for external irradiation. The contribution of radioactive dust to internal irradiation dose can be considered negligible.

Objective:To examine the expression of OUT domain deubiquitinase with linear linkage specificity(OTULIN)in gastric cancer tissues and explore the impact of OTULIN silencing on the proliferation of gastric cancer MKN45 and AGS cells as well as its underlying mechanisms. Methods:Immunohistochemical staining was performed to detect the expression level of OTULIN in 73 gastric cancer tissues and 24 normal gastric mucosa.The association between OTULIN expression and the prognosis as well as the clinicopathological features of gastric cancer patients was analyzed.The above results were validated using public data from The Cancer Genome Atlas(TCGA)database and Gene Expression Omnibus(GEO)database.CRISPR/Cas9 gene editing technology was used to construct OTULIN-knockout gastric cancer cells MKN45 and AGS.The efficiency of gene knockout was validated by Western blotting.The effects of OTULIN knockout on the proliferation of gastric cancer cells MKN45 and AGS were assessed by CCK-8 assay and soft agar colony formation assay.Immunoprecipitation-mass spectrometry technique was exploited to identify potential protein substrates interacting with OTULIN and linear ubiquitin molecule INT-Ub.7KR.The changes in the activity of rate-limiting enzymes for glycolysis were measured using pyruvate kinase(PK)activity assay kit and lactate production was analyzed by lactate colorimetric/fluorometric assay kit in OTULIN-depleted cells.The effect of OTULIN on substrate linear ubiquitination was evaluated using co-immunoprecipitation and Western blotting. Results:The expression level of OTULIN in gastric cancer tissues was higher than that in normal gastric mucosa(P=0.004 1)as revealed by immunohistochemical analysis.Patients with higher OTULIN expression in the cancer tissues had a lower suvival time(P=0.007 7).Analysis of datasets from TCGA and GEO databases also confirmed that OTULIN was highly expressed in gastric tissues(P＜0.05)and high OTULIN expression was associated with poor prognosis(P=0.011).Statistical analysis also showed that higher expression of OTULIN was correlated with later TNM stages(P=0.027 3)and was an independent indicator for shorter survival time of gastric cancer patients(P=0.04).Knockout of OTULIN significantly inhibited the proliferation(P＜0.000 1),decreased the activity of PK(P＜0.01)and reduced lactate production(P＜0.01)of gastric cancer cells.OTULIN interacted with several key enzymes in the glycolysis pathway and downregulated the linear ubiquitination levels of these enzymes,including pyruvate kinase M1(PKM1),PKM2,lactate dehydrogenase A(LDHA)and LDHB. Conclusion:OTULIN is a novel biomarker for predicting the prognosis of gastric cancer patients.It activates the glycolytic pathway and promote the progression of gastric cancer possibly by downregulating the linear ubiquitination modification of rate-limiting enzymes in glycolysis.

Objective:To investigate the efficacy and safety of ixazomib-based therapy for multiple myeloma.Methods:The data of 32 patients with multiple myeloma treated with isazomib-based regimen in the Affiliated Hospital of Jining Medical University from December 2020 to December 2021 were retrospectively analyzed. Among 32 patients, 17 cases were relapsed/refractory, and the remaining 15 cases had initial treatment. The treatment regimens included ID (isazomib + dexamethasone), IRD (isazomib + lenalidomide + dexamethasone) and ICD (isazomib + cyclophosphamide + dexamethasone). The short-term curative effect and adverse reactions of relapsed/refractory patients and patients at initial onset were analyzed.Results:The overall response rate (ORR) of relapsed/refractory patients was 52.9% (9/17), of which 6 cases achieved complete remission (CR), 2 cases achieved very good partial remission (VGPR) and 1 case achieved partial remission (PR). The ORR of refractory patients receiving bortezomib therapy was 40.0% (4/10). The ORR of patients at initial onset who could be evaluated the curative effect was 100.0% (14/14), including 9 cases of CR, 2 cases of VGPR and 3 cases of PR. After treatment, 2 patients (6.2%) had grade Ⅲ-Ⅳ adverse events (1 case of herpes zoster and 1 case of thrombocytopenia), and none of the patients had grade Ⅲ-Ⅳ peripheral neuropathy.Conclusion:Isazomib is effective and safe in the treatment of initially treated and relapsed/refractory multiple myeloma.

Objective:To investigate the clinical efficacy of autologous peripheral blood hematopoietic stem cell transplantation (HSCT) in treatment of lymphoma.Methods:The clinical data of 41 lymphoma patients undergoing autologous peripheral blood HSCT at the Affiliated Hospital of Jining Medical University between January 2014 to December 2020 were retrospectively analyzed. There were 6 cases of Hodgkin lymphoma and 35 cases of non-Hodgkin lymphoma. The mobilization regimens included chemotherapy drugs + granulocyte colony-stimulating factor (G-CSF) + thrombopoietin (TPO) or chemotherapy drugs + G-CSF. The pre-conditioning schemes before transplantation were listed as follows: BEAM (mustine + cytarabine + etoposide + melphalan) regimen + decitabine in 26 patients, BEAM regimen in 12 patients, BEAM regimen + chidamide in 3 patients. The progression-free survival (PFS), overall survival (OS), related complications, prognoses after transplantation were observed. The effects of clinical staging, B symptom,International Prognostic Score Index (IPI), extranodal involved sites, hemoglobin (Hb), lactic dehydrogenase (LDH), β 2-microglobulin (β 2-MG), transplantation regimen and the status before transplantation on PFS and OS after transplantation were evaluated. Results:Among 41 patients, 37 patients (90.24%) achieved complete remission (CR), 2 patients (4.88%) achieved partial remission (PR) and 2 patients loss assessment data (4.88%) before autologous peripheral blood HSCT. The median karyocyte count was 12.74×10 8 /kg [(3.91-22.68)×10 8/kg] in 24 patients with the complete data of stem cell collection, the median CD34 positive cell count was 6.74×10 6/kg [(0.91-50.47)×10 6/kg]. All 41 patients had hematologic reconstruction. The median time of platelet implantation was 11 d (7-32 d) and the median time of granulocyte implantation was 9 d (8-16 d). All patients achieved CR after transplantation and no one case had transplantation-related death. By the end of follow-up, 33 cases (80.49%) had no progression of disease, 8 cases (19.51%) died. The OS rates of 12-month, 24-month and 72-month were 93.4%, 85.3% and 60.9%, respectively after transplantation. The PFS rates of 12-month, 24-month and 72 month were 93.3%, 84.0% and 84.0%, respectively. Median PFS and OS had not been reached. There were no statistically significant differences in the PFS and OS of patients with different gender, clinical staging, B symptom, IPI score, extranodal involved sites, Hb, LDH, β 2-MG and the status before transplantation(all P > 0.05) . The PFS and OS of patients receiving BEAM regimen + decitabine were better than those of patients receiving BEAM regimen alone (all P < 0.05). Conclusions:Autologous peripheral blood HSCT is effective in treatment of lymphoma. Moreover, BEAM regimen + dicitabine preconditioning regimen can achieve longer survival time compared with BEAM regimen alone.

Clostridioides difficile is a key pathogen of antibiotic related diarrhea and hospital associated infection, causing several outbreaks in Europe and North Americans and resulting in severe disease burden. However, the standardized diagnostic principle and detection specifications in C. difficile infection (CDI) survey are limited in China, and the infection rate and disease burden of CDI in China are unclear. Therefore, National Institute for Communicable Disease Control and Prevention,National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, together with another 11 institutions, draft the group standard entitled "Diagnosis of Clostridium difficile infection (T/CPMA 008-2020)" of Chinese Preventive Medicine Association. Based on the principle of "legality, scientificity, advancement, and feasibility", this standard clarifies risk factors, diagnosis principles, diagnoses and differential diagnoses in order to improve the accuracy of CDI diagnosis in clinical practice, guide the surveillance for CDI, and understand the infection rate and disease burden of CDI in China .

Objective To investigate the expression of Notch receptors and its relationship with clinicopathological features and prognosis in gastric cancer tissues. Methods Immunohistochemical SP method was used to detect the expression levels of Notch1, Notch2, Notch3 and Notch4 corresponding receptors in 45 patients with gastric cancer from January 2014 to May 2015 in the Third Affiliated Hospital of Hunan University of Traditional Chinese Medicine. The correlation between expression levels of Notch receptors and lymph node metastasis, TNM staging, disease-free survival (DFS) and overall survival (OS) were analyzed. Results Notch1, Notch2, Notch3 and Notch4 corresponding receptors were mainly distributed in the cytoplasm, and the positive expression rates in gastric cancer tissues were 93.3％ (42/45), 86.7％ (39/45), 80.0％ (36/45), and 77.8％ (35/45), which were higher than those in adjacent tissues [31.1％ (14/45), 24.4％(11/45), 40.0％ (18/45), and 46.7％ (21/45)], and the differences were statistically significant (all P< 0.05). There was no correlation between the expression of Notch1, Notch2, Notch3 and Notch4 corresponding receptors and lymph node metastasis, TNM staging, DFS and OS in gastric cancer tissues (all P> 0.05). Conclusion Notch receptors are highly expressed in gastric cancer tissues, and have no correlation with lymph node metastasis, TNM staging, DFS and OS of patients after surgery.