Objective:To evaluate clinical prognosis and prognostic factors of patients with early stage (Ⅰ stage) and locally advanced (Ⅱ/Ⅲ stage) lung cancer treated with carbon ion radiotherapy (CIRT).Methods:Clinical data, treatment, adverse reactions, survival and so on of 54 lung cancer patients who received CIRT and follow-up in the Heavy Ion Center of Wuwei Cancer Hospital of Gansu Province from March 2020 to September 2022 were retrospectively analyzed. The survival curve was plotted using Kaplan-Meier method. Difference tests were performed using log-rank test. Logistic regression analysis was used to identify prognostic factors.Results:According to inclusion and exclusion criteria, 54 patients were enrolled in the study, including 10 patients with early stage lung cancer and 44 patients with locally advanced lung cancer. The median follow-up time for 10 patients with early stage lung cancer was 11.0 (6.75, 17.25) months, and the median dose of irradiation was 60 Gy [relative biological effect (RBE)]. Upon the last follow-up, 3 patients had complete response (CR) and 3 patients had partial response (PR). Four patients had stable disease (SD) and no progressive disease (PD). The 1-year and 2-year local control rates (LCR), progression-free survival (PFS) rates and overall survival (OS) rates were 100%. During treatment and follow-up, 2 patients developed grade 1 radiation pneumonia, 1 case of grade 2 radiation pneumonia, 1 case of chest wall injury (chest wall pain), and there were no adverse reactions greater than grade 2. The median follow-up time of 44 patients with locally advanced stage was 12.5 (4.25, 21.75) months, and the median irradiation dose was 72 Gy (RBE). Thirty-two (73%) patients received concurrent chemotherapy during treatment, 20 (45%) patients received sequential chemotherapy after treatment, 14 (32%) patients received immune maintenance therapy and 3 (7%) patients obtained PD and received targeted drugs. Upon the last follow-up, 3 (7%) patients had CR, 17 (39%) patients had PR, 19 (43%) patients obtained SD, and 5 (11%) patients had PD. The 1-year and 2-year LCR were 96.0% and 87.3%, 90.9% and 84.1% for the 1-year and 2-year PFS rates, and 93.2% and 86.4% for the 1-year and 2-year OS rates, respectively. The median OS and PFS of patients were not reached. Multivariate logistic regression analysis showed that maintenance therapy after radiotherapy ( P=0.027) and clinical target volume (CTV) irradiation volume ( P=0.028) were the factors affecting PFS. Simultaneous chemoradiotherapy ( P=0.042) and maintenance therapy after radiotherapy ( P=0.020) were the factors affecting OS. And gross tumor volume (GTV) ≥215 ml ( P=0.068) might be an independent risk factor for grade 2 and above radiation pneumonia. Conclusions:The domestic carbon ion system has definite clinical effect and controllable toxic and side effects in the treatment of early stage and locally advanced lung cancer. The combination of synchronous chemotherapy and further maintenance treatment can significantly improve clinical prognosis of patients without significantly increasing the risk of toxic and side effects.

Teaching clinics represent a unique form of outpatient training of resident physicians and serve as a crucial instrument and core component of standardized training of general practice residents. This article reviews the common model and innovations of teaching clinics of general practice in China, and analyzes their reported effectiveness in enhancing the capabilities of consultation of resident physicians, the teaching capabilities of general practice trainers, as well as satisfaction levels of involved participants. It outlines the challenges encountered in implementing teaching clinics, including inadequate teaching facilities and equipment, incomplete incentive system for teaching, difficulties in patient recruitment, and weaknesses in the teaching capabilities of trainers. To address these challenges, this article proposes corresponding strategies based on realistic needs, including the improvement of facilities and equipment in teaching clinics, the establishment of incentive systems for teaching clinics, the expansion of patient recruitment channels for teaching clinics, and the enhancement of training for trainers' teaching capabilities. This is envisaged to provide both theoretical bases and practical guidance for the effective execution and standardized development of teaching clinics in general practice residency training bases.

Objective:To compare the adverse reactions, efficacy and survival rate of carbon ion beam irradiation in the elective lymph node (ENI) drainage area of locally advanced non-small cell lung cancer (LA-NSCLC) with relative biological effect (RBE) dose of 48 Gy using 16 and 12 fractions.Methods:A total of 72 patients with pathologically confirmed LA-NSCLC admitted to Wuwei Heavy Ion Center of Gansu Wuwei Tumor Hospital from June 2020 to December 2021 were enrolled and simple randomly divided into groups A and B, with 36 patients in each group. Patients in groups A and B were treated with carbon ion beam irradiation to the lymph node drainage area with 48 Gy (RBE) using 16 and 12 fractions. The acute and chronic adverse reactions, efficacy and survival rate were observed. The survival curve was drawn by Kaplan-Meier method. Difference test was conducted by log-rank test.Results:The median follow-up time was 13.9 (8.8-15.7) months in group A and 14.6 (6.3-15.9) months in group B. Sixteen (44.4%) patients were effectively treated in group A and 9 (25%) patients in group B. Thirty-four (94.4%) cases achieved disease control in group A and 30 (83.3%) cases in group B. Statistical analysis showed that the overall survival rate in group B was similar to that in group A ( χ2=1.192, P=0.275). Comparison of planning parameters between two groups showed CTV volume, D mean, V 5 Gy(RBE), V 20 Gy(RBE) and V 30 Gy(RBE) of the affected lung, cardiac V 20 Gy(RBE), V 30 Gy(RBE) and D mean, esophageal V 30 Gy(RBE), V 50 Gy(RBE), D max and D mean, D max of the trachea and spinal cord had no significant difference (all P>0.05). No grade 3 or 4 adverse reactions occurred in the enrolled patients during treatment and follow-up. No statistical differences were observed in the acute radiation skin reaction ( χ2=5.134, P=0.077), radiation esophagitis ( χ2=1.984, P=0.371), and advanced radiation pneumonia ( χ2=6.185, P=0.103) between two groups. Conclusions:The two dose fractionation modes of carbon ion therapy system are equally safe in the mediastinal lymphatic drainage area of LA-NSCLC, and the adverse reactions are controllable. The long-term efficacy still needs further observation.

In recent years, a number of policies have been implemented to strengthen the cultivation of general practitioners in China. However, the development of community-level health professionals is still lagging behind, the development is uneven among regions, the overall number of general practitioners is insufficient, and the quality of medical services needs to be improved. Based on the Shanhai (Mountain and Sea) promotion project, with the close cooperation between the Second Affiliated Hospital and the medical consortium unit Suichang County People′s Hospital, a " Joint Cultivation by Dual-Teachers " model has been applied in training general practitioners for Suichang county community since March 2021. In this article we discuss the optimization and integration of medical and health resources through the outreaching assistance of high-quality personnel, management and system of medical service, to comprehensively upgrade the primary care and the quality of grass-roots general practitioners in remote mountainous areas.

Objective: To establish a rat model of preeclampsia (PE) in early pregnancy and to observe the changes in phenotype，pregnancy outcome and cognitive ability of offspring． Methods : The pregnant rats were randomly divided into model group and control group．Ultra-low dose lipopolysaccharide (LPS) (0. 5 μg / kg) and an equal volume of normal saline were injected into the tail vein of pregnant rats on the fifth day of pregnancy．The levels of blood pressure ，12-hour urinary protein ，peripheral blood coagulation factors and placental cytokines in the two groups were measured．Furthermore，placental pathology，pregnancy outcomes，and cognitive abilities of offspring were observed. Results: Blood pressure and urinary protein levels of model group were significantly higher than those of control group levels．Compared with the control group，the levels of platelet and antithrombin Ⅲ (AT Ⅲ) in the peripheral blood of pregnant rats in the model group were lower than those in the control group，while D-dimer was higher than that in the control group，the weight of the fetus and placenta in the model group decreased (P ＜0. 001) ，the expression levels of interleukin ( IL) -6，tumor necrosis factor α ( TNF-α) and interferon gamma (INF-γ) in peripheral blood increased，while the expression level of transforming growth factor β1 (TGF-β1) decreased(P＜0. 001) ．The water maze test showed that the latency of the offspring of the model group to the plat- form was longer than that of the control group (P＜0. 05) ，while the frequency of crossing the platform quadrant and the time of staying in the platform quadrant of the model group were lower than those of the control group (P < 0. 05 ) ．HE and PAS staining showed that there were infiltration of inflammatory cells in the basal layer of placenta， obvious decrease of blood vessels in labyrinthine area，slight edema of renal interstitium and degeneration of local renal tubular epithelial cells in the model group，while there were no above pathological changes in placenta and kidney in the control group． Conclusion A single injection of LPS in early pregnancy can successfully induce PE- related symptoms and adverse pregnancy outcomes such as fetal growth restriction and lead to the decline of cogni- tive ability of offspring.

Objective:To evaluate the feasibility and safety of carbon ion radiotherapy (CIRT) in the treatment of muscle-invasive bladder cancer in phase Ⅰ/Ⅱ clinical trials.Methods:Clinical stage T 2-3 patients with muscle-invasive bladder cancer (without distant metastasis) were studied. A three-fraction treatment was applied, including the local irradiation with the dose from 12 Gy to 24 Gy and 11 fractions of whole-bladder irradiation with a dose of 44 Gy. The carbon ion irradiation dose is determined with relative biological effectiveness (RBE) of 3.0. The total dose for bladder tumor was 56-68 Gy in 14 fractions. The primary endpoints included tumor treatment-related side effects, dose-limiting toxicity (DLT) responses, and local control (LC) rate, and the secondary endpoints included progression-free survival (PFS). Results:Nine patients received CIRT of various doses in the clinical trials, with the dose gradually increasing to 68 Gy. The patients did not suffer from DLT response, acute adverse effects of radiation therapy of grade ≥3, and late radiation adverse reactions during follow-up. When the dose to the tumor reached 68 Gy, there were 2 cases of grade 2 acute urogenital tract reaction and 1 case of acute lower gastrointestinal tract symptom. For the group with a dose above 62 Gy, three cases of grade 1 late radiation bladder reaction were observed and their symptoms included urinary frequency and microscopic hematuria. At the end of treatment, hematuria disappeared, dysuria was relieved, and urine red blood cell value significantly decreased for all the patients. Three months and six months after treatment, the LC rates were 100% and 88.9%, respectively, and the objective response rates were both 88.9%. One patient developed local recurrence and was treated with salvage surgery six months after treatment.Conclusions:The preliminary efficacy observation of CIRT in the treatment of muscle-invasive bladder cancer showed significant short-term efficacy, obvious symptom relief, and good tolerability for patients, without DLT. Therefore, CIRT is safe and feasible.

Objective To induce a novel temperate bacteriophage from staphylococcus haemolyticus strain SA98,observe the morphology and size,complete the whole genome sequencing,analyse the structure of genome and evolutionary relationship.Methods The mitomycin C was used to induce the temperate phage from staphylococcushaemolyticus strain SA98,the induced phage was observed by transmission electron microscopy after be concentrated and purified.The genome DNA was extracted and high through sequenced.The feature of whole genome and evolutionary relationship was analyzed.Results A temperate phage IME-SA4 was successfully induced from staphylococcus haemolyticus strain SA98.Transmission electron microscopy analysis indicated that IME-SA4 had an isometric head and a non-contractile long tail.The whole genome of IME-SA4 was long as 41 843 bp,and the whole genome blast result indicated IME-SA4 shared only 13％ homology with most related strain phiRS7.Conclusions A novel staphylococcus haemolyticus temperate phage with low homology with other staphylococcusphages was successfully induced from staphylococcus haemolyticus strain SA98.The research of its morphology,whole genome sequencing and comparative genome analysis make the foundation for further study of staphylococcus phages' properties and practical application.

Objective To evaluate the effect of recombinant human tumor necrosis factor receptor type Ⅱ:IgG Fc fusion protein (rhTNFR:Fc,trade name Etanercept) combined with methotrexate on levels of interleukin-17A (IL-17A) and tumor necrosis factor-α (TNF-α) in the serum and mononuclear cells of patients with moderate to severe plaque psoriasis.Methods A total of 30 patients with moderate to severe plaque psoriasis were enrolled from Department of Dermatology of Tenth People's Hospital of Tongji University between August 2014 and February 2016,and then were randomly and equally divided into Etanercept group and Etanercept + methotrexate group.The treatment lasted 24 weeks.Fifteen healthy blood donors served as healthy control group.Enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR were performed to measure the serum levels and mRNA expression of IL-17A and TNF-α,respectively,in the patients of the above two groups before and after the treatment.Results Before the treatment,the serum levels of IL-17A and TNF-ct,as well as the mRNA expression of IL-17A and TNF-α in peripheral blood mononuclear cells (PBMCs),were all significantly higher in all the patients than in the healthy controls (all P ＜ 0.05).After the treatment,compared with the Etanercept group,the Etanercept + methotrexate group showed significantly lower serum levels of IL-17A (142.67 ± 14.82 vs.163.54 ± 23.18,P ＜ 0.05) and TNF-α (70.07 ± 25.02 vs.91.98 ± 14.62,P ＜ 0.05),as well as lower mRNA expression of IL-17A (1.12 ± 0.33 vs.1.56 ± 0.77,P ＜ 0.05) and TNF-α in PBMCs (2.50 ± 1.04 vs.3.61 ± 2.14,P ＜ 0.05).Conclusion Etanercept combined with methotrexate is superior to Etanercept alone in the treatment of psoriasis,and can reduce treatment duration and improve therapeutic effect,likely by down-regulating the expression of IL-17A and TNF-α.

Hyperuricemia is a risk factor for various diseases, but knowledge on acute hyperuricemia is still not sufficient. The present study was aimed to investigate the effect of acute hyperuricemia on red blood cells from hemorheological point of view, and to provide the reference for clinical treatment. The rats were gavaged with 500 mg/kg hypoxanthine and intraperitoneally injected with 100 mg/kg oxonate to induce the model of acute hyperuricemia. The same volume of blood samples were drawn within time period of 0, 1, 2, 3 and 6 h, respectively, from the inner canthus of rats to measure the serum uric acid, hemorheological parameters and the malondialdehyde level. It was found that in each period of 1, 2 and 3 h, the rats had significantly higher levels of uric acid. The integrated deformation index and relax index were increased. The hemolysis rate was significantly reduced. The plasma malondialdehyde level was obviously decreased at the end of 2 h. The results suggested that short-term elevated uric acid could improve the hemorheological parameters and the lipid oxidative level in red blood cells.
Animals ; Erythrocytes ; Hemorheology ; Hyperuricemia ; blood ; Malondialdehyde ; blood ; Rats ; Rats, Sprague-Dawley ; Uric Acid ; blood

Autophagy is an evolutionarily conserved cellular process which degrades intracellular contents. The Atg17-Atg31-Atg29 complex plays a key role in autophagy induction by various stimuli. In yeast, autophagy occurs with autophagosome formation at a special site near the vacuole named the pre-autophagosomal structure (PAS). The Atg17-Atg31-Atg29 complex forms a scaffold for PAS organization, and recruits other autophagy-related (Atg) proteins to the PAS. Here, we show that Atg31 is a phosphorylated protein. The phosphorylation sites on Atg31 were identified by mass spectrometry. Analysis of mutants in which the phosphorylated amino acids were replaced by alanine, either individually or in various combinations, identified S174 as the functional phosphorylation site. An S174A mutant showed a similar degree of autophagy impairment as an Atg31 deletion mutant. S174 phosphorylation is required for autophagy induced by various autophagy stimuli such as nitrogen starvation and rapamycin treatment. Mass spectrometry analysis showed that S174 is phosphorylated constitutively, and expression of a phosphorylation-mimic mutant (S174D) in the Atg31 deletion strain restores autophagy. In the S174A mutant, Atg9-positive vesicles accumulate at the PAS. Thus, S174 phosphorylation is required for formation of autophagosomes, possibly by facilitating the recycling of Atg9 from the PAS. Our data demonstrate the role of phosphorylation of Atg31 in autophagy.
Alanine ; chemistry ; metabolism ; Amino Acid Motifs ; Aspartic Acid ; chemistry ; metabolism ; Autophagy ; genetics ; Autophagy-Related Proteins ; Carrier Proteins ; chemistry ; metabolism ; Gene Expression Regulation, Fungal ; Membrane Proteins ; chemistry ; metabolism ; Models, Molecular ; Molecular Sequence Data ; Nitrogen ; deficiency ; Phagosomes ; chemistry ; drug effects ; metabolism ; Phosphorylation ; Protein Transport ; Saccharomyces cerevisiae ; drug effects ; genetics ; metabolism ; Saccharomyces cerevisiae Proteins ; chemistry ; genetics ; metabolism ; Serine ; chemistry ; metabolism ; Signal Transduction ; Sirolimus ; pharmacology