BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.
Humans ; HEK293 Cells ; Sincalide ; China ; Amanita ; Death, Sudden

Intestinal Peyer's patches （PPs） are local immune tissues of the intestine， which are considered to be the main induction site of the intestinal mucosal immune response， and closely related to immune-related refractory enteropathies， such as ulcerative colitis and Crohn's disease. In recent years， more and more scholars have tried to find a new breakthrough for treating refractory enteropathies with a limited efficacy of clinical interventions through in-depth study of the relationship between PPs and enteropathy. Traditional Chinese medicine （TCM） polysaccharides are considered to be a key component for immune regulation with TCM. Modern studies show that TCM polysaccharides have a significant positive intervention effect on the structure and function of PPs， with good development prospects. Based on this， this paper focuses on PPs and intestinal-related diseases， and systematically introduces the physiological structure of PPs and their drug delivery mechanism， and summarizes the interactions of PPs with effect on immune-related enteropathies， analyze of current studies and prospects of effect of TCM polysaccharides in intervening intestinal disease and its dysfunction by regulating PPs， with the aim to provide new strategies for basic studies and clinical treatment of immune-related refractory enteropathies from the perspective of PPs， and new ideas for basic studies and clinical studies on effect of TCM polysaccharides in intervening enteropathies.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective:To investigate the analgesic time-effect characteristics and changes in concentrations of rabbit's hypothalamic 5-hydroxytryptamine (5-HT) and noradrenaline (NE) caused by buccal acupuncture in the rheumatoid arthritis (RA) rabbits,and to reveal the analgesic central mechanism of buccal acupuncture,thereby providing a theoretical basis for the treatment of pain by buccal acupuncture.Methods:Forty rabbits were randomly divided into a normal group,a model group,a body acupuncture group,and a buccal acupuncture group,with 10 rabbits in each group.No model was established in the normal group,while equal dose of normal saline was injected at the matched site and time point;rabbits in other groups were subjected to the establishment of RA models using egg protein.From the 27th day of the experiment,rabbits in each group received the designated intervention.Rabbits in the normal group and the model group were fixed for 30 min every day using the same method as those in the other groups.In the acupuncture group,Dubi (ST 35) and Zusanli (ST 36) on bilateral hind limbs were selected.Perpendicular needling (using the needles with 0.25 mm in diameter and 25 mm in length) was performed with twirling manipulation for 15 s at intervals of 5 min.The needles were retained for 30 min and acupuncture was performed once a day.In the buccal acupuncture group,the knee point in the buccal acupuncture and needles with a diameter of 0.25 mm and a length of 15 mm were selected.Oblique needling was performed with twirling manipulation for 15 s at intervals of 5 min.The needles were retained for 30 min and acupuncture was performed once a day.The thermal pain thresholds at the 0,5,15,30,60,120 and 240 min after the 1st and 10th acupuncture therapy were measured with a PL-200 thermal-inducing pain meter.After the 10th acupuncture therapy,rabbit's hypothalamus was removed,and the 5-HT and NE concentrations in the hypothalamus at the peak point of the acupuncture pain threshold curve were determined by high performance liquid chromatography (HPLC).Results:The analgesic effect was obvious at 5 min after buccal acupuncture started,peaked at 30 min,and decreased to the lowest value at 240 min.Rabbits in the body acupuncture group began to show significant analgesic effect at 15 min,which was peaked at 30 min,and began to decline at 60 min.The pain threshold at 240 min was still higher than that at 0 min.Compared with the model group,the concentrations of hypothalamic 5-HT in the buccal acupuncture group and the body acupuncture group was significantly increased,and the between-group differences were statistically significant (both P＜0.05).The NE/5-HT ratios in hypothalamus in the buccal acupuncture group and the body acupuncture group were significantly lower than the ratio in the model group,and the differences were statistically significant (both P＜0.05);difference in the decrease was statistically significant between the buccal acupuncture group and the body acupuncture group (P＜0.05).Conclusion:The analgesic effect of buccal acupuncture shows an obvious time-dependent curve.It is characterized by rapid onset of pain relief,rapid increase and decline in pain threshold.5-HT and NE levels in rabbit's hypothalamus can be affected by buccal acupuncture,with increased 5-HT concentration and reduced NE/5-HT ratio.

Objective To discuss the different clinical features and prognosis of single cerebral venous thrombosis (CVT) and multiple CVT. Methods The site and the number of vein and thrombosed sinuses of 136 patients with CVT were summarized. The patients were divided into 2 groups according to the numbers of thrombosed sinuses. The clinical features and outcome of the patients with single CVT were analyzed in comparison with those with multiple CVT by univariate analysis. Results In 44 patients (32.4%), only 1 cerebral sinus was involved. In 92 patients (67.6%), 2 or more cerebral veins and sinuses were involved (2 sinuses in 45, 3 sinuses in 35, 4 sinuses in 9, 5 sinuses in 3). The lateral sinus and the sigmoid sinus were the most frequent thrombosed sinuses which were found in 86.8% of patients; the followings were superior sagittal sinus (58.1%), straight sinus (18.4%) , deep venous system (7.4%), and cortical veins (2.9%). Mean ages were significantly older but the short-term prognosis was better in the group of patients with single CVT in comparison with those in the group of patients with multiple CVT. The patients with multiple CVT also presented more serious intracranial hypertension, more frequent parenchymal lesions and systematic thrombotic events than those with single CVT (P＜0.05). Conclusion In most CVT patients, 2 or more veins and sinuses are involved and thromboses most commonly implicate the lateral sinus and the superior sagittal sinus. Patients with multiple CVT usually present higher intracranial pressure, more serious clinical course, worse outcome and higher incidence of systematic venous thrombotic events in comparison with patients with single CVT. And the multiple sinus thrombosis is more likely to cause venous infarctions and intracranial hemorrhage than the single one.

OBJECTIVETo understand the prevalence of sleep disordered breathing (SDB) in elderly patients with coronary artery disease (CAD) and explore the relations between SDB and CAD.

METHODSSixty-two elderly patients with and 18 without CAD identified by coronary angiography underwent examinations by polysomnography (PSG). Left ventricular ejection fraction (LVEF) was measured by 99Tc equilibrium radionuclide angiography.

RESULTSIn the 62 elderly patients with CAD, 53.2% had SDB, a rate significantly higher that (22.2%) in the 18 non-CAD patients. The CAD patients with SDB had higher respiratory disturbance index (RDI) and body mass index (BMI) and lower arterial saturation of oxygen (SaO2) during sleep, with longer duration of low SPO2 (less that 90%). The incidence of hypertension was higher in CAD patients with SDB than in those without SDB. No significant correlation was found between the severity of coronary artery disease and RDI (r=-0.16, P>0.05).

CONCLUSIONThe elderly patients with CAD have higher incidence of SDB, and appropriate interventions should be administered in those with severe SDB.

Aged ; Aged, 80 and over ; China ; epidemiology ; Coronary Angiography ; Coronary Artery Disease ; complications ; diagnostic imaging ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Polysomnography ; Prevalence ; Sleep Apnea Syndromes ; complications ; epidemiology ; physiopathology

OBJECTIVESTo discuss the methods and outcome of shorting proximal femoral and total hip arthroplasty for Crowe IV dysplastic hip of adults.

METHODSFrom July 2000 to February 2006, 13 cases of osteoarthritis secondary to severe development dysplastic hip were treated by total hip replacement and the shorting proximal femoral.

RESULTSThe duration of follow-up ranged from 4 months to 55 months. The average score increased from 36.9 to 84.1 points after the surgery according to Harris. All the patients could walk independently. Their paces were improved obviously and the function of their hips was satisfactory.

CONCLUSIONSThe treatment by total hip arthroplasty and the shorting of posterior femoral is effective and efficient for osteoarthritis secondary to Crowe IV development dysplastic hip in adults. The long-term followup is necessary for further study.

Adult ; Aged ; Arthroplasty, Replacement, Hip ; methods ; Female ; Femur ; surgery ; Follow-Up Studies ; Hip Dislocation ; etiology ; surgery ; Humans ; Male ; Middle Aged ; Osteotomy ; methods ; Retrospective Studies ; Treatment Outcome

BACKGROUNDLarge animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin (STZ)-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta) and interleukin-6 (IL-6).

METHODSTwenty-two male Chinese Guizhou minipigs (age, 4 to 6 months; weight, 20 kg to 30 kg) were divided into STZ-induced diabetic group (n = 12) and control group (n = 10). STZ (125 mg/kg) was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test (OGTT) was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparagine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet beta cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-alpha level in tissue conditioned medium by Western blot. TNF-alpha, IL-1beta and IL-6 mRNA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction (RT-PCR).

RESULTSSignificant elevation in serum glucose levels was observed one month and six months after STZ induction (P < 0.001) and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet beta cells, while in pancreas of diabetic minipigs islet beta cells almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Western blot demonstrated dramatically increased TNF-alpha level in aotic intima conditioned medium, and significant elevation of TNF-alpha, IL-1beta and IL-6 mRNA levels was revealed by RT-PCR.

CONCLUSIONSThe present study has established Chinese Guizhou minipig models with STZ-induced diabetes. Inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) significantly elevated in aortic intima of diabetic minipigs.

Animals ; Aorta ; chemistry ; Diabetes Mellitus, Experimental ; immunology ; pathology ; Glucose Tolerance Test ; Immunohistochemistry ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Male ; Pancreas ; pathology ; Streptozocin ; Swine ; Swine, Miniature ; Tumor Necrosis Factor-alpha ; blood

To enhance the DNA immunogencity of PRRSV ORF5 gene, CpG sequence and the universal helper T cell antigen epitope (PADRE) sequence were inserted between the decoy epitope and the neutralizing epitope. At the same time, site-mutations were introduced at N33 and N51 to diminish the coverage effect to epitope B from the polysaccharides. Subsequently, the modified ORF5 gene (MORF5) and PRRSV ORF6 gene were cloned into the eukaryotic expression vector pcDNA3.0 under the control of two CMV promoters, respectively. With indirect immunofluorescence assay and Western-blot the expression in vitro of the two genes was confirmed, then six-week-old Balb/C mouse were immunized with the modified expression plasmid pcDNA-M5A-6A. The non-modified expression plasmid pcDNA-5A-6A, the blank eukaryotic expression plasmid pcDNA3.0, living attenuated vaccine and inactivated vaccine were used as controls. The PRRSV specific neutralizing antibodies and the T cell proliferation response were elevated with virus neutralization assay and MTf method. Results indicate that the modified plasmid pcDNA-M5A-6A can elicit not only higher titer of neutralizing antibodies in a rapid time, but also more vigorous T cell proliferation response compared with the non-modified plasmid pcDNA-5A-6A and commercial vaccines, indicating that DNA vaccine pcDNA-M5A-6A maybe a promising candidate for PRRS prevention.
Animals ; Antibodies, Neutralizing ; immunology ; Antibodies, Viral ; blood ; immunology ; Binding Sites ; genetics ; Blotting, Western ; CHO Cells ; Cell Proliferation ; Cricetinae ; Cricetulus ; Female ; Glycosylation ; Mice ; Mice, Inbred BALB C ; Mutation ; Open Reading Frames ; genetics ; Porcine Reproductive and Respiratory Syndrome ; immunology ; prevention & control ; Porcine respiratory and reproductive syndrome virus ; genetics ; immunology ; metabolism ; Swine ; virology ; T-Lymphocytes ; cytology ; immunology ; metabolism ; Vaccines, DNA ; administration & dosage ; immunology ; Viral Proteins ; genetics ; immunology ; metabolism ; Viral Vaccines ; administration & dosage ; immunology