Objective To investigate the association among daytime sleepiness,serum tumor necrosis factor(TNF)-α levels and microarousal in patients with obstructive sleep apnea hypopnea syndrome (OSAHS).Methods Forty male patients with OSAHS conformed by apnea hypopnea index(AHI)during sleep monitoring of polysomnography were selected as OSAHS group,15 healthy subjects were selected as control group.The level of serum TNF-α was measured by ELISA.The Epworth sleepiness(EP)scale was used in two groups.Results The level of serum TNF-α in OSAHS group[(18.42±6.23)ng/L]was significantly higher than that in control group[(9.75±3.12)ng/L],P＜0.01.The EP scale and micmarousal index were signifieand yhigher in OSAHS group than those in control group[(16.9±4.7)acores vs(4.5±2.3)dcores,(33.6±16.9)times/h vs(11.3±7.3)times/h,P＜0.01].The EP scale in OSAHS group was positively correlated with the levels of serum TNF-α(r=0.461,P＜0.01),AHI(r=0.443,P＜0.01)and microarousal index(r=0.751,P＜0.01)respectively.The levels of serum'INF-α in patients with OSAHS were also positively correlated with microarousal index(r=0.373,P＜0.01).Conclusions The levels of serum TNF-α and mieroarousal index are increased in patients with 0SAHS.The microarousal related to OSAHS plays an important role on the daytime sleepiness,the unusual levels of serum TNF-α maybe lead to interferen of sleepiness.

ObjectiveTo observe the effect of 99Tc-methylene diphosphate (99Tc-MDP, Yunke) combined with rehabilitation on ankylosing spondylitis (AS).Methods118 AS patients were randomly divided into the treatment group (n=58) and control group (n=60). The treatment group was treated with meloxicam, sulfasalazine and vein injecting Yunke combined rehabilitation. The control group was treated only with meloxicam and sulfasalazine. The changes of both clinical and experimental indexes of two groups before and after treatment were analyzed.ResultsAfter two therapeutic courses, a much better result was obtained in the treatment group compared with the control group at the respects of releasing arthralgia, shortening morning stiffness, improving range of spinal motion, and decreasing the levels of ESR, CRP, PLT and IgM, ect (P<0.05～0.01) without obvious side effects.ConclusionThe effect of Yunke combined with rehabilitation on AS is evident.

Objective: To investigate the inhibitory effects and mechanism of Triticum aestivum (TA) on anaphylaxis in ovalbumin (OVA)-sensitized mice. Methods: Twenty-five female BALB/c mice were randomly divided into five groups (n=5), including control group, OVA group, 100 mg/kg TA group, 200 mg/kg TA group and DEX (dexamethasone) group. OVA (20 μg) and aluminum hydroxide (1 mg) were dissolved in 100 μl of PBS solution and injected into the abdominal cavity of each experimental mouse, while the mice in the control group were injected with 100 μl of 0.9% normal saline. All mice were given drinking water. The above processes were repeated two weeks later, and different concentrations of experimental drugs were diluted in 1% CMC (carboxymethyl cellulose) solution to feed mice. Allergic symptoms and behaviors of each mouse were scored in the process of feeding. On the 12th day after first sensitization, mice in the control and experimental groups were subcutaneously injected in the auricle with 20 μl of 0.9% saline solution and OVA, respectively. The thickness of each mouse′s auricle was measured 6 and 24 hours later. Histopathologic changes in auricle tissues were observed by hematoxylin-eosin(HE) staining 24 hours later. The mice were euthanized by cervical dislocation in the 6th week after first sensitization. Abdominal aorta serum samples were collected and tested for specific inflammatory cytokines (IgE, IgG1, TNF-α, IL-4) and anti-OVA antibodies (IgE, IgG1) by ELISA. ELISA and RT-PCR were used to detect the expression of IFN-γ, IL-4, IL-5, IL-12 and IL-13 after spleen lymphocytes were stimulated with different concentrations of drugs. Results: Both the score of allergic symptoms and behavior and the thickness of the auricle of the OVA group were the highest among all groups (P<0.05). A TA dose-dependent decrease was found in both of the two parameters, which was confirmed by histopathological analysis. ELISA results showed that the plasma levels of IgE, IgG1, IL-4 and TNF-α in the experimental groups were significantly higher than those in the control group, but all of them were decreased in a TA dose-dependent manner. TA at the high concentration of 200 mg/kg was similar to DEX in inhibiting the expression of IgE and TNF-α. RT-PCR results showed that Th1 cytokines (IFN-y and IL-12) in the experimental groups increased significantly as compared with those in the control group (P<0.05). Expression of IFN-y and IL-12 was not significantly affected by TA at various concentrations, but markedly inhibited by DEX. The levels of Th2 cytokines (IL-4, IL-5 and IL-13) in the experiment groups were significantly higher than those in the control group (P<0.05). Compared with the OVA group, the levels of IL-4, IL-5 and IL-13 were significantly reduced in TA groups, especially in the TA 100 μg/ml group in which the expression of the three cytokines was decreased by about 60%, 18% and 20%, respectively. Conclusion TA helps to maintain immune balance by selectively inhibiting the expression of Th2 cytokines (IL-4, IL-5, IL-13), IgE and IgG and not influencing Th1 cytokines (IFN-γ and IL-12). It has an anti-allergic effect as it effectively suppresses allergic responses. This research provides both theoretical and experimental basis for further development of novel anti-anaphylactic treatment with TA.

Objective To establish a nomogram prediction model of hyperuricemia(HUA)onset risk in overweight and obese children and adolescents in order to provide reference for the prevention and treatment of HUA in this population.Methods The clinical data of 1 410 overweight and obese children and adolescents aged 6-17 years old visiting in this hospital from September 2021 to August 2022 were retrospectively analyzed.A total of 987 overweight and obese children and adolescents were randomly extracted according to a ratio of 7:3 to establish the model,and the remaining 423 cases were validated internally.Referring to the definition of high uric acid in"Zhu-futang Practical Pediatrics",the subjects were divided into high uric acid group and non-high uric acid group.The logis-tic regression analysis was used to analyze the influencing factors of HUA in overweight and obese children and adoles-cents.The nomogram model was constructed by using the R language.The area under the receiver operating character-istic(ROC)curve(AUC),decision analysis curve(DIC),clinical impact curve(CIC)and C-index were used to evalu-ate the predictive ability of the model,and the Bootstrap repeated sampling method(taking samples for 1000 times)was used for internal validation of the model.Results The results of multivariate analysis showed that the age(OR=2.324,95％CI:1.155-4.672,P=0.018),gender(OR=0.456,95％CI:0.256-0.810,P=0.007),triglycerides(OR=3.775,95％CI:2.321-6.138,P＜0.001),blood calcium(OR=26.986,95％CI:3.186-228.589,P=0.003)and blood creatinine(OR=1.047,95％CI:1.026-1.070,P＜0.001)were the influen-cing factors of HUA in overweight and obese children and adolescents.AUC of the ROC curve of the model was 0.840,the sensitivity was 0.786,the specificity was 0.762,the Youden index was 0.548,and the C-index was 0.840.The risk probability of DC A was 0.1-0.8,the net benefit rate of both models was＞0,AUC of ROC curve in the internal verification was 0.871.Conclusion The constructed nomogram in this study has a good predictive efficiency for the onset risk of HUA in overweight and obese children and adolescents,and may provide reference for the early diagnosis and treatment of this population.

Objective To investigate the mechanism of Qinggan-Huoxue recipe in the treatment of alcoholic liver disease by observing its function on alcoholic liver disease rat fibroblast growth factor -21 (FGF21). Methods The rats were randomly divided into the blank group (n=10), the carbon tetrachloride group (n=10), the model group (n=11), the Qinggan-Huoxue recipe group (n=10), the Qinggan recipe group (n=9) and the Huoxue recipe group (n=10). Except for the blank group and the carbon tetrachloride group, the other rats were given 10 ml/kg alcohol, corn oil and pyrazole mixture (4.5 ml: 2 ml: 25 mg), once a day, 0.3 ml/kg carbon tetrachloride olive oil solution (carbon tetrachloride: olive oil =1: 3) intraperitoneally, and twice a week for 12 weeks to prepare the alcoholic liver disease model. In the ninth week, the Qinggan-Huoxue recipe group was treated with 4.75 g/kg of Qinggan-Huoxue recipe, the Qinggan recipe group was treated with 1.5 g/kg of Qinggan recipe, and the Huoxue recipe group was treated with 3.25 g/kg of Huoxue recipe, once a day, and 28 d for continuous administration. The pathological changes of liver tissue were observed by HE staining and Masson staining. The serum levels of AST and ALT were detected in rats. The changes of FGF21 protein and mRNA expression were detected by immunohistochemistry, Western blotting and fluorescence quantitative PCR. Results Compared with the model group, the liver weight and liver body ratio in the Qinggan recipe group, Qinggan-Huoxue recipe group and Huoxue recipe group were significantly lower (P<0.01). Compared with the model group, the serum ALT (41.95 ± 26.78 U/L, 46.63 ± 21.00 U/L, 37.57 ± 27.85 U/L vs. 138.34 ± 43.35 U/L), AST (102.74 ± 23.55 U/L, 111.50 ± 21.26 U/L, 83.72 ± 37.57 U/L vs. 257.41 ± 162.31 U/L) in the Qinggan recipe group, Qinggan-Huoxue recipe group and Huoxue recipe group significantly decreased (P<0.01 or P<0.05). Compared with the model group, the expression of FGF21 protein (1.19 ± 0.07, 1.24 ± 0.12 vs. 0.92 ± 0.04) in Qinggan recipe group and Qinggan-Huoxue recipe group significantly increased (P<0.05), and the expression of FGF21 mRNA (1.25 ± 0.08 vs. 0.95 ± 0.05) in Qinggan-Huoxue recipe group significantly increased (P<0.05). Conclusions FGF21 plays an important role in the alcoholic liver disease. During the process of liver injury, FGF21 increases continuously. Qinggan-Huoxue recipe can improve the content of FGF21 in the treatment of alcoholic liver disease.

The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.

BACKGROUNDGiant cell interstitial pneumonia (GIP) was a rare form of pneumoconiosis, associated with exposure to hard metals, which had been reported mostly as isolated case reports. We described eight cases of GIP diagnosed in our hospital during the past seven years, with particular reference to new findings.

METHODSEight patients with GIP confirmed by biopsy in the Nanjing Drum Tower Hospital affiliated to Medical School of Nanjing University from 2005 to 2011 were retrospectively analyzed. For each patient, the occupy histories and medical records were thoroughly reviewed and clinic data were extracted. Two radiologists, without knowledge of any of the clinical and functional findings, independently reviewed the HRCT scans of all patients. Follow-up data were collected.

RESULTSAmong the eight patients, seven had a history of exposure to hard metal dusts, one denied an exposure history. The most common manifestations were cough and dyspnea. One patient initiated with pneumothorax and another pleural effusion, both of which were uncommon to GIP. The main pathologic appearances were the presence of macrophages and multinucleated giant cells in the alveolar space. The clinical symptoms and radiographic abnormalities were obviously improved after cessation of exposure and receiving corticosteroid treatments, recurrences were observed in two patients when they resumed work. In spite of exposure cessation and corticosteroid treatment, one patient developed pulmonary fibrosis at seven years follow-up.

CONCLUSIONSAwareness of the patients' occupational history often provided clues to the diagnosis of GIP. Histopathologic examinations were necessary to establish the right diagnosis. Exposure cessation was of benefit to most patients; however, pulmonary fibrosis was possible in spite of exposure cessation and corticosteroid treatment. Better ways should be found out to improve the outcome and quality of life.

Adult ; Alloys ; toxicity ; Cobalt ; toxicity ; Female ; Humans ; Lung ; pathology ; Lung Diseases, Interstitial ; diagnosis ; etiology ; Male ; Middle Aged ; Pulmonary Fibrosis ; diagnosis ; etiology ; Retrospective Studies ; Tungsten ; toxicity ; Young Adult

Objective    To investigate the diagnostic value and safety of electromagnetic navigation bronchoscopy combined with radial endobronchial ultrasound in peripheral pulmonary nodules. Methods    The clinical imaging, surgical and pathological data of 60 patients with 76 peripheral pulmonary nodules who underwent electromagnetic navigation bronchoscopy combined with radial endobronchial ultrasound guided biopsy in the Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School from June 2020 to June 2021 were retrospectively analyzed. The diagnosis rate and complications were analyzed and summarized. The 76 pulmonary nodules were divided into a small pulmonary nodules group (10 nodules, diameter≤1 cm) and a pulmonary nodules group (1 cm