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Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.
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Background: Abnormal glucose metabolism is one of the malignant characteristics of tumors. LncRNA plays an important role in the process of aerobic glycolysis of tumors. Aims: To investigate the expression of LncRNA MEG3 in gastric cancer and its correlation with glycolysis. Methods: RT-qPCR was used to detect the mRNA expression of MEG3 in gastric cancer and paracancerous tissue. Immunohistochemical EnVision method was used to detect the protein expressions of PKM2, LDHA, mTOR, HIF-1α in gastric cancer and paracancerous tissue. Relationship between expressions of above-mentioned indices and clinicopathological features of gastric cancer were analyzed. The correlation between MEG3 and glycolysis level of gastric cancer was analyzed by Spearman correlation analysis, and its possible mechanism was explored. Results: The expression of MEG3 in gastric cancer tissue was significantly lower than that in paracancerous tissue (P< 0.05), and was correlated with lymph node metastasis (P<0.05). The positivity rates of expression of PKM2, LDHA, mTOR and HIF-1α in gastric cancer tissue were significantly higher than those in paracancerous tissue, and were correlated with the depth of tumor invasion, lymph node metastasis and pTNM stage (P<0.05). Spearman correlation analysis showed that the expression of MEG3 was negatively correlated with the expressions of PKM2, LDHA, mTOR and HIF-1α (r=-0.346，r= -0.306，r=-0.389, r=-0.338; P<0.05). The expression of MEG3 in HIF-1α
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Objective To explore the diagnostic value of bronchofiberscopic washing cytology (BWC) and bronchoalveolar lavage fluid (BALF) ThinPrep cytology test (TCT) in the diagnosis of lung cancer.Methods Three hundred and eighty-five lung cancer patients who completed the BWC and BALF TCT were selected.The sensitivity was compared between the conventional smear and the two TCT methods.The sensitivity and accuracy of BWC and BALF TCT in the diagnosis of lung cancer were analyzed.Results The sensitivity of TCT was 76.1％ (293/385) in the diagnosis of lung cancer,and conventional smear was 54.8％ (211/385).The sensitivity of TCT was significantly higher than that of conventional smear (P ＜ 0.05).In the diagnosis of central lung cancer,the sensitivity of BWC TCT and BALF TCT was 74.4％ (131/176) and 70.5％ (124/176),and there was no statistical difference (P ＞ 0.05).In the diagnosis of peripheral lung cancer,the sensitivity of BALF TCT and BWC TCT was 83.3％ (174/209) and 44.0％ (92/209),and there was statistical difference (P ＜ 0.05).In BWC TCT,the accuracy of TCT and histology in squamous cancer was 92.7％ (127/137),in adenocarcinoma was 92.6％ (151/163),in small cell cancer was 96.8％ (61/63),and total accuracy was 91.9％ (354/385).In BALF TCT,the accuracy of TCT and histology in squamous cancer was 92.0％ (126/137),in adenocarcinoma was 94.5％ (154/163),and in small cancer was 98.4％ (62/63),and total accuracy was 92.7％ (357/385).Conclusions TCT has more diagnostic value in lung cancer.BWC and BALF TCT show different sensitivity in the diagnosis of lung cancer of different kinds.BWC TCT combination with BALF TCT is helpful to improve the diagnosis of lung cancer.
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Purpose To study the clinicopathological features, immunophenotype and differential diagnosis of proximal epithelioid sarcoma (PES).Methods The clinical, radiological and pathological features were reviewed in 6 cases of PES.Results The patients consisted of five males and one female with ages ranging from 32 to 74 years (mean 56 years). Clinically, the tumor mass were progressively-growing solitary nodules with the fuctional disorder and pain. The sites of the tumor involvement were buttock (1 case), thigh (2 cases), iliac spine (1 case), lumbar spine (1 case) and anterior sacrum (1 case). Histologically, the tumors were mainly consisted of epithelioid cells with round or oval nuclei, prominent nucleoli and eosinophilic cytoplasm, some tumor cells appeared rhabdoid features. Immunohistochemically, the tumor cells were positive for vimentin (6/6), CK (5/6), EMA (6/6),β-catenin (6/6), CD99 (5/6), and CD34 (4/6), but negative for S-100 protein, HMB 45, CD 117 and CD 31.Conclusion PES is a distinctive moderate grade malignant tumor with prominent epithelioid and rhabdoid cells appearance.The differential diagnoses include the tumors that have similar cellular appearance with PES, and immunohistochemical staining is useful for diagnosis and differential diagnosis.
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Objective To compare the effect of different flow rate of oxygen inhalation on relieving scapuledynia after laparoscopic cholecystectomy(LC) with carbon dioxide pneumoperitoneum. Methods 100 patients adopted LC were divided into the 2 L/min group (n=50), the 4 Ldmin group (n=50), both re-ceived oxygen inhalation 6 hours after LC. The incidence and degree of scapulodynia and the blood- gas analysis were analyzed. Results The incidence of scapulodynia after LC in the 4 L/min group was signifi-cantly lower than that of 2 L/min group. PaCO2,PaO2 and pH in the 4 L/min group were different from those of the 2 L/min group. Conclusions Increasing flow rate of oxygen inhalation can relieve incidence and degree of scapulodynia after laparoscopic cholecystectomy.
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OBJECTIVE: To study the mechanism of herbal application along meridians for treatment and prevention of asthma by using serum pharmacological test to observe the effects of serum containing herbs against the constriction of tracheal spiral strips induced by acetylcholine chloride (Ach). METHODS: Guinea pigs were randomly divided into normal control group, normal saline (NS) application group, aminophylline application group, aminophylline injection group, 1-day herb application group, 7-day herb application group and 14-day herb application group. Asthma was induced by Hutson's method in guinea pigs except the normal control group. Guinea pigs in herb application groups were treated by external application of a compound herbal medicine 60 min once every day. Guinea pigs in NS application group were treated by external application of NS. Guinea pigs in the two aminophylline-treated groups were treated by external application and intraperitoneal injection of aminophylline at a dose of 400 mg/kg, respectively. The guinea pigs were killed and the sera were obtained after 1-day, 7-day and 14-day treatment in the three herb application groups, 7-day treatment in the NS application group, the aminophylline application and injection groups, respectively. Serum pharmacological method was used to do the experiment, the effects of different sera on the constriction of tracheal strips were observed, and the constriction rates were calculated. RESULT: The serum containing herbs had an effect in reducing the constriction of tracheal spiral strips induced by Ach, and the effect was similar to that of the serum obtained from the aminophylline injection group. The constriction rate of the tracheal spiral strips was decreased when herbal application treatment was prolonged within a period of time, and it became stable when herbal application treatment was between 7-14 days. The constriction of tracheal spiral strips induced by Ach could be reduced remarkably when it was previously treated by serum containing herbs. CONCLUSION: The anti-acetylcholine function with a time-dependent effect is one of the mechanisms of herbal application treatment along meridians for asthma, and furthermore, herbal application treatment along meridians might be useful for preventing asthma.
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[Objective]To investigate the effect of salvianoli acid B and hyperoxic solution on experimental ischemia reperfusion injury of extremities.[Method]Twenty-four healthy New Zealand rabbits were divided into 4 groups randomly.Equivalent 0.9%Nacl(group A),hyperoxic solution(group B),salvianoli acid B(group C),salvianoli acid B and hyperoxic solution(group D) were injected through ear edge vein before ischemia.The femoral artery and vein were blocked and the model of ischemia reperfusion injury of extremities was set up.Before ischemia and after 4 hour's reperfusion,the blood samples were taken to measure the levels of blood malondialdehyde(MDA) and superoxide dismutase(SOD).The gastrocnemius muscles were observed by pathologic test.[Result]Serum enzymatic activity of MDA improved obviously.Salvianoli acid B and hyperoxic solution could prevent the improvement of it(P
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OBJECTIVE: To investigate the effects of Guizhi Decoction, Chaihu Guizhi Decoction, Xiaochaihu Decoction and camostat on rat spontaneous chronic pancreatitis and the pathological relationships between formulas and syndromes. METHODS: Fifty-seven male WBN/Kob rats at age of 4 weeks were divided into five groups: untreated group (n=18), Guizhi Decoction-treated group (n=9), Chaihu Guizhi Decoction-treated group (n=9), Xiaochaihu Decoction-treated group (n=9) and camostat-treated group (n=12). The rats in each group were fed with corresponding drugs for 12 weeks. The pancreatic wet weight and histopathological changes of pancreatic tissue were observed every four weeks. Meanwhile, the expression level of pancreatitis-associated protein (PAP) in pancreas was detected by RT-PCR technique and immunohistochemical method. RESULTS: In the untreated group, the histopathological changes in pancreas were observed in rats at 12-week age, while such changes were absent in the Guizhi Decoction-treated group. The histopathological changes in pancreas were quite remarkable in rats at 16-week age in both the Xiaochaihu Decoction-treated and the camostat-treated groups. The expression level of PAP mRNA was lower in the Guizhi Decoction-treated group than those in the other groups. The PAP expressions were absent in rats at 12-week age in the Guizhi Decoction-treated and the Chaihu Guizhi Decocion-treated groups. CONCLUSION: Guizhi Decoction, Chaihu Guizhi Decoction, Xiaochaihu Decoction and camostat are all beneficial to prevention and cure of chronic pancreatitis, and Guizhi Decoction is the most effective one. It is speculated that Taiyang exterior syndrome may be the pathogenesis of basic syndrome may be the pathogenesis of basic syndrome of spontaneous chronic pancreatitis, and the expression of PAP may be its pathological basis.
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To observe the curative effect and the hemodynamic change of cervical vertigo treated by acupuncture, 66 patients were randomly divided into two groups: group A in which acupoints Yuzhen (BL 9) and Fengchi (GB 20) were used and Group B in which Cervical Jiaji points (C4-6) were used. Before and after treatment, the symptom of the cervical vertigo and the grade variety of function and the change of Color Doppler Flow Imaging (CDFI) of vertebral artery were observed. After treatment, the grade in two groups increased, there was a remarkable difference between two groups(P ＜ 0.05); after treatment, the grade of vertigo degree increased, there was a remarkable difference between two groups(P ＜ 0.05); needling Yuzhen (BL 9) and Fengchi (GB 20) can remarkably improve the symptom of cervical vertigo and vertebral artery blood flow rate, and the curative effect was superior to needling Jiaji points.
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AIM: To evaluate the pulmonary function in patients with type 2 diabetes mellitus in order to identify whether the lung is a target organ of chronic pathologic changes in diabetes mellitus. METHODS: Pulmonary ventilation function and diffusion capacity were studied in 107 patients with type 2 diabetes mellitus and 61 healthy subjects matched for age and sex. Glycosylated hemoglobin (HbA1c), urine albumin excretion rate (AER), fundus examination and nerve conduction velocity were included as parameters of glycemic control and diabetic microangiopathies. RESULTS: Pulmonary ventilation function was similar in type 2 diabetic group and the control. Compared with the control, carbon monoxide diffusion capacity (DLCO) and DLCO corrected by alveolar volume (DLCO/VA) were significantly lower in type 2 diabetic group (P<0.05). DLCO and DLCO/VA were inversely correlated with microangiopathy score (r: -0.291, -0.324, respectively, P<0.01). Furthermore, DLCO/VA was negatively correlated with age and duration of diabetes mellitus (r: -0.269, -0.236, respectively, P<0.05). CONCLUSIONS: Pulmonary ventilation function is normal in patients with type 2 diabetes mellitus, but their diffusion capacity is impaired. It suggests that the lung may also be the target organ of the chronic pathologic changes of diabetes mellitus.