Establishment of a hyperuricemia rat model by stimulation of high temperature-humidity environment / 中华内分泌代谢杂志

Objective:To establish a hyperuricemia rat model through the high temperature-humidity treatment, and monitor its vital signs and biochemical indicator characteristics, as well as observe the changes of renal histomorphology and ultrastructure.Methods:Male SD rats were randomly divided into control(CON) group, potassium oxonate(PO) group and high temperature-humidity(HTH) group, 6 rats each. The experiment lasted for 6 consecutive weeks. Rats from PO group was given 250 mg/kg PO by gavage every day. The rats from HTH group were treated with a special thermostatic incubator for one hour each day after gavaging 250 mg/kg PO. Serum uric acid, creatinine and other indicators were detected every 2 weeks. After 6 weeks, the kidney tissues were collected. The morphological changes and urate crystal deposition of kidney tissues were observed by hematoxylin-eosin staining, Masson′s trichrome staining and gomori staining, while the ultramicrostructural changes of kidney were observed by transmission electron microscope.Results:Two weeks after the experiment, the average serum uric acid values of PO group and HTH group increased significantly, HTH group was higher than PO and CON groups[(133.9±17.8), (107.6±12.4), and (85.7±4.1) μmol/L, P=0.001]. And after 6 weeks, the HTH group was still higher than the other two groups[(115.1±27.8), (82.7±13.9), and (72.9±17.8) μmol/L, P=0.008). The average serum creatinine in HTH group was slightly higher than that in PO group and CON group at 6 weeks[(46.2±4.7), (38.1±6.0), and (28.3±6.3) μmol/L, P=0.001]. Light microscope showed partial renal tubular dilatation in PO group, but renal tubular epithelial cells swelling and inflammatory cells infiltration were more significant in HTH group. The ultrastructural changes such as glomerular podocyte swelling were found in HTH group by transmission electron microscope. Conclusion:In this study, we had successfully established a hyperuricemia rat model by simulating the high temperature-humidity environment combined with potassium oxyzinate after 2 weeks of experiment. After 6 weeks of modeling, it was found that the high temperature-humidity induced rat models possessed a relatively higher and stabler serum uric acid level than that of the traditional chemical medicine induced rats. The method can be applied to the research of pathogenesis and pharmacotherapy of hyperuricemia caused by high temperature-humidity environment.

The Spike protein of SARS-CoV-2 impairs lipid metabolism and increases susceptibility to lipotoxicity: implication for a role of Nrf2

Background/objectivesCoronavirus disease 2019 (COVID-19) patients exhibit lipid metabolic alterations, but the mechanism remains unknown. In this study, we aimed to investigate whether the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impairs lipid metabolism in host cells. MethodsA Spike cell line in HEK293 was generated using the pcDNA vector carrying the Spike gene expression cassette. A control cell line was generated using the empty pcDNA vector. Gene expression profiles related to lipid metabolic, autophagic, and ferroptotic pathways were investigated. Palmitic acid (PA)-overload was used to assess lipotoxicity-induced necrosis. ResultsAs compared with controls, the Spike cells showed a significant increase in lipid depositions on cell membranes as well as dysregulation of expression of a panel of molecules involved lipid metabolism, autophagy, and ferroptosis. The Spike cells showed an upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), a multifunctional transcriptional factor, in response to PA. Furthermore, the Spike cells exhibited increased necrosis in response to PA-induced lipotoxicity compared to control cells in a time- and dose-dependent manner via ferroptosis, which could be attenuated by the Nrf2 inhibitor trigonelline. ConclusionsThe Spike protein impairs lipid metabolic and autophagic pathways in host cells, leading to increased susceptibility to lipotoxicity via ferroptosis which can be suppressed by a Nrf2 inhibitor. This data also suggests a central role of Nrf2 in Spike-induced lipid metabolic impairments. HighlightsO_LIThe Spike protein increases lipid deposition in host cell membranes C_LIO_LIThe Spike protein impairs lipid metabolic and autophagic pathways C_LIO_LIThe Spike protein exaggerates PA-induced lipotoxicity in host cells via ferroptosis C_LIO_LINrf2 inhibitor Trigonelline can mitigate the Spike protein-induced necrosis C_LI

Spike Protein of SARS-CoV-2 Activates Macrophages and Contributes to Induction of Acute Lung Inflammations in Mice

BackgroundCoronavirus disease 2019 (COVID-19) patients exhibit multiple organ malfunctions with a primary manifestation of acute and diffuse lung injuries. The Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to mediate viral entry into host cells; however, whether it can be cellularly pathogenic and contribute to pulmonary hyper-inflammations in COVID-19 is not well known. Methods and FindingsIn this study, we developed a Spike protein-pseudotyped (Spp) lentivirus with the proper tropism of SARS-CoV-2 Spike protein on the surface and tracked down the fate of Spp in wild type C57BL/6J mice receiving intravenous injection of the virus. A lentivirus with vesicular stomatitis virus glycoprotein (VSV-G) was used as the control. Two hours post-infection (hpi), Spp showed more than 27-75 times more viral burden in the lungs than other organs; it also exhibited about 3-5 times more viral burden than VSV-G lentivirus in the lungs, liver, kidney and spleen. Acute pneumonia was evident in animals 24 hpi. Spp lentivirus was mainly found in LDLR+ macrophages and pneumocytes in the lungs, but not in MARC1+ macrophages. IL6, IL10, CD80 and PPAR-{gamma} were quickly upregulated in response to infection of Spp lentivirus in the lungs in vivo as well as in macrophage-like RAW264.7 cells in vitro. We further confirmed that forced expression of the Spike protein in RAW264.7 cells could significantly increase the mRNA levels of the same panel of inflammatory factors. ConclusionsOur results demonstrate that the Spike protein of SARS-CoV-2 alone can induce cellular pathology, e.g. activating macrophages and contributing to induction of acute inflammatory responses.

Follow-up study on serum cholesterol profiles in recovered COVID-19 patients

COVID-19 patients develop hypolipidemia. However, it is unknown whether lipid levels have improved in recovered patients. In this study, a 3-6 month follow-up study was performed to examine serum levels of laboratory values in 107 discharged COVID-19 patients (mild = 59; severe/critical = 48; diagnoses on admission). 61 patients had a revisit chest CT scan. A Wilcoxon signed-rank test was used to analyze changes in laboratory values. LDL-c and HDL-c levels were significantly higher at follow-up than at admission in severe/critical cases (p < 0.05). LDL-c levels were significantly higher at follow-up than at admission in mild cases (p < 0.05). With adjustment of the factor of traditional Chinese medicine, LDL-c and HDL-c levels were significantly improved at follow-up than at admission in severe/critical cases (p < 0.05). Increases in HDL-c significantly correlated with increases in numbers of white blood cells (p<0.001) and decreases in levels of C-reactive protein (p < 0.05) during patients recovery. Residue lesions were observed in CT images in 69% (42 of 61) of follow-up patients. We concluded that improvements of LDL-c, HDL-c and incomplete absorption of lung lesions were observed at follow-up for recovered patients, indicating that a long-term recovery process could be required.

Comparative study on EEG and neuroimaging of patients with cerebral cysti-cercosis before and after treatment / 中国血吸虫病防治杂志

Objective To study the changes of cerebral function and pathological morphology before and after the antiparasit-ic treatment with albendazole and praziquantel in patients with cerebral cysticercosis. Methods The data of EEG and neuroimag-ing of 412 patients with cerebral cysticercosis were retrospectively analyzed. Results Before the treatment,the mild abnormali-ty,moderate abnormality,and severe abnormality were observed in 40.53%,45.63% and 13.84% of the patients respectively, which mainly showed the diffuse or focal irregular slow waves,or epileptiform discharges found in the abnormal brain waves. CT/MRI manifestation could be divided into six types,including single sacculus type(23.59%),multiple sacculus type(44.42%), encephalitis type(13.59%),coexistence of macrocyst and sacculus type(4.85%),calcification type(2.18%),and mixed type (11.41%). After 3 courses of the treatment,the normal and improved EEGs were observed in 79.85%and 20.15%,respectively. CT/MRI showed the foci being all absorbed(77.18%),being most absorbed(20.63%),and being no changes(20.18%)which were calcified focus. When cerebral cysticercosis were in acute stage(the single and multiple sacculus type,encephalitis type, and macrocyst and sacculus coexistence type),the therapeutic effect was good;while in the mixed type,the therapeutic effect was relatively poor. If cysticercosis were in the calcification stage,the patients only needed the heteropathy. Conclusions In the pa-tients with cerebral cysticercosis,EEGs show the mild to severe abnormalities,and CT/MRI mainly shows the multiple sacculus type. After the treatment,the abnormal EEGs are gradually recovered and the low density foci can be all absorbed,but some calci-fied focus still exist in some patients.

Experimental study on cross-resistance of Culex pipiens pallens to 3 kinds of chemical pesticides / 中国血吸虫病防治杂志

Objective To understand the cross-resistance of Culex pipiens pallens to common pesticides,so as to provide the evidence for improving the application of chemical pesticides. Methods The IV instar larvae of DDVP-resistant,propoxur-resistant and cypermethrin-resistant strains as well as the sensitive strain of Culex pipiens pallens were collected to detect the re-sistance to DDVP,propoxur and cypermethrin based on the WHO bioassay method. Results The resistance coefficients of DDVP-resistant strain to DDVP,propoxur and cypermethrin were 14.47,8.96 and 207.27 respectively. The resistance coeffi-cients of propoxur-resistant strain to DDVP,propoxur and cypermethrin were 3.27,6.93 and 8.65 respectively. The resistance coefficients of cypermethrin-resistant strain to DDVP,propoxur and cypermethrin were 2.93,1.61 and 501.11 respectively. Con-clusion The resistance and cross-resistance could be generated during the long-term application of a single kind of chemical pesticide,and we should pay more attention to the varieties and dosages of them.

The clinical application of cryoplasty for lower extremity arterial occlusive disease / 中华放射学杂志

ObjectiveTo observe the short term efficacy and safety of cryoplasty in treatment of lower extremity arterial occlusive disease. MethodsTwenty five patients (27 limbs) scheduled for lower extremity artery balloon angioplasty were randomized to cryoplasty [ group CRYO, 10 patients with 8 male,age ( 76 ± 8 ) years]or conventional balloon angioplasty [ group COBA, 15 patients with 13 male, age ( 68 ±4) years], In CRYO group, the average lesion length and stenosis were (6.7 ±0.9) cm and, (91±6)％, respectively. The average ankle-brachial index (ABI) was 0. 46 ±0. 07 before treatment. According to Fontaine clinical stages, 7 patients (7/10) in this group were staged Ⅱ and the other 3 (3/10) were staged Ⅲ. According to Trans Atlantic Inter Society Consensus (TASC), 8 patients (8/10) were classified as TASC type A and the other 2 (2/10) were TASC type B. In COBA group, the average lesion length and stenosis were (6. 5 ± 0. 7 ) cm and ( 89 ± 7 ) ％, respectively. The average ABI was 0. 48 ± 0. 08 before treatment.According to Fontaine clinical stages, 13 patients (13/15) were stagedⅡand the other 2(2/15) were staged Ⅲ. And, according to TACS, 13 patients (13/15) were classified as TASC type A and the other 2 (2/15) were TASC type B. The clinical symptoms and signs had no significant difference between the two groups ( P ＞ 0. 05 ).Clinical status was evaluated according to Rutherford classification.The clinical efficacy on the 2nd and 30 th day after the operation was compared using analysis of variance with repeated measurements. ResultsTechnical success was achieved in all patients both in CRYO group (10/10) and in COBA group (15/15). None patient in CRYO group occurred postoperative complication.One patient in COBA group ( 1/15 ) occurred vessel wall dissection. In CRYO group, clinical status were remarkably improved in 8 patients (8/10) and moderately improved in 2 patients (2/10) ; while, in COBA group, they were remarkably improved in 13 patients ( 13/15 ) and moderately improved in 2 patients ( 2/15 ). The average ABI was 0. 84 ± 0. 04 in group CRYO and 0. 84 ± O. 05 in group COBA ( P ＝ 0. 20).The average stenosis was (29 ± 4) ％ in group CRYO and (32 ± 4) ％ in group COBA ( P ＝ 0. 55 ). No significant difference was detected between the two groups.Both the average ABI and stenosis presented statistically significant difference between pre-operation and post-operation in both groups ( P ＜ 0. 01,respectively).Conclusions Cryoplasty is safe for the treatment of lower extremity arterial occlusive disease, which showed a good short-term result in this research.