AIM:To investigate the effect of hypericin(Hyp)on the heart of rats with myocardial ischemia-re-perfusion injury(MIRI),and to explore its mechanism.METHODS:Thirty SPF male SD rats were divided into 5 groups:sham group,MIRI group,low-dose Hyp(L-Hyp)group(MIRI+L-Hyp group),high-dose Hyp(H-Hyp)group(MIRI+H-Hyp group),and positive control trimetazidine(TMZ)group(MIRI+TMZ group),with 6 rats in each group.Apart from the sham group,the MIRI model was established by ligating the anterior descending branch of the left coronary artery and then recanalizing it in the remaining four groups of rats.The success of the modeling was determined by monitor-ing the electrocardiogram.We assessed the cardiac function in rats using echocardiography.TTC staining was employed to measure the area of myocardial infarction in rats,and HE staining was utilized to observe the morphological traits of rat myocardium.We assayed the activities of lactate dehydrogenase(LDH)and superoxide dismutase(SOD)and the levels of malondialdehyde(MDA)in rat serum using biochemical kits.ELISA kits were applied to assess the contents of cardiac troponin I(cTnI)and reactive oxygen species(ROS)in rat serum.Western blot analysis was perfomed to measure the pro-tein expression levels of AMPK,p-AMPK,Nrf2,and HO-1 in rat myocardial tissues.RESULTS:The rats in MIRI group exhibited increased myocardial tissue injury,larger myocardial infarction areas,decreased left ventricular ejection fraction(LVEF),and reduced left ventricular fractional shortening(LVFS)compared with sham group,as shown by echo-cardiography.Additionally,there were increases in LDH activity,cTnI,MDA and ROS levels,along with significant de-creases in SOD activity,and p-AMPK,Nrf2 and HO-1 protein levels(P<0.05).Compared with MIRI group,the rats in MIRI+L-Hyp,MIRI+H-Hyp and MIRI+TMZ groups showed decreased myocardial histopathological damage and reduced myocardial tissue infarction area,increased LVEF and LVFS,and lowered serum levels of LDH activity,cTnI,MDA and ROS,while SOD activity,p-AMPK,Nrf2 and HO-1 protein levels were elevated(P<0.05).CONCLUSION:Hypericin attenuates myocardial ischemia-reperfusion injury in rats,possibly by modulating the AMPK/Nrf2/HO-1 signaling path-way.

Objective:To investigate the efficacy and safety of kidney sparing treatment based on Thulium laser ablation and systematic therapy in localized high-risk upper urinary tract urothelial carcinoma (UTUC).Methods:The data of 10 patients with UTUC who received combined treatment based on Thulium laser and systematic treatment from January 2020 to December 2021 in West China Hospital were retrospectively analysed. There were 5 males and 5 females with a median age of 76 (range 52 to 87)years old. Three cases were renal pelvis tumor and 7 cases were ureter tumor including 5 cases in lower ureter and 2 cases in upper and middle ureter. Five cases were with positive urine cytology and 6 cases were with hydronephrosis. One case was muscular invasion UTUC confirmed by biopsy(cT 2+), 7 cases were high-grade invasive urothelial carcinoma (cT 1+), and 2 cases were high-grade papillary urothelial carcinoma (cT a). Among 10 cases, 5 patients refused radical nephroureterectomy(RUN), among whom 3 patients were too old or in poor general condition to tolerate RNU. One case had a solitary kidney and 1 case had bilateral tumours. Patients were treated with Thulium laser tumor ablation under ureteroscopy combined with systemic therapy. The perioperative systemic treatment included platinum-based chemotherapy±immunotherapy, RC48+ immunotherapy, and immunotherapy alone. The postoperative treatment was immunotherapy maintenance±local radiotherapy. Strict follow-up was conducted after the completion of treatment. Results:Nine patients received systemic therapy before ablation. Four cycles of platinum-based chemotherapy (cisplatin in 2 cases, carboplatin in 1 case) were used in 3 cases, and platinum-based chemotherapy + immunotherapy (6 cycles of cisplatin + toripalimab in 1 case, 4 cycles of cisplatin + toripalimab in 1 case, 4 cycles of carboplatin+ trelizumab in 1 case) was used in 3 cases, four cycle of RC48 + immunotherapy (toripalimab or trelizumab) were used in 2 cases, and four cycles of immunotherapy (toripalimab) were used in 1 case. The operations of 10 cases were successfully completed without serious complications during the perioperative period and the laser working time (42.4 ± 15.2) min. Of the 10 cases, 4 achieved complete ablation at the first ablation, and 6 patients had incomplete ablation. Among them, 2 patients achieved clinical complete remission after 1-2 cycles of systemic therapy, and 4 patients achieved complete ablation after Thulium laser ablation again.All the 10 patients were treated with immunotherapy for 1 year, and 2 of them received additional adjuvant radiotherapy. The patients were followed-up for median 40 months(range 26 to 53 months). Recurrence occurred in 5 cases, of which 3 cases underwent salvage nephroureterectomy and 2 cases underwent Thulium laser ablation under ureteroscopy again. Five patients had no tumor recurrence. None of the 10 patients had distant metastasis. At the last follow-up, 1 patient died of complications and 6 patients kept the affected kidney alive. Perioperative complications including macroscopic hematuria (8 cases), fever (3 cases), the long-term complications of ureter stenosis (4 cases).Conclusions:For localized high-risk UTUC, local Thulium laser ablation combined with systemic therapy can achieve good tumor control while preserving the affected kidney in selected patients, and its potential application value should be further evaluated.

【Objective】 To study the effect of macrophage mediator 1 (MED1) deficiency on atherosclerosis in female mice. 【Methods】 ApoE knockout (ApoE^-/-), LDLR knockout (LDLR^-/-), MED1^fl/fl, and macrophage MED1 knockout (MED1^△Mac) mice were recruited in the study. Two types of mouse model were constructed:ApoE and macrophage MED1 double knockout (MED1^△Mac/ApoE^-/-) mice and their littermate controls (MED1^fl/fl/ApoE^-/-). ② LDLR knockout (LDLR^-/-) mice receiving bone marrow from MED1^△Mac (MED1^△Mac→LDLR^-/-) or MED1^fl/fl (MED1^fl/fl→LDLR^-/-) mice. Female mice from these two models were fed a Western diet (21% fat and 0.15% cholesterol) for 12 weeks to promote the development of atherosclerosis. Body weight, total cholesterol (TC), and total triglyceride (TG) content in plasma were measured dynamically. After Western diet feeding for 12 weeks, aortic tree and aortic root were collected and hematoxylin-eosin (H&E) and oil red O staining were performed. 【Results】 Plasma TC and TG did not significantly differ between MED1^fl/fl/ApoE^-/- control group and MED1^△Mac/ApoE^-/-experimental group. However, the plaque area in aortic tree and aortic root was significantly increased in MED1^△Mac/ApoE^-/-mice. Moreover, compared with that in MED1^fl/fl→LDLR^-/- control group, the plaque area of aortic tree and aortic root had an increasing trend in MED1^△Mac→LDLR^-/- mice group. 【Conclusion】 MED1 deficiency in macrophages promotes the development of atherosclerosis in female ApoE or LDLR knockout mice.

Objective:To investigate the effects of different doses of vitamin D diet early in life on airway inflammation in different endotypes of asthma mice models.Methods:In the Animal House of Shanghai General Hospital of Nanjing Medical University in June 2022, the BALB/c mice with 14 d pregnant were selected, the offspring mice were divided into vitamin D sufficient group and vitamin D deficient group by random number table method with 12 each. The mice in the vitamin D sufficient group were given a feed with sufficient vitamin D content, while the mice in the vitamin D deficient group were given a feed without vitamin D. At the age of 8 weeks, the mice were sensitized and stimulated with ovalbumin to establish a T2 type asthma model, while the mice were sensitized and stimulated with ovalbumin combined with ozone exposure to establish a non-T2 type asthma model, with 6 mice in each model. The level of serum 25 hydroxy vitamin D 3 was detected by enzyme-linked immunosorbent assay (ELISA) method. The lung tissue was stained with HE to evaluate the inflammatory response score and calculate the eosinophils density and neutrophils density. In bronchoalveolar lavage fluid (BALF), the expression levels of interleukin (IL)-4, IL-6, IL-10 and IL-17A, the inflammatory cell count (total cell count, neutrophil count and eosinophil count) were detected. Results:The 25 hydroxy vitamin D 3 in T2 type asthma mice and non-T2 type asthma mice of vitamin D deficient group were significantly lower than that in vitamin D sufficient group: (8.12 ± 1.72) μg/L vs. (26.63 ± 2.54) μg/L and (6.86 ± 1.65) μg/L vs. (23.81 ± 3.09) μg/L, and there was statistical difference ( P<0.01). The inflammatory response score in non-T2 type asthma mice of vitamin D deficient group was significantly higher than that in non-T2 type asthma mice of vitamin D sufficient group: (2.58 ± 0.49) scores vs. (1.83 ± 0.21) scores, and there was statistical difference ( P<0.05), there was no statistical differences in inflammatory response score in T2 type asthma mice between two groups ( P>0.05). The neutrophils density and eosinophils density in T2 type asthma mice and non-T2 type asthma mice of vitamin D deficient group were significantly higher than those in vitamin D sufficient group, T2 type asthma mice: (20.30 ± 1.95) cells/100 μm vs. (12.58 ± 1.04) cells/100 μm and (5.25 ± 0.62) cells/100 μm vs. (3.15 ± 0.35) cells/100 μm; non-T2 type asthma mice: (53.48±5.19) cells/100 μm vs. (33.80 ± 2.74) cells/100 μm and (3.00 ± 0.29) cells/100 μm vs. (2.17 ± 0.21) cells/100 μm, and there were statistical differences ( P<0.01 or <0.05). The BALF total cell count in T2 type asthma mice and non-T2 type asthma mice of vitamin D deficient group was significantly higher than that in vitamin D sufficient group, the BALF eosinophil count in T2 type asthma mice of vitamin D deficient group was significantly higher than that in T2 type asthma mice of vitamin D sufficient group, the BALF neutrophil count in non-T2 type asthma mice of vitamin D deficient group was significantly higher than that in T2 type asthma mice of vitamin D sufficient group, and there were statistical differences ( P<0.01); there was no statistical difference in BALF neutrophil count in T2 type asthma mice between two groups ( P>0.05); there was no statistical difference in BALF eosinophil count in non-T2 type asthma mice between two groups ( P>0.05). The BALF total cell count and neutrophil count in non-T2 type asthma mice of both groups were significantly higher than those in T2 type asthma mice, but the BALF eosinophil count in T2 type asthma mice was significantly higher non-T2 type asthma mice, and there were statistical differences ( P<0.05). The BALF IL-4, IL-6 and IL-17A in T2 type asthma mice and non-T2 type asthma mice of vitamin D deficient group were significantly higher than those in vitamin D sufficient group, the BALF IL-10 was significantly lower than those in vitamin D sufficient group, and there were statistical differences ( P<0.01 or <0.05). In vitamin D deficient group, the BALF IL-4 in non-T2 type asthma mice was significantly lower than that in T2 type asthma mice, the BALF IL-6 and IL-17A were significantly higher than those in T2 type asthma mice, and there were statistical differences ( P<0.05); in vitamin D sufficient group, the BALF IL-6 and IL-17A in non-T2 type asthma mice were significantly higher than those in T2 type asthma mice, and there were statistical differences ( P<0.05). Conclusions:Vitamin D deficiency is involved in different mechanisms of airway inflammation in T2 type asthma and non-T2 type asthma, and this effect may be more obvious for non-T2 type asthma.

Objective:To evaluate the efficacy and safety of allopurinol in the treatment of chronic kidney disease.Methods:The databases of Embase, PubMed and the Cochrane library were searched for randomized controlled trials of allopurinol in patients with chronic kidney disease. According to the Cochrane system evaluation method, two evaluators independently screened the literature and extracted the data, and analyzed the results with Revman 5.3 software.Results:Finally, 10 articles were included, including 940 patients (472 in the experimental group and 468 in the control group). Meta analysis showed that allopurinol treatment could reduce blood uric acid ( MD=-2.40, 95% CI: -2.74--2.05, P<0.01), 24-hour urinary protein ( MD=-0.61, 95% CI: -1.17--0.06, P=0.03) and increase estimation of glomerular filtration rate(eGFR) ( MD=2.51, 95% CI: 1.86-3.17, P<0.01). There was no significant difference in adverse events between the experimental group and the control group ( OR=1.40, 95% CI: 0.61-3.19, P=0.42), but allopurinol treatment could reduce the risk of cardiovascular events ( OR=0.58, 95% CI: 0.38-0.89, P=0.01). Conclusions:Allopurinol treatment of chronic kidney disease can reduce urinary protein, improve eGFR, and reduce the risk of cardiovascular events.

SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively throughout the world since its first outbreak in December,2019.Whether the transmissibility and pathogenicity of SARS-CoV-2 in humans after zoonotic transfer are actively evolving,and driven by adaptation to the new host and environments is still under debate.Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend,and providing guidance for disease control and treatments.Interrogating novel strategies for identifying natural selection using within-species polymorphisms and 3,674,076 SARS-CoV-2 genome sequences of 169 countries as of December 30,2021,we demonstrate with popula-tion genetic evidence that during the course of SARS-CoV-2 pandemic in humans,1)SARS-CoV-2 genomes are overall conserved under purifying selection,especially for the 14 genes related to viral RNA replication,transcription,and assembly;2)ongoing positive selection is actively driving the evolution of 6 genes(e.g.,S,ORF3a,and N)that play critical roles in molecular processes involving pathogen-host interactions,including viral invasion into and egress from host cells,and viral inhi-bition and evasion of host immune response,possibly leading to high transmissibility and mild symptom in SARS-CoV-2 evolution.According to an established haplotype phylogenetic relation-ship of 138 viral clusters,a spatial and temporal landscape of 556 critical mutations is constructed based on their divergence among viral haplotype clusters or repeatedly increase in frequency within at least 2 clusters,of which multiple mutations potentially conferring alterations in viral transmis-sibility,pathogenicity,and virulence of SARS-CoV-2 are highlighted,warranting attention.

Objective:To explore the changing characteristics of self-efficacy, social support, psychological stress in patients with osteoporotic vertebral compression fractures (OVCFs) receiving conservative treatment at different treatment stages and their correlations with the recovery of lower back function.Methods:A total of 116 patients with acute OVCFs who were admitted to the Affiliated Hospital of Medical School, Ningbo University were selected from January 2017 to May 2019. Oswestry Disability Index (ODI) Questionnaire, General Self Efficacy Scale (GSES) , Perceived Social Support Scale (PSSS) and Perceived Stress Scale (PSS) were used to assess the lower back function, self-efficacy, social support and psychological stress of OVCFs patients. Questionnaires were filled out during outpatient reexamination or in-home follow-up, and the evaluation time was at the time of treatment and 1, 3, 6, and 12 months after conservative treatment. Analysis of variance and SNK- q test were used to explore the characteristics of each score over time, and linear regression analysis was used to explore the effects of GSES, PSSS, and PSS on ODI. Results:With the prolongation of treatment time, ODI, GSES, PSSS and PSS scores of OVCFS patients under conservative treatment showed a downward trend, and the scores at 3, 6 and 12 months after treatment were lower than those at 1 month after conservative treatment ( P<0.05) . The scores at 6 and 12 months after conservative treatment were lower than those at 3 months after conservative treatment ( P<0.05) . The scores at 12 months after conservative treatment were lower than that those at 6 months after conservative treatment ( P<0.05) . GSES, PSSS (total score, in-family support, out-of-family support) and PSS were independent influencing factors of ODI at one month after treatment ( P<0.05) . GSES, PSSS (total score, in-family support) and PSS were the influencing factors of ODI at 3 months after treatment ( P<0.05) . Conclusions:The self-efficacy and social support of conservatively treated patients with OVCFs are positively correlated with their lower back function, while psychological stress will reduce lower back function of such patients. It is suggested to add these non-physical factors to the rehabilitation nursing model and take appropriate intervention measures.

OBJECTIVE： To systematically evaluate the efficacy and safety of cyclosporin combined with glucocorticoid versus cyclophosphamide combined with glucocorticoid in the treatment of membranous nephropathy （MN）. METHODS： Retrieved from Embase， Medline， CNKI， VIP and Wanfang database， RCTs about cyclosporin combined with glucocorticoid （trial group） versus cyclophosphamide combined with glucocorticoid （control group） in the treatment of MN were collected. Meta-analysis was conducted by using Rev Man 5.3 statistical software after literature screening， data extraction and quality evaluation with Jadad scale. RESULTS： Totally 6 RCTs were included， involving 312 patients in total. Results of Meta-analysis showed that remission rate 3 months after treatment [OR＝3.42，95％CI（2.05，5.71），P＜0.000 01] and relapse rate [OR＝3.12，95％CI（1.45，6.70），P＝0.004]， leukocyte count 12 months after treatment [MD＝1.77，95％CI（0.96，2.58），P＜0.000 1] in trial group were significantly higher than control group. There was no statistical significance in remission rate 6 months after treatment [OR＝2.06，95％CI（0.80，5.30），P＝0.13] and remission rate 12 months after treatment [OR＝1.30，95％CI（0.68，2.48），P＝0.42]， blood creatinine level 3 months after treatment [MD＝－1.55，95％CI（－6.72，3.62），P＝0.56] and blood creatinine level 6 months after treatment [MD＝－1.21，95％CI（－5.96，3.54），P＝0.62]， cholesterol level 12 months after treatment [MD＝－0.77，   95％CI（－1.81，0.28），P＝0.15] or ALT level[MD＝－0.40，95％CI（－4.38，3.58），P＝0.98] between 2 groups. ADR were reported in 5 RCTs， but their results were different. CONCLUSIONS： Long-term efficacy of cyclosporine combined with corticosteroid is similar to that of cyclophosphamide combined with corticosteroid in the treatment of MN. Cyclosporin combined with glucocorticoid has a faster effect， but a higher relapse rate.

Objective To investigate the predominant genotypes and epidemiological characteristics of human adenovirus (HAdV) in pediatric community-acquired pneumonia (CAP) in China.Methods This was a repeated cross sectional study.Between November 2014 and November 2016,nasopharyngeal aspirates (NPAs) or throat swabs from each hospitalized pediatric patients diagnosed as CAP in 12 hospitals in Northern and Southern China were collected.Respiratory specimens were screened for 18 respiratory viruses including HAdV by using Luminex xTAG RVP Fast V2 multiplex Assay.Typing of HAdV and analysis for the epidemiological characteristic of HAdV were performed.Results (1) A total of 2 723 hospitalized pediatric patients with CAP were enrolled in this study and 156 (5.7％,156/2 723) respiratory specimens were positive for HAdV,and 74 (6.6％,74/1 128) and 82 (5.1％,82/1 595) were in Northern and Southern China,respectively.There was no significant difference in the positive detection rate between the Northern and Southern China.(2) In Northern China,the HAdV positive rate of children at the age of ＜6 months,6 months-＜1 years,1-＜3 years,3-＜5 years and ≥5 years was 5.9％(6/101),6.7％(7/104),10.3％(34/331),4.1％(11/266) and 4.9％(16/326),respectively,and the incidence of HAdV infection peaked in children aged 1-3 years (x2=11.511,P=0.021).While in Southern China the HAdV positive rate of children at the age of ＜6 months,6 months-＜1 years,1-＜3 years,3-＜5 years and ≥5 years was 2.2％ (7/312),4.6％ (12/259),6.3％ (31/494),7.3％ (18/245) and 4.9％(14/285),respectively.There was no significant difference in the positive detection rate among age groups.(3) In 2015,the highest detection rate of HAdV in northern China was 12.5％ (25/200) in winter,and in Southern China was 6.7％ (35/525) in spring and 5.3％ (19/357) in summer.(4) In 108 cases of HAdV positive specimens typing was done and 80 in cases classification was successfully performed.Totally 7 genotypes of HAdV,including HAdV-3 (n=32),HAdV-7 (n=9),HAdV-1 (n=12),HAdV-2 (n=15),HAdV-5 (n=10),HAdV-6 (n=1) and HAdV-4 (n=1),were detected.The predominant HAdV genotypes were HAdV-3 (30.8％,8/26) and HAdV-7 (26.9％,7/26) in Northern China,while HAdV-3 (44.4％,24/54) and HAdV-2 (22.2％,12/54) were the most prevalent genotypes in Southern China.Conclusions HAdV is an important viral pathogen in pediatric CAP.The predominant HAdV genotypes and peak seasons of HAdV infections were different between Northern and Southern China.The predominant HAdV genotypes were HAdV-3 and HAdV-7 in Northern China,while HAdV-3 and HAdV-2 in Southern China.The peak season of HAdV infections was winter in Northern China.However,HAdV infections are more common in spring and summer in Southern China.

Objective To evaluate the accuracy of different biomarkers for early diagnosis of acute kidney injury ( AKI ) in the patients undergoing cardiovascular surgery under cardiopulmonary bypass ( CPB) . Methods A total of 200 patients, aged 22-86 yr, weighing 46-87 kg, scheduled for elective cardiovascular surgery under CPB, were enrolled in this study. The concentration of serum creatinine was determined at 1 day before operation and 1-7 days after operation. At 1 day before operation and 0, 2, 6 and 12 h after operation, the concentrations of urine neutrophil gelatinase-associated lipocalin (NGAL), cystatin C ( Cys C) , tissue inhibitor of matrix metalloproteinase type 2 ( TIMP-2) and insulin-like growth factor binding protein-7 ( IGFBP-7) were determined. The TIMP-2 and IGFBP-7 product ( TI) was calcu-lated. AKI was diagnosed after surgery according to Kidney Disease Improving Global Outcomes criteria. The receiver operating characteristic curve was plotted, and the area under receiver operating characteristic curve ( AUC) was calculated. Results The incidence of AKI was 20. 5％. The AUC of AKI diagnosed by the concentration of urine NGAL was 0. 689, 0. 709, 0. 713 and 0. 803 at 0, 2, 6 and 12 h after opera-tion, respectively ( P<0. 05) . The AUC of AKI diagnosed by the concentration of urine Cys C was 0. 639, 0. 762, 0. 774 and 0. 812 at 0, 2, 6 and 12 h after operation, respectively ( P<0. 05) . The AUC of AKIdiagnosed by TI was 0. 687, 0. 721, 0. 740 and 0. 779 at 0, 2, 6 and 12 h after operation, respectively ( P<0. 05) . The AUC of AKI diagnosed by combined three indices the parallel test was 0. 694, 0. 773 and 0. 794 at 0, 2 and 6 h after operation, respectively ( P<0. 05) . The AUC of AKI diagnosed by the serial test was 0. 610, 0. 631 and 0. 667 at 0, 2 and 6 h after operation, respectively. Conclusion Urine NGAL or Cys C concentrations or TI single detection and parallel test have a certain accuracy for early diag-nosis of AKI in the patients undergoing cardiovascular surgery under CPB.