The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

ObjectiveTo explore the risk factors of stroke， and to provide reference for the prevention and health management of stroke. MethodsFrom February 2022 to March 2022， four community residents over 60 years old with stroke in Shanghai were randomly selected as the case group （n=100）， and non-stroke residents were selected as the control group （n=100）. The survey was in the form of questionnaires to record and compare the age， body mass index （BMI）， blood lipids， blood pressure-related indicators， family history of other diseases， living habits， mood and sleep conditions of all subjects. The value of predicting the incidence of stroke among the elderly in Shanghai community was analyzed by receiver operating characteristic （ROC）， and the influencing factors of stroke were analyzed by logistic model. ResultsBMI， hypertension， heart disease， diabetes， transient ischemic attack （TIA）， dyslipidemia， family history of stroke， smoking， lack of exercise or only light physical labor， SBP， DBP， TG levels were significantly higher in the case group （P<0.05）. The level of HDL-C was significantly lower than that in the control group （P<0.05）. BMI， SBP， DBP， TG， HDL-C predicted the incidence of stroke by ROC analysis （P<0.05）. Logistic regression analysis showed that BMI≥23.820 kg·m^-2， heart disease， diabetes， TIA， dyslipidemia， family history of stroke， smoking， lack of exercise or only light physical labor， SBP≥139.535 mmHg， DBP≥89.605 mmHg， TG≥1.565 mmol·L^-1 and HDL-C≤1.105 mmol·L^-1 were risk factors for stroke （P<0.05）. ConclusionPhysical health status including blood lipids and blood pressure， family history of certain diseases， and living habits could be important risk factors for stroke in the elderly in Shanghai community. Preventive intervention measures for the above factors have important clinical significance.

Objective:To compare the efficacy of ultrasound combined with endoscopy and ultrasound combined with X-ray guided percutaneous nephrolithotomy(PCNL) in the treatment of complex renal calculi.Methods:The clinical data of 119 patients with complex kidney stones treated by ultrasound combined with endoscopy or ultrasound combined with X-ray guided PCNL in the Second Affiliated Hospital of Anhui Medical University from March 2019 to February 2022 were analyzed retrospectively. According to different guidance methods, they were divided into ultrasound combined with endoscopic guidance group and ultrasound combined with X-ray guidance group.There was no significant difference in age [(53.9±14.2) years vs. (55.6±13.5) years], gender (male/female: 38/21 vs. 30/30), body mass index [(25.0±3.7) kg/m 2 vs. (24.8±3.8)kg/m 2], stone location (left/right: 34/25 vs. 31/29), maximum diameter of renal stones [(31.9±8.3)mm vs. (33.9±13.5)mm], kidney stones maximum cross-sectional area [(601.5±242.5)mm 2 vs. (632.6±278.9)mm 2], number of renal calices involved (3.5±0.9 vs. 3.6±1.3), S. T.O.N.E. scores (9.4±1.0 vs. 9.7±1.4), Guy's grade(Ⅲ/Ⅳ: 45/14 vs. 41/19), preoperative hemoglobin [(125.2±21.5)g/L vs. (125.6±18.4)g/L], serum creatinine[(89.1±33.8) μmol/L vs. (81.9±27.1) μmol/L], urinary tract infection (43/59 vs. 47/60)and positive urinary bacterial culture (12/59 vs.11/60) between the two groups(all P>0.05). The patients in the ultrasound combined with endoscopic guidance group were placed in the modified prone split-leg position. Flexible ureteroscope retrograde into the renal pelvis, combined with ultrasound to determine the best puncture calices. The channels were established and stones were removed under the guidance of ultrasound and endoscopy. In the ultrasound combined with X-ray guidance group, the F5 ureteral catheter was placed retrogradely into the operative side ureter under the lithotomy position. Then the patient changed to prone position and the target calices were punctured under the guidance of ultrasound and X-ray. Through anterograde or retrograde injection of contrast medium, the puncture position was determined to enter in the center of the calicean dome, and the channel establishment process and stone removal are monitored. The operative results and postoperative data were recorded. Results:The average operation time in the ultrasound combined with endoscopic guidance group was significantly shorter than that in the ultrasound combined with X-ray guidance group [(90.2 ± 34.5) min vs. (129.4 ± 43.0) min, P < 0.001]. There was no significant difference in the success rates of initial channel establishment [94.0% (63/67) vs. 87.7% (107/122), P = 0.167], the time of single channel establishment [(7.7 ± 1.9) min vs. (7.7 ± 1.4) min, P =0.765], serum creatinine on the first day after operation[ (89.3±33.6) μmol/L vs. (82.9±27.0) μmol/L, P=0.257] and postoperative hospital stay[(5.3±1.6) d vs.(5.4±1.7) d, P=0.883]. In contrast, patients in ultrasound combined with X-ray guidance group had higher stone free rate [93.3% (56/60) vs. 81.4% (48/59), P=0.049] and lower reoperation rate [3.3% (2/60) vs. 15.3% (9/59), P=0.025]. The mean hemoglobin decrease value of ultrasound combined with endoscopic guidance group was significantly lower than ultrasound combined with X-ray guidance group on the first day after operation [(8.7±6.3) g/L vs. (16.8±6.9) g/L, P<0.001]. The complication rate of ultrasound combined with endoscopic guidance group was significantly lower than that of ultrasound combined with X-ray guidance group [5.1% (3/59) vs. 16.7% (10/60), P = 0.043]. Conclusions:Ultrasound combined with endoscopic guidance PCNL does not need to change body position during operation and has fewer puncture channels, thus saving operation time and reducing complications. It is more suitable for patients with isolated kidney or easy bleeding. Ultrasound combined with X-ray guidance is conducive to the establishment of multi-channel, the stone clearance rate is high and the reoperation rate is low, which is suitable for patients with good health and more renal calices involved with stones.

Objective: To investigate the anti-inflammatory effect of polysaccharide from atractylodes atractylodes(PAMK) on rheumatoid arthritis(RA) rats and its effect on Toll like receptor 4/nuclear factor kappa-B(TLR4/NF-κB) signaling pathway. Methods: RA rat model was induced by type Ⅱ collagen, after successful modeling, the rats were divided into model group, positive drug group(Tripterygium wilfordii polyglycoside tablet), PAMK low-dose and high-dose groups, normal control group was also set, with 12 rats in each group. Tripterygium wilfordii polyglycoside tablets or Atractylodes macrocephala polysaccharide were administered intragastric administration, once a day for 4 weeks. The body weight, paw swelling rate and arthritis index of rats were measured; the thymus index and spleen index were calculated; HE staining was used to observe the histopathological changes of synovial membrane of ankle joint; The levels of interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in serum and synovial tissue of ankle were determined by ELISA; The expression levels of total protein TLR4, MyD88, phosphorylated NF-κB p65(Ser536) and nuclear protein NF-κB p65 in synovial tissue of ankle were detected by Western blot. Results: Compared with the normal control group, synovial hyperplasia and unclear layers were observed in the model group, body weight decreased(P<0.05), paw swelling rate, arthritis index, thymus index and spleen index increased(P<0.05), the levels of IL-1β, IL-6 and TNF-α in serum and synovial tissue of ankle, and the protein expressions of TLR4, MyD88, p-NF-κB p65 and NF-κB p65 in synovial tissue of ankle increased(P<0.05). Compared with model group, the histomathological changes of synovial of ankle joint in positive drug group and PAMK high-dose group were significantly improved, body weight increased(P<0.05), paw swelling rate, arthritis index, thymus index and spleen index decreased(P<0.05), the levels of IL-1β, IL-6 and TNF-α in serum and synovial tissue of ankle, and the protein expressions of TLR4, MyD88, p-NF-κB p65 and NF-κB p65 in synovial tissue of ankle decreased(P<0.05), however, there were no significant differences in the above indexes between PAMK low-dose group and model group(P>0.05). Conclusion PAMK can reduce the inflammatory response and improve RA, and the mechanism may be related to the inhibition of TLR4/NF-κB signaling pathway activation.

Objective:To explore the application of panoramic teaching in clinical practice.Methods:From October 2017 to October 2018, 40 clinical undergraduate interns were collected into the experimental group (panoramic teaching group, n=20) and the control group (traditional teaching group, n=20). The experimental group received panoramic teaching including case teaching, scenario design, and situational simulation, while the control group adopted traditional teaching mode. After the internship, theoretical and operational examinations, and questionnaire survey were conducted to evaluate the teaching effects of the two teaching modes. The data were collected and analyzed by t test using SPSS 16.0 software. Results:The results showed that theoretical examination [(85.4±3.3) vs. (82.5±2.5)] and clinical operational examination [(31.5±3.5) vs. (27.6±2.2)] scores in the panoramic teaching group were significantly higher than that in the traditional teaching group. The questionnaire survey on the satisfactions with teaching mode showed that the panoramic teaching group was significantly better than the traditional teaching group in theory learning [(7.7±0.9) vs. (6.8±0.7)], clinical practice[(7.8±0.9) vs. (6.7±0.7)], learning interest [(8.1±0.7) vs. (6.9±0.7)], self-learning ability [(7.7±0.7) vs. (7.1±0.6)], teacher-student communication ability [(7.6±0.8) vs. (6.8±0.7)], doctor-patient communication ability [(7.5±0.6) vs. (7.0±0.8)], medical humanistic spirit [(7.9±0.7) vs. (6.8±0.7)], group working [(8.2±0.6) vs. (6.5±0.5)], humanistic concern [(8.4±0.5) vs. (7.4±0.7)], and total satisfactions [(8.4±0.5) vs. (7.4±0.7)].Conclusion:Panoramic teaching can significantly improve the theoretical and operational performance of family practice interns, enhance the effect of clinical teaching of family practice, and increase students’ interest and satisfaction in clinical teaching.

Objective: To investigate the feasibility and safety of endoscopic combined simultaneous surgery in the modified prone split-leg position for complex renal calculi with ipsilateral ureteral calculi. Methods: The clinical data of 56 cases patients with simultaneous renal and ureteral stones admitted to the Second Affiliated Hospital of Anhui Medical University from January 2016 to March 2019 were retrospectively analyzed. A retrospective analysis was performed on 56 cases of patients with simultaneous renal and ureteral stones who received surgical treatment between January 2016 and March 2019. According to different surgical methods, 56 cases were divided into the modified prone split-leg position group (observation group) and the traditional pre-lithotomy position followed by prone position group (control group). In observation group, the average age of 11 males and 17 females was (54.1±10.2)years. The mean body mass index was (23.8±2.9) kg/m². The location of stones were left in 14 cases and right in 14 cases. The average kidney involvement calyces number was 2.4±0.7.The mean kidney stones maximum cross-sectional area was (870.9±157.7)m². According to the Guy′s classification system, there were 3 cases of grade Ⅰ, 11 case of grade Ⅱ and 14 case of grade Ⅲ in the observation group. The kidney stones S. T.O.N.E scores was 8.7±1.3 and ureteral calculi S. T.O.N.E scores were 13.1± 1.6.In the control group, the average age was (57.0±8.3)years old. The mean body mass index was (24.4±2.9)kg/m². The average kidney involvement calyces number was 2.1±0.7 and the mean kidney stones maximum cross-sectional area was (808.8±189.6)mm². To the kidney stones Guy′s classification, there were 5 cases of grade Ⅰ, 15 case of grade Ⅱ, 7 case of grade Ⅲ and 1case of grade Ⅳ in the control group. The kidney stones S. T.O.N.E scores were 8.5±0.6 and the ureteral calculi S. T.O.N.E scores were 12.4±1.7. The operation time, calculus clearance rate, postoperative hospitalization days, reoperation rate and severity of complications of Clavien-Dindo were statistically compared between the two groups. Results: The study found that the average operation time in the observation group was significantly shorter than that in the control group [(77.8±27.3)min vs.(94.4±22.8)min](P<0.05). In the observation group, 23 patients had complete removal of renal and ureteral calculi, and 3 patients need reoperation. While in the control group, 16 patients had complete removal and 10 patients had reoperation. There were significant differences between the two groups (P<0.05). According to the complication severity of Clavien-Dindo, there were 4 cases of grade Ⅰ and 1 case of grade Ⅱ in the observation group, 4 cases of grade Ⅰ, 2 case of grade Ⅱ and 2 case of grade Ⅲ in the control group. There were no serious complications of grade Ⅳ and Ⅴ in both groups (P>0.05). In observation group, one case accepted the DSA embolization therapy due to the severe bleeding. One case accepted the puncture drainage due to the perinephric effusion. There was no difference in average postoperative hospital stay between the two groups [(6.5±1.2)d vs.(7.0±2.1)d, P>0.05]. Conclusions It is safe and feasible to treat complex renal calculi with ipsilateral ureteral calculi by endoscopic combined simultaneous surgery in the modified prone split-leg position. One position can solve many problems simultaneously, which can significantly reduce the operation time, increase the stone free rates, reduce the reoperation rate and improve the effectiveness of the operation.

Objective To evaluate the feasibility of peripheral artery CT angiography (CTA)under 70 kV with 50 ml contrast medium on the third-generation dual-source CT. Methods Totally 82 patients who were equally randomized into two groups:70 kV group:the scan was performed under 70 kV tube voltage+50 ml iopromide on the third-generation dual-source CT;and 100 kV group:the scan was performed under 100 kV tube voltage+90 ml iopromide on the second-generation dual-source CT. The CT number of abdominal aorta,bilateral common iliac arteries,common femoral arteries,superficial femoral arteries,popliteal arteries and arteries of the calf were measured and contrast to noise ratio(CNR),signal to noise ratio(SNR)were calculated. The image quality was compared between these two groups. Results The dose-length product was (195.8±46.9)mGy·cm in 70 kV group,which was significantly lower than that in 100 kV group (461.6±57.9)mGy·cm,and was decreased by 57% (t=-22.848,P=0.000). Compared with the 100 kV group,the CT number of the proximal abdominal aorta in 70 kV group was significantly lower(t=-2.502,P=0.014),while the CT number of superficial femoral arteries (t=3.053,P=0.003)and popliteal arteries (t=4.013,P=0.000)was much higher in 70 kV group. SNR and CNR of proximal abdominal aorta,distal abdominal aorta,bilateral common iliac arteries,common femoral arteries,superficial femoral arteries,popliteal arteries and arteries of the calf were significantly lower in 70 kV group than those in 100 kV group (all P<0.05). The artifacts in abdominal aorta (t=2.893,P=0.000)and feet arteries (t=3.776,P=0.000)were higher in 70 kV group than those in 100 kV group,the enhancement of abdominal aorta (t=-1.000,P=0.002)and feet arteries (t=2.893,P=0.010)were lower in 70 kV group,the enhancement of femoral-popliteal arteries (t=-1.000,P=0.000)and arteries of calf (t=4.261,P=0.000)were higher in 70 kV group. Compared with the 100 kV group,the image noise in aorta (t=2.048,P=0.044),femoral-popliteal arteries (t=8.370,P=0.000),arteries of the calf (t=8.315,P=0.000)and feet arteries (t=7.202,P=0.000)were higher in 70 kV group. Conclusion Compared to conventional scan protocol,using 70 kV tube voltage with 50 ml contrast medium to perform peripheral artery CTA can assure the image quality and meanwhile remarkably reduce the radiation dose and the use of contrast medium.
Aorta, Abdominal ; diagnostic imaging ; Arteries ; diagnostic imaging ; Artifacts ; Computed Tomography Angiography ; Contrast Media ; Humans ; Iohexol ; analogs & derivatives ; Leg ; blood supply ; Radiation Dosage ; Signal-To-Noise Ratio ; Tomography, X-Ray Computed

Objective To investigate the efficacy and safety of microsurgery for trigeminal neuralgia (TN) in elderly patients.Methods Totally 143 patients with intractable primary TN who received microsurgery were retrospectively analyzed.There were 92 cases in the elderly group with age of 65-82 years,and the other 51 cases in control group with age of 40-62 years.All the patients in both groups were classified as American Society of Anesthesiologists (ASA) Scale Grade 1 to 3.After suboccipital retrosigmoid craniotomy,microvascular decompression (MVD) was performed in 136patients and partial sensory trigeminal rhizotomy in 7 patients.The complications and efficacy were compared between the two groups.Results 87 cases in the elderly group and 49 cases in control group underwent MVD procedure,complete and part pain relief were achieved in 78 cases and 9 cases in the elderly group,45 cases and 4 cases in control group,respectively.After an average follow-up period of 2.6 and 2.1 years,4 cases (5.1％) among 79 follow-up cases and 3 cases (6.5％) among 46follow-up cases experienced TN recurrences in the elderly and control groups,respectively.No statistically significant differences existed in the efficacy and recurrence rate between the two groups (P＞0.05).There were 3 cases with aseptic meningitis,1 cases with hearing decrease,1 case with cerebrospinal fluid leakage,1 case with pulmonary infection and 1 cases with deliration in the elderlygroup,meanwhile,1 cases with aseptic meningitis,1 case with tinnitus and 1 case with cerebrospinal fluid leakage after surgery in control group (P＞0.05).No facial hypoesthesia appeared in the patients receiving MVD.5 cases in the elderly and 2 cases in control group underwent partial trigeminal rhizotomy with facial hypoesthesia,but the pain released,and no recurrence was found.There were no dead cases in both groups.Conclusions With cautious and proper treatment,microsurgical procedure can be performed safely and effectively in the elderly TN.

OBJECTIVETo observe trinucleotide repeat number, (CTG)n in the 3'-untranslated region of the myotonic protein kinase (MTPK) gene in a clinically suspected woman with myotonic dystrophy (DM) family history and her abortus, in order to confirm the necessity of exerting antenatal examination in patients or suspected individuals with DM family history.

METHODSLong Expand Template polymerase chain reaction (PCR) system was used to analyze CTG trinucleotide repeat numbers located in the 3' untranslated region of MTPK on chromosome 19q13.2-3 in both peripheral white cells and muscles of the suspected mother and the other two DM patients in the family. The tissues of her abortus and blood of a health woman were detected, too.

RESULTSCTG repeats in both peripheral white cells and muscles of the suspected mother and the tissue of abortus were higher than normal range of CTG repeat number. There is no significant difference between blood and muscle samples. High CTG repeats were detected in blood and muscles of the typical DM members in the family, but in the blood sample of control, CTG repeats is normal.

CONCLUSIONCTG trinucleotide analyses and antenatal examination should be done in pregnant with a DM family history, in order to reduce the birth rate of DM offspring.

Adult ; DNA ; analysis ; Female ; Fetus ; metabolism ; Humans ; Myotonic Dystrophy ; diagnosis ; genetics ; Prenatal Diagnosis ; Trinucleotide Repeats

OBJECTIVETo explore the distribution of monoamine oxidase A (MOA-A) EcoRV polymorphism in Shanghai Han population and its possible role in the risk for Parkinson's disease(PD).

METHODSThe MAO-A gene EcoRV polymorphism was detected with PCR-RFLP method in 110 PD patients and 182 healthy controls, furthermore, statistical analysis was performed to investigate association between EcoR V polymorphism and PD onset.

RESULTS(1)Remarkable difference in MAO-A EcoR V polymorphic distribution has been observed between Shanghai Han population and that in North America. (2) Neither allelic frequency nor genotypic frequency in PD cases differs significantly from that in healthy controls regardless of data from male or female subclass.

CONCLUSIONThere may be racial difference in the distribution of the human MAO-A EcoR V (C/T) polymorphism, but the present research does not support the association between this variant and susceptibility to PD in Chinese Han population of Shanghai area.

Adult ; Aged ; Aged, 80 and over ; Alleles ; China ; DNA ; genetics ; metabolism ; Deoxyribonucleases, Type II Site-Specific ; metabolism ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Monoamine Oxidase ; genetics ; Parkinson Disease ; enzymology ; genetics ; Polymorphism, Genetic