Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.
Animals ; Antiviral Agents ; pharmacology ; therapeutic use ; Betacoronavirus ; drug effects ; physiology ; Binding Sites ; drug effects ; Cell Line ; Coronavirus Infections ; drug therapy ; virology ; Crotonates ; pharmacology ; Cytokine Release Syndrome ; drug therapy ; Drug Evaluation, Preclinical ; Gene Knockout Techniques ; Humans ; Influenza A virus ; drug effects ; Leflunomide ; pharmacology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections ; drug therapy ; Oseltamivir ; therapeutic use ; Oxidoreductases ; antagonists & inhibitors ; metabolism ; Pandemics ; Pneumonia, Viral ; drug therapy ; virology ; Protein Binding ; drug effects ; Pyrimidines ; biosynthesis ; RNA Viruses ; drug effects ; physiology ; Structure-Activity Relationship ; Toluidines ; pharmacology ; Ubiquinone ; metabolism ; Virus Replication ; drug effects

Burn medicine of China started in 1958. Great progress has been achieved in discipline construction, scientific research, clinical treatment level, and talent team construction in 60 years. A large number of severely burned patients have been successfully treated, and plans for treatment of burn patients with Chinese characteristics have been established with world-leading treatment level. At the same time, in the continuous improvement of clinical treatment level, extensive experimental researches for the key scientific problems in clinical treatment of burn patients have been conducted, and a large number of innovative research results have been achieved by Chinese burn medicine workers. The theoretical research of burn medicine in China has stepped into advanced ranks of the world. Burn medicine will confront development opportunity and tough challenge in the future. We can take advantage of wound repair of burn discipline to deal with the situation of decreasing incidence of burn and undiminished importance of burn medicine. To establish and improve the chain of burn treatment is an important direction for burn discipline development in the future.

Objective To discuss the outcomes of transvaginal repair and transabdominal repair for complex vesicovaginal fistula (VVF).Methods The data of complex VVF patients undergoing surgical repair in Peking University First Hospital were retrospectively collected between January 2009 and December 2016.The surgical modalities for complex VVF included transvaginal repair with layered closure and transabdominal repair with full thick vascular peritoneal interposition.The subtype distribution of complex VVF in transabdominal repair group and transvaginal repair group were recorded.The present study included 63 complex VVF patients with the median age of 46 years (range 26-60 years).There were 32 cases undergoing transvaginal repair with layered closure and 31 cases undergoing transabdominal repair with full thick vascular peritoneal interposition.The proportion of cases having failed previous repairs was significantly higher in transvagical repair group (30/32 vs.23/31,P =0.034).Compared with patients with transvaginal repair,patients with transabdominal repair tended to have multiple VVF without statistic significance (18.8％ vs.29.0％,P =0.338).Patients with transabdominal repair had larger VVF than patients with transvaginal repair (median:1.0cm vs.0.5cm,P ＜ 0.001).Results There were 2 cases suffering from fat liquefaction of surgical incision and 1 case suffering from adhesive intestinal obstruction in patients undergoing transabdominal repair.In the median follow-up duration of 24 months (range 8-102 months)and 29 months (range 8-78 months),the successful rates of transvaginal repair and transabdominal repair were 75％ (24/32) and 93.5％ (29/31).Severe lower urinary tract symptoms occurred in one patient who had urine leakage after transabdomnal repair.The bladder volume of patients in transabdominal group recovered at postoperative 3-6 months.Conclusions In consideration of surgical invasion and fistula condition,transvaginal repair with layered closure and transabdominal repair with full thick vascular peritoneal interposition should be performed individually for complex VVF.Meanwhile,the surgeons need pay attention to other perioperative management.

Objective To explore influences of the fistula's location on the procedure and outcome of a transvaginal vesicovaginal (VVF) repair.Methods The medical data of patients undertaken transvaginal VVF repairs in Peking University First Hospital between Janurary 2009 and Auguest 2016 were retrospectively collected,including age,past history,causes of the fistula,disease course,past treatment,outcomes of the cystoscopy and imaging test and surgical information.The follow-ups were performed.Patients who had incomplete clinical data and lost to follow-up were not included.The present study included 68 VVF subjects with the median age of 46 years (range:24-64 years).The univariate analysis was performed to figure out potential risk factors for the VVF repair outcome.The duration and blood loss of VVF repairs were compared among the subjects with the fistulae located at bladder neck,trigone and supra-trigone region.Results There were 5,23 and 40 cases having VVFs located at bladder neck,trigone and supratrigone region respectively.The overall repair success rate was 88.2％ (60/68).According to results of the univariate analysis,subjects with more past repair times had significantly lower success rates.There were no significant differences in success rates of surgical repairs for VVFs located at bladder neck (80.0％,4/5),trigone (91.3％,21/23) and supra-trigone region (87.5％,35/40).And the location of VVFs had no significant association with the duration and blood loss during the VVF repair.Conclusions The location of VVFs had no influences on the procedure and outcomes of the transvaginal repairs.The VVF repair approach may not be determined based on the fistula's location alone.

Objective To analyze the clinical curative effect of arthroscopic acromioplasty treatment for subacromial impingement syndrome(SAIS). Methods A total of 52 patients who had SAIS were studied in our hospital by using the Neer score evaluation, the results of the pre-operative and post-operative scores were statistically analyzed. Results All the 52 cases were followed up, the follow-up ranged from 3 to 24 months with an average of 9 months. According to the Neer scoring system, 34 cases less than 70 points in the pre-operation were poor, 14 cases with 71-79 points were fair, 4 cases with 80-89 points were good. And 23 cases with 71-79 points in the post-operation were fair, 24 cases with 80-89 points were good,5 cases with more than 90 points were excellent. The Neer score was(55.25±19.00)before operation, and(81.13±6.28)after operation. There was a significantly statistical difference (t=-9.33, P<0.05). Conclusion The pain and activity of the patients were improved by the arthro scopic acromioplasty. And it has many advantages,such as faster post-operative recovery,low risk of complications and so on.

BACKGROUND:Studies have shown that thymosinβ4 can improve the anti-apoptotic ability of a variety of cells, but the reports describing the changes in the anti-apoptotic ability of bone mesenchymal stem cells modified with thymosinβ4 gene in the hypoxic environment are rare.
OBJECTIVE:To observe the change in the apoptotic rate of bone mesenchymal stem cells modified with thymosinβ4 gene in the hypoxic environment, and to explore whether thymosinβ4 affects the apoptosis of bone marrow mesenchymal stem cells via regulating the expression of Bax and Bcl-2.
METHODS:Bone marrow mesenchymal stem cells were transfected with the recombinant lentiviral vector over-expressing the thymosinβ4 gene, and then we observed the expression of thymosinβ4 using western blot assay. cells were divided into three groups:thymosinβ4 transfection group, control virus group, and untreated group. Al three groups were placed in a hypoxic environment. The apoptotic rate of bone marrow mesenchymal stem cells was evaluated by the flow cytometry assay. The expression of Bax and Bcl-2 protein was detected by western blot.
RESULTS AND CONCLUSION:Thymosinβ4 gene was expressed successful y in the bone marrow mesenchymal stem cells showed by the western blot. The apoptotic rate of bone marrow mesenchymal stem cells in the hypoxic environment was lower in the thymosinβ4 transfection group than the control virus group and untreated group;while there was no difference between the latter two groups. Western blot results showed that the expression of Bcl-2 protein was higher in the thymosinβ4 transfection group than the control virus group and untreated group, and the expression of Bax protein was lower in the thymosinβ4 transfection group than the control virus group and untreated group. No difference in the expression of Bax and Bcl-2 was found between the control virus group and untreated group. These findings indicate that thymosinβ4 overexpression can improve the anti-apoptotic ability of bone mesenchymal stem cells modified in the hypoxic environment, and its possible mechanism is through regulating the expression of Bax and Bcl-2 protein.

Objective To summarize the diagnosis and treatment of one case of combined heart liver transplantation. Methods On November 24, 2011, one case of combined heart-liver transplantation was performed on a patient with Ebstein's anomaly and tricuspid valve replacement after 5 years,complicated with congestive cirrhosis,liver failure dccompensation,preoperative heart failure Ⅲ degree and B grade of liver function Child-Pugh score. The operation was done with the graded cardiopulmonary bypass assisted mode:first creating the vena cava-aortic bypass to complete heart transplantation, second creating the femoral vein-ascending aorta bypass to complete liver transplantation,and third stopping and neutralizing.The aortic cross-clamping time was 54 min and the an hepatic phase was 38 min.The total time of three times of cardiopulmonary bypass was 199 min and the total time-consuming of operation was 517 min. The patient was given basiliximab +methylprednisolone for immune induction therapy, and tacrolimus + mycophenolate mofetil +prednisone solution for anti-rejection. After operation, liver protecting treatment, anti-infection therapy and nutrition support therapy were given.Results The recipient died of multiple organ failure after 78 days.The mechanical ventilation treatment duration for this recipient was 78 days and ECMO adjuvant therapy for postoperative hypoxemia time lasted 63 days.Conclusion The combined heart liver transplantation is an effective measures for treatment of heart and liver failure.

Objective To evaluate the clinical features and treatment of pelvi-ureteric junction obstruction (PUJO) in a duplex kidney. Methods From 1993 to 2010, 752 patients were diagnosed as PUJO in our hospital and 18 patients (2.4%) with PUJO in duplex kidneys. Three patients had obstruction in the complete duplicated systems and 15 in the incomplete duplicated systems. Five patients had obstruction of the upper moiety and 13 of the lower moiety. All of the 18 patients underwent B-ultrasonography, with 15 enhanced CT scan, 11 intravenous urography and 10 retrograde pyelography.All patients had serum creatinine test after admission and during the follow-up. Results Sixteen patients underwent operations and 2 patients were treated conservatively. Nine patients underwent pyeloplasty and 7 patients underwent heminephroureterectomy. Pathology shows derangement of the lamina muscularis at pelvi-ureteric junction and infiltration of inflammatory cells in mesenchymal. They were followed up from 6 months to 3 years with a mean of 24 months. The clinical symptoms of patients who underwent surgery were cured in all cases. B-ultrasound and IVU showed that hydronephrosis was obviously relieved and the levels of serum creatinine remained the same or decreased. The hydronephrosis and serum creatinine of patients who underwent conservative treatment remained stabilized. Conclusions PUJO in duplicated system is a rare condition. Careful preoperative evaluation is needed to reach the final diagnosis and retrograde pyelography has high specificity. Treatment should be individualized according to split and partial renal function.