Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

The Helicobacter pylori（Hp）infection rate in China has been at a high level.Although the infection rate of Hp in Chinese children has decreased with the development of social economy，drug-resistant strains are constantly emerging due to the wide application of antibiotics in children and so on.The eradication rate of previous Hp eradication programs shows to decline.The eradication treatment of Hp in children is facing great challenges.This article reviews the infection，drug resistance status and treatment progress of Hp in Chinese children，in order to provide the reference for the prevention and eradication treatment of Hp infection in children.

Objective:To investigate the technique and clinical effect of repairing 2 soft tissue defects on the same finger with a pedicled tandem flap of the first dorsal metatarsal artery and the second toe tibial artery.Methods:From March, 2018 to May, 2020, 8 patients, which were 5 males and 3 females, with 2 soft tissue defects in the same finger, were repaired with the first dorsal metatarsal artery flap in series with the second toe tibial flap. The causes of injury: 4 by crush, 2 by heavy object, and 2 by thermal press. There were 4 defects on index fingers, 2 on middle fingers and 2 on ring fingers. The defects ranged from 2.0 cm×2.5 cm to 2.5 cm×3.0 cm. All defects had exposed bone or tendon at varying degrees and 3 with phalanx fractures. Three patients underwent emergency surgery, the other 5 had sub-emergency surgery which were performed 3 to 5 days after the injury. The size of the flaps was 2.0 cm×2.5 cm to 3.0 cm×3.5 cm. The donor sites were sutured directly in 3 patients and 5 patients received skin grafting. The regular follow-up was performed. The survival of flaps, character, feeling and Total active motion(TAM), recovery of the foot donor area and complications were observed.Results:The operation time ranged from 2.0 to 5.5 hours, with an average of 3.5 hours. No vascular crisis occurred and all flaps survived after the surgery. All patients entered follow-up for 3-20 months, with an average of 8 months. The flaps had a good plump appearance, soft texture, good elasticity, and with a high similarity to the surrounding skin. The TPD of the flaps was 6-15 mm, with an average of 8 mm. The fingers had good flexion and extension functions. The incision in the donor site of the foot healed by first intention. The walking, running and jumping were normal without pain or discomfort.Conclusion:The first dorsal metatarsal artery-second toe tibial artery tandem flap has been used to repair 2 soft tissue defects in same finger. It simplifies the revascularisation of the flap together with exact surgical curative effect.

Objective: To explore the practical effect of pre-hospital prehabilitation strategy in pulmonary tumor patients. Methods: A total of 68 patients receiving thoracic surgery in Department of Pulmonary Oncology, Tianjin Medical University Cancer Institute & Hospital, during July 2018 to April 2019, were divided into pre-hospital prehabilitation group (n=34) and control group (n=34), according to the order of outpatient. Patients in control group received routine guidance before thoracic surgery, and those in pre-hospital prehabilitation group received a home-based preoperative intervention. The differences of 6-minute walking distance (6MWD), hospital anxiety and depression score (HADS), forced expiratory volume at the first second (FEV1), forced vital capacity (FVC), postoperative thoracic drainage and complications were compared between the two groups. Results: The values of 6MWD, FEV1 and FVC in the pre-hospital prehabilitation group were (611.08±47.13) m, (2.48±0.51) L and (3.43±0.48) L on one day preoperatively, respectively, while in the control group, the values were (520.26±57.33) m, (2.19±0.38) L and (3.17±0.58) L, respectively, with statistically significant differences, t=7.136, 2.659, 2.014, P<0.05. The values of 6MWD, FEV1 and FVC in the pre-hospital prehabilitation group were (540.27±85.73) m, (2.07±0.46) L and (2.98±0.67) L at 30 days postoperatively, respectively, while in the control group, the values were (488.86±75.04) m, (1.82±0.51) L and (2.42±0.58) L, respectively, with statistically significant differences, t=2.631, 2.122, 3.685, P<0.05. The thoracic drainage of pre-hospital prehabilitation group and control group were (162.35±43.08) ml and (191.42±69.11) ml, respectively, t=2.081, P<0.05. In addition, the occurrence rates of complications such as pulmonary infection, pulmonary atelectasis and arrhythmia were 0.0%(0/34), 2.9%(1/34), 0.0%(0/34) in the pre-hospital prehabilitation group, while those were 2.9%(1/34), 8.8%(3/34), 14.7%(5/34) in the control group, pre-hospital prehabilitation group had a significant reduction in the occurrence of arrhythmia (P<0.05). Conclusions The pre-hospital prehabilitation strategy significantly improve the perioperative functional status and prognosis of lung cancer patients, and reduce the occurrence of postoperative complications to a certain extent, which is worth of being further promoted clinically.

Objective To discuss the clinical effect of transplantation of slice nail bed flap of great toe with vascular anastomosis in repair of partial nail-bed and soft tissue defect at fingers.Methods From January,2015 to March,2018,16 cases (16 fingers) of partial nail-bed defect at fingers were repaired with transplantation of slice nail bed flap of great toe with vascular anastomosis.All cases were combined with palmar soft tissue defect at distal segment fingers.The area of nail bed defects were from 0.8 cr×0.5 cm to 1.2 cm×1.0 cm.The area of soft tissue defects were from 1.2 cm×1.0 cm to 2.5 cm×1.5 cm.The average time from injury to operation was 3.6 hours after injuries (ranging from 1 hour to 8 hours).The area of slice nail bed flap incised during operation were from 2.5 cm×1.2 cm to 3.2 cm×1.8 cm,and the donor site was sutured directly.All patients were followed-up regularly for nail appearance,function and donor healing.Among them,11 cases were followed-up by clinic,4 cases by WeChat,and telephone follow-up was performed in 1 case.Results The nail-bed flap after transplantation survived successfully.The followed-up time were from 6 to 18 months,the average time was 9 months.Longitudinal spine and rough appearance occurred in 1 case.Others were flat,smooth,complete attachment of nail body and nail bed.The flaps had good appearance,texture and elasticity at 6 months after surgery,and two-point discrimination was 6-12 mm(average,8 mm).The toenails at donor sites grew well.No walk-associated pain after long-term following-up.Six months after surgery,according to standard for efficacy evaluation of nail regeneration,12 cases were excellent,3 cases were good and 1 case was acceptable.Conclusion Transplantation of slice nail bed flap of great toe with vascular anastomosis in repair of partial nail-bed and soft tissue defect at fingers is one of the effective methods for repairing nail-bed defect at fingers.

Objective To establish S.O.L.V.E.nephrolithometry scoring system,and to evaluate value of S.O.L.V.E.scoring system for predicting the stone-free rate (SFR) of flexible ureteroscopy (FURS).Methods Five reproducible variables were included in S.O.L.V.E.scoring system,such as stone surface area (S),obstruction (O),length of calyces funnel (L),visible number of calyces (V) and essence of stone (E).Variables were measured based on preoperative non-contrast computed tomography of urography.Clinical data of 392 patients who underwent FURS for upper urinary tract stones in our department from January,2017 to Jnne,2018 were retrospectively analyzed.The total study population consisted of 258 male and 134 female patients.The mean age was (49.5 ± 12.6) years old,ranged from 15 to 85 years.There were 292 patients in stone-fiee group,including 197 male and 95 female patients.The average age was (49.2 ± 12.8) years old.37 patients had previous history of renal stone surgery.Median body mass index was 24.7 kg/m2 (18.1-29.0 kg/m2) and median value of preoperative serum creatinine was 72.5 μmol/L (48.9-84.8 μmol/L).The number of patients,whose stone located in the left side and right side were 155 and 137,respectively.The number of patients,whose stones located in ureter,renal pelvis,lower calyceal and non-lower calyceal were 19,16,87,170,respectively.There were 100 patients in non-stone free group,61 men and 39 women.The average age was (50.4 ± 12.0) years old.15 patients had previous history of renal stone surgery.Median body mass index was 25.0 kg/m2 (18.5-28.8 kg/m2) and median value of preoperative serum creatinine was 73.8 μmol/L (46.5-92.5 μnol/L).The number of patients,whose stone located in the left side and right side were 51 and 49,respectively.The number of patients,whose stones located in ureter,renal pelvis,lower calyceal and non-lower calyceal were 7,4,27,62,respectively.The correlation of S.O.L.V.E.scoring system and stone-free rate,postoperative hospital stay,surgical complications,operation time were analyzed.Receiver operating characteristic curves were drawn to detect predictive value of S.O.L.V.E.scoring system for SFR of FURS.Results All cases FURS were performed successfully and the SFR was 74.5％ (292/392).Among the variables of the S.O.L.V.E.scoring system in the stone-free group and the non-stone free group,item S were (82.6 ± 69.8) mm2 and (172.6±133.7)mm2,respectively.The item L were (12.7 ± 15.8) mm and (23.9 ± 15.3)mm,respectively.The item V were (0.6 ± 0.7) and (1.3 ± 0.8),respectively.The item E were (817.1 ± 285.5) HU and (902.4 ± 256.1) HU,respectively.The difference was statistically significant (P ＜ 0.01).The item O was (17.7 ± 10.9) mm and (19.3 ± 13.1) mm,respectively,no statistical significance was found (P =0.242).The mean score was 6.3 (ranging 4-11) in this c ohort.The patients were divided into low score (4-5) group,moderate score (6-8) group and high score (9-11) group due to S.O.L.V.E.scoring system,and the stone-free rates were 93.5％ (130/139),70.5％ (153/217) and 37.5％ (9/36),respectively (P ＜0.01).The operation time of low,moderate,andi high score group were (31.6 ± 10.9),(42.3 ± 18.3),and (58.0 ± 19.2) min,respectively.Additionally,the score was correlated with the operation time(P ＜0.01),but not with postoperative hospital stay (P =0.133),intraoperative bleeding (P =0.185) and postoperative infectious fever (P =0.839).In logistic regression model analysis,the stone surface area,length of calyces funnel,number of involved calyces were significantly correlated with SFR (P ＜ 0.01).The obstruction degree and essence of stone were not associated with SFR (P ＞ 0.05).The area under receiver operating characteristic curve of S.O.L.V.E.score was 0.782,higher than that of each variable in S.O.L.V.E.scoring system(S,O,L,V,E were 0.738,0.535,0.698,0.735,0.593,respectively).Conclusions The stone surface area,length of calyces funnel,number of involved calyces were significantly correlated with SFR.The S.O.L.V.E.nephrolithometry scoring system can predict SFR after FURS accurately,and provide assistance for making clinical decisions.

Objective To explore the clinical effect of using hallux-nail flap with the distal part of phalanx combined with iliac bone for reconstruction of thumb with Ⅲ degree defect.Methods From June,2011 to June,2016,7 patients with thumb Ⅲ degree defect were treated with the hallux-nail flaps with distal phalanx combined with iliac bone to reconstruct thumbs.According to the thumb defect indexing method reported by Cheng Guoliang,the type 1 of thumb Ⅲ degree defect was 4 cases,and the type 2 of Ⅲ degree defect was 3 cases.The donor site was covered with skin grafting in 1 case,free superficial iliac artery graft in 5 cases and free peroneal artery perforator flap in 1 case.All patients kept the number and length of donor toes.Regular follow-up was performed after operation to observe the function,shape,feeling of finger reconstruction,the survival condition of flaps or skin graft in donor site,etc.It was also observed if the pain by walking actually exists in the long-term effect.Results All of the reconstructed thumbs survived.One patient suffered the necrotic in the donor site repaired by superficial iliac artery flap,which was successfully covered with the skin graft.All patients were followed-up from 3 months to 18 months (mean,8 months).The reconstructed thumb with smooth nail had fine textile and good elasticity,good flexion and extension function of the palm,fingers and the metacarpophalangeal joint.The donor sites recovered with fine texture,and there were no difficulties in walking and running and no complaint about the pain and discomfort.According to the Trial Criteria of Upper Limb Functional Evaluation of Chinese Medical Association Hand Surgery Society,5 cases resulted in excellent,and 2 cases resulted in good.Conclusion The hallux-nail flap with the distal phalanx combined with iliac bone is an excellent option to reconstruct thumb with Ⅲ degree defect with the outcome of good function and appearance.The trauma of the donor site is small and the number and length of the toes are remained.The clinical effect is good.

Objective To discuss the clinical effect of partial nail-bed flap at second toe with blood-vessel anastomosed in repair of different types of nail-bed defects at finger.Methods From July,2010 to July,2015,25 cases of partial nail-bed flap at second toe with blood-vessel anastomosed were treated,including 14 males and 11 females,with an age range from 18 to 45 years old (average 25 years old).Eleven cases at index finger,6 cases at middle finger,5 cases at ring finger and 3 cases at little finger.According to the classification of nail bed defect site,9 cases at lateral,5 cases at nail root and 11 cases at distal.All cases were combined skin and soft tissue defect.The area of defects were from 1.1 cm × 2.0 cm to 2.5 cm × 3.2 cm.The time from injury to admission were from 1 hour and 12 minutes to 3 hours and 12 minutes,the average time was 2.1 hours.The area of incised nail flap during operation were from 1.2 cm × 2.2 cm to 2.6 cm × 3.5 cm.The donor site was sutured directly or repaired with free skin graft.The toe length in all cases were retained.The nail shape,nail gloss,fine function of finger such as pinch,grip,grasp and restoration of the donor toes were compared in the follow-up.All patients were followed-up at regllar intervals.Results The nail-bed flap after transplantation and skin graft at donor site survived successfully,and primary healing of the wounds occured in all cases.The follow-up time were from 6 to 26 months(average 9 months).Longitudinal spine or transverse groove occurred in 3 cases at the nail-bed boundary between toe and finger,nail thickened and distal tilted occurred in 1 case,flat,smooth,no deformity nail and glossy deck occurred in others.The flap had good appearance,texture and elasticity.Two-point discrimination was 5-9 mm,averageal of 6 mm.The donor toe had no shortening and no pain after long-term following.According to effectiveness standard for fingernail regeneration:19 cases were excellent and 6 cases were good.Conclusion Partial nail-bed flap at second toe wih bloodvessel anastomosed in repairing nail-bed defects at finger,nail appearance is realistic and function recovered well postoperatively.

Objective To study the impact of aging on the capability of lung stem cell steady-state maintaining and bronchial epithelial cells regeneration and differentiation during the repair of lung epithelial cells after naphthalene induced bronchial epithelialium injury.Methods The proportion of lung stem cells in mice after naphthalene treatment was analyzed by immunohistochemistry and FACS.The repair efficiency of lung epithelial cell in young and old mice was examined by immunohistochemistry staining and FACS.Results The data suggested that aging didn ’ t change the proportion of lung stem cells ( including the distal lung epithelial stem cells/progenitor cells and lung mesenchymal stem cells/progenitor cells) under normal physiological conditions.After naphthalene injury, more serious injury and decreased repairing capacity was observed in old group.Lung progenitor cells /total lung cells decreased during the repair process of lung bronchial epithelialium ( clara cell) injury.The ratio of regenerated cell to lung progenitor and stem cells were also significantly decreased in old group.Conclusion The regenerated capability of lung stem cells after lung bronchial epithelialium injury decreased with aging.This might be the reason of more incidence of lung injury and worse therapeutic results in the elder in clinic.

A novel recombinant Bacille Calmette-Guerin (rBCG) vaccine co-expressed Eimeria tenella rhomboid and cytokine chicken IL-2 (chIL-2) was constructed, and its efficacy against E. tenella challenge was observed. The rhomboid gene of E. tenella and chIL-2 gene were subcloned into integrative expression vector pMV361, producing vaccines rBCG pMV361-rho and pMV361-rho-IL2. Animal experiment via intranasal and subcutaneous route in chickens was carried out to evaluate the immune efficacy of the vaccines. The results indicated that these rBCG vaccines could obviously alleviate cacal lesions and oocyst output. Intranasal immunization with pMV361-rho and pMV361-rho-IL2 elicited better protective immunity against E. tenella than subcutaneous immunization. Splenocytes from chickens immunized with either rBCG pMV361-rho and pMV361-rho-IL2 had increased CD4+ and CD8+ cell production. Our data indicate recombinant BCG is able to impart partial protection against E. tenella challenge and co-expression of cytokine with antigen was an effective strategy to improve vaccine immunity.
Adjuvants, Immunologic/genetics/*metabolism ; Administration, Intranasal ; Animals ; Antigens, Protozoan/genetics/*immunology ; BCG Vaccine/administration & dosage/*genetics ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Chickens ; Coccidiosis/*prevention & control ; Disease Models, Animal ; Drug Carriers/administration & dosage ; Eimeria tenella/genetics/*immunology ; Genetic Vectors ; Injections, Subcutaneous ; Interleukin-2/genetics/*metabolism ; Protozoan Vaccines/administration & dosage/genetics/*immunology ; Spleen/immunology ; Vaccines, Synthetic/administration & dosage/genetics/immunology