On December 22,2021,the United States Food and Drug Administration approved the first main protease inhibitor,i.e.,oral antiviral nirmatrelvir(PF-07321332)/ritonavir(Paxlovid),for the treatment of early severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Nirmatrelvir inhibits SARS-CoV-2 infection,but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene expression.The chiral structure of nirmatrelvir plays a key role in its antiviral activity.Ritonavir boosts the efficacy of nirmatrelvir by inactivating cytochrome P450 3A4 expression and occupying the plasma protein binding sites.Multidrug resistance protein 1 inhibitors may increase the efficacy of nirmatrelvir.However,Paxlovid has many contraindications.Some patients treated with Paxlovid experience a second round of coronavirus disease 2019(COVID-19)symptoms soon after re-covery.Interestingly,the antiviral activity of nirmatrelvir metabolites,such as compounds 12-18,is similar to or higher than that of nirmatrelvir.Herein,we review the advances and challenges in using nirmatrelvir and its derivatives with the aim of providing knowledge for drug developers and physicians in the fight against COVID-19.

Exosomes are vesicles with a double globular membrane of lipids that can be secreted by a variety of cells, including stem cells. Exosomes have unique biological characteristics and irreplaceable powerful functions which play an important role in intercellular communication. The various cytokines, signal proteins, lipids and regulatory nucleic acids contained in stem cell exosomes can play a protective role against the injury of kidney, liver, heart, blood vessels and nerves. Stem cell exosomes delay the process of intervertebral disc degeneration by inhibiting the apoptosis of nucleus pulposus cells and increasing the synthesis of extracellular matrix, etc. The mechanism of its role is mainly through miRNA and related signaling pathways. Exosomes contain complex components. Although the mechanism of action of exosomes in intervertebral discs has been preliminarily explored, the components contained in exosomes are complex and the specific situation has not been fully understood, which still needs further study. In this review, the characteristics and functions of stem cell exosomes, extraction, identification and storage methods, the impacttovarious other tissues, as well as the effects on intervertebral discs and their mechanisms were elaborated in order to provide a basis for the study of intervertebral disc degenerative diseases.

Informatization plays an important role in the management of clinical diagnosis and treatment. However, due to the specialty of the discipline, the informatization construction of critical care medicine(CCM)is faced with such problems as the inefficient application of data, the low compliance of diagnosis and treatment operation, and the lack of intelligent quality control tools. The authors discussed the new mode of CCM information management based on data driven. By upgrading clinical information system, establishing single disease control system, introducing comprehensive intelligent analysis platform and building open remote platform, the bottleneck of CCM informatization was broken. The information collection and interaction in ICU was realized, the automatic monitoring and early warning of diagnosis and treatment process was realized, the operation of medical staff according to the guidelines was effectively improved, and the ability of diagnosis and treatment and management efficiency was improved.Furthermore, the homogenization of regional critical medical information could be promoted.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective To assess the efficacy and safety of febuxostat in the treatment of hypemricemia in renal transplant recipients.Methods A total of 124 renal transplant patients with hyperuricemia receiving febuxostat between June 2016 and July 2018 were retrospectively analyzed.Uric acid (UA),liver function and renal function parameters before and 3 months after treatment were compared.Adverse events,recipient and renal allograft survival were recorded throughout the follow-up period.Results Serum level of uric acid significantly decreased after 3-month treatment (P＜0.001).And 66.1％ of them achieved target UA level at Month 3 after dosing.Estimated glomerular filtration rate (eGFR) was maintained.No severe adverse event was observed.All recipient and renal grafts survived during the follow-up period.Conclusions Febuxostat is both effective and safe in the treatment of hyperuricemia in renal transplant.

Objective: To investigate the incidence of post-bronchiolitis recurrent wheezing and its risk factors in children. Methods: This study was conducted on patients with bronchiolitis admitted to the Department of Respiratory Disease, Children′s Hospital of Soochow University between November 2016 and March 2017.Nasopharyngeal secretions were taken from all patients and assessed for respiratory pathogens.After discharge, the patients were followed up every 3 months by outpatient visit or telephone call for 1 year. Results: Eighty-nine patients with bronchiolitis were enrolled in this study.Among those 89 patients, respiratory syncytial virus(RSV) infection accounted for 46.1%(41/89 cases), Mycoplasma pneumonia(MP) for 5.6%(5/89 cases), rhinovirus(RV) for 4.5%(4/89 cases), and human bocavirus(hBoV) for 2.2%(2/89 cases). Eighty-three patients were successfully followed up.At the 3, 6, 9, and 12 months of follow-up, the occurrence of wheezing episodes for only once happened in 20 cases(24.1%), 27 cases(32.5%), 35 cases (42.2%), and 38 cases(45.8%), respectively.At 12 months after initial bronchiolitis, the occurrence of wheezing episodes for only once happened in 21 cases(25.3%), 2 episodes of wheezing in 10 cases(12.0%), and 7 cases (8.4%) had more than 3 episodes of wheezing, and 6 cases lost follow-up.The proportion of eczema and milk-protein allergy in post-bronchiolitis recurrent wheezing group was significantly higher than that of the group with not post-bronchiolitis recurrent wheezing patients (χ²=6.219, 4.855, all P<0.05). Logistic regression analysis showed eczema was the independent risk factor for post-bronchiolitis recurrent wheezing(OR=0.189, 95%CI: 0.047-0.765). There were no significant difference in gender, age, premature birth, birth weight, feeding pa-tterns, family history of asthma, pet contact history, severity of disease, course of disease, total immunoglobulin E of serum and the species of virus infected between 2 groups(all P>0.05). Conclusions The incidence of recurrent wheezing among post-bronchiolitis patients is higher during one-year follow-up period.Eczema is the independent risk factor for post-bronchiolitis recurrent wheezing.The specific pathogens and severity of disease have no correlation with post-bronchiolitis wheezing.

Objective To explore the curative effect of colonoscopy combined with laparoscope in the treatment of colonic polyps.Methods The clinical data of 48 cases with colonic polyps were retrospectively analyzed.According to the operation pattern,the patients were divided into observation group(23 cases)and control group(25 cases).The observation group received colonoscopy combined with laparoscopy for radical surgery of colon polyps,the control group used the traditional open surgery to remove polyps.The operation time,bleeding volume, exhaust and defecation time,hospital days and cost as well as postoperative complications were observed.Results The two groups were successfully completed surgery.The operative time,bleeding volume of the observation group were (78.3 ±8.2)min and (1 3.1 ±4.5)mL respectively,which of the control group were (1 1 5.5 ±1 0.1 )min, (63.6 ±1 8.1 )mL,the differences between the two groups were statistically significant(t =1 3.93,1 3.01 ,all P <0.05).The anal exhaust time and defecation time of the observation group were (25.1 ±6.5)h and (42.5 ±7.6)h, which were significantly shorter than those of the control group[(36.6 ±8.1 )h,(82.3 ±1 1 .5)h],the differences were statistically significant(t =5.39,1 4.01 ,all P <0.05).The hospitalization time,hospital costs of the observation group were (5.5 ±0.6)d,(1 3 842.5 ±875.5)yuan,which of the control group were (8.2 ±1 .5)d,(1 8 992.5 ± 1 001 .5)yuan,the differences between the two groups were statistically significant(t =8.05,1 8.89,all P <0.05). Pulmonary infection in 1 case,anastomotic fistula in 2 cases,1 case of intestinal obstruction in the observation group, and in the control group,pulmonary infection occurred in 2 cases,2 cases of intestinal obstruction,the postoperative complications between the two groups had no statistically significant difference(P >0.05).Conclusion For simple colonoscopy treatment difficulties of colon polyps,colonoscopy,laparoscopy combined treatment is minimally invasive and can improve the safety,strictly control surgical indications,can give full play to the double mirror combined advantage.

Objective To study the safety and efficacy of damage control using percutaneous transhepatic biliary drainage (PTBD) in acute cholangitis of severe type (ACST) secondary to intrahepatic choledocholithiasis.Methods The clinical data of 8 patients who received PTBD after hospital admission followed by conventional surgery for ACST when their general condition improved were retrospectively studied.Results All patients received PTBD successfully and the amount of bile drained was 100-400 ml in the first day.The general condition of these 8 patients became better after 24 h and the total bilirubin decreased for about 25-100 mmol/L after 48 h.Three patients with a platelet count of less than 20 × 109/L showed an improved count to more than 50 × 109/L 72 h after PTBD.All patients were operated at different times after the PTBD:2 received T-tube drainage,3 T-tube drainage combined with left hepatectomy,and 3 choledochojejunostomy.Seven patients recovered uneventfully,but 1 developed hepatic failure with the total billurubin rose to more than 200 μmol/L.He was discharged home with the PTBD tube.During the waiting time of 7 days to 3 months before surgery,the tubes were kept patent and no mortality or morbidity such as bleeding,bile leakage,and peritonitis occurred.Conclusions PTBD was a safe and efficacious procedure for patients who were in a serious condition with ACST secondary to intrahepatic choledocholithiasis.It was more likely to be successful as it is minimally invasive and therefore well-tolerented.It reduced the biliary pressure,relieved the ongoing sepsis,and was a good preparatory procedure before any conventional surgery.

Objective To evaluate the efficacy and safety of CT-guided percutaneous celiac plexus block (NCPB) using 25 G controllable curved needle together with 22 G straight needle in treating refractory carcinomatous upper abdominal pain. Methods A total of 18 patients with advanced refractory carcinomatous upper abdominal pain were enrolled in this study. The carcinomatous upper abdominal pain failed to the three-step analgesic therapy. Guided by CT scan, percutaneous injection of ethanol with a 25 G controllable curved needle to destroy celiac plexus was carried out in all patients. According to WHO pain relief standards, the relieving degree of pain was evaluated before NCPB and 2 weeks, one, 2, 3 and 6 months after NCPB. The results were analyzed. Results The technical success rate was 100%. The short-term (within 2 weeks) efficacy rate was 88.8%and the complete remission rate was 38.8%. The long-term (over 3 months) efficacy rate was 50% and the complete remission rate was 20%. No severe complications occurred. Conclusion For refractory carcinomatous upper abdominal pain, CT-guided percutaneous celiac plexus block is a simple, safe and effective treatment.