Objective To compare the clinical efficacy and safety differences between the triple immunosuppressive regimen of mizoribine (MZR) or mycophenolate mofetil (MMF) combined with tacrolimus (Tac) and glucocorticoids of kidney transplant recipients in one year after transplantation. Methods A single-center retrospective cohort study design was adopted. The clinical data of 156 patients who underwent the first allogeneic kidney transplantation at the Third Hospital of Peking University from January 2022 to December 2024 were included. The patients were divided into the MZR group (78 cases) and the MMF group (78 cases) based on the initial immunosuppressive regimen after transplantation. The baseline data, medication use in one year after transplantation, blood routine indicators, adverse events and clinical outcomes were compared between the two groups. For the repeated-measurement longitudinal data, repeated-measurement analysis of variance was used to evaluate the main effects of the groups, time and their interaction effects. Results At the primary efficacy endpoint, there were no statistically significant differences in the one-year survival rate, graft survival rate and incidence of acute rejection between the two groups (all P > 0.05). In terms of medication patterns and laboratory test indicators, there were significant time main effects and "time × group" interaction effects for Tac dosage (all P < 0.05). The Tac dosage in the MZR group was lower than that in the MMF group from 2 to 3 months after transplantation, and it was higher in the MZR group than in the MMF group from 7 to 12 months and one year after transplantation. White blood cell count in the MZR group was higher at one month after transplantation, and the platelet count was higher one year after transplantation (all P < 0.05). In terms of infection, the incidence of novel coronavirus and Pneumocystis jirovecii pneumonia infections in the MZR group was lower (all P < 0.05). In terms of metabolic indicators, the post-transplantation uric acid level was better in the MZR group than in the MMF group, but the total cholesterol level was higher one year after transplantation (all P < 0.05). In terms of liver function, there was a brief and mild increase in transaminase in the early stage after transplantation in the MZR group. Conclusions During the one-year follow-up after transplantation, both the MZR and MMF regimens demonstrate comparable immunosuppressive efficacy and overall safety in Chinese kidney transplant recipients. The MZR regimen shows clear advantages in reducing specific infection risks, alleviating bone marrow suppression and improving uric acid metabolism, but its potential impact on blood lipids needs to be monitored. Therefore, the MZR regimen may be an effective and safe alternative immunosuppressive option for kidney transplant recipients, especially those with high infection risk, poor hematological tolerance, or comorbid hyperuricemia.

Objective:To review and summarize the experience of robot-assisted laparoscopic trans-plant nephrectomy,share the surgical steps and technical key points,and provide a reference for clinical practice.Methods:A retrospective analysis was conducted on the perioperative data of 5 patients who underwent robot-assisted laparoscopic donor nephrectomy at Peking University Third Hospital from August 2023 to December 2024.The surgical steps and key points were summarized.The continuous variables were described by medians(ranges).Results:A total of 5 patients were included in the analysis,of whom 2 were male and 3 were female.The median age of the patients was 37(31-68)years.The me-dian time from kidney transplantation to donor nephrectomy was 10(3-22)years.The indications for donor nephrectomy included recurrent hematuria,abdominal pain,malignant tumor of the transplanted kidney,and recurrent infection with hydronephrosis of the transplanted kidney.The excised transplanted kidneys from all the 5 patients had a single renal artery and a single renal vein.The median operation time was 212(145-351)min,the median blood loss was 300(20-500)mL,and the median post-operative hospital stay was 7(4-25)days.Only 1 patient experienced intraoperative complications,who experienced an external iliac artery injury during the operation and underwent suture repair.No pa-tient died during the perioperative period.Postoperative pathological results showed that 3 patients had end-stage non-functional kidneys,1 patient had BK virus-associated urothelial carcinoma,and 1 patient had chronic pyelonephritis with renal parenchymal atrophy.Conclusion:Robot-assisted laparoscopic transplant nephrectomy as a new surgical approach is feasible and safe.Compared with traditional open transplant nephrectomy,its advantage lies in the ability to directly observe and prioritize the management of the renal pedicle of the transplanted kidney,while completely freeing and removing the transplanted kidney outside the renal capsule.With the continuous accumulation of experience,this surgical technique is expected to become a powerful alternative to traditional open transplant nephrectomy.

Objective:To review and summarize the experience of robot-assisted laparoscopic trans-plant nephrectomy,share the surgical steps and technical key points,and provide a reference for clinical practice.Methods:A retrospective analysis was conducted on the perioperative data of 5 patients who underwent robot-assisted laparoscopic donor nephrectomy at Peking University Third Hospital from August 2023 to December 2024.The surgical steps and key points were summarized.The continuous variables were described by medians(ranges).Results:A total of 5 patients were included in the analysis,of whom 2 were male and 3 were female.The median age of the patients was 37(31-68)years.The me-dian time from kidney transplantation to donor nephrectomy was 10(3-22)years.The indications for donor nephrectomy included recurrent hematuria,abdominal pain,malignant tumor of the transplanted kidney,and recurrent infection with hydronephrosis of the transplanted kidney.The excised transplanted kidneys from all the 5 patients had a single renal artery and a single renal vein.The median operation time was 212(145-351)min,the median blood loss was 300(20-500)mL,and the median post-operative hospital stay was 7(4-25)days.Only 1 patient experienced intraoperative complications,who experienced an external iliac artery injury during the operation and underwent suture repair.No pa-tient died during the perioperative period.Postoperative pathological results showed that 3 patients had end-stage non-functional kidneys,1 patient had BK virus-associated urothelial carcinoma,and 1 patient had chronic pyelonephritis with renal parenchymal atrophy.Conclusion:Robot-assisted laparoscopic transplant nephrectomy as a new surgical approach is feasible and safe.Compared with traditional open transplant nephrectomy,its advantage lies in the ability to directly observe and prioritize the management of the renal pedicle of the transplanted kidney,while completely freeing and removing the transplanted kidney outside the renal capsule.With the continuous accumulation of experience,this surgical technique is expected to become a powerful alternative to traditional open transplant nephrectomy.

Objective:To systematically evaluate the prevalence of norovirus causing sporadic acute gastroenteritis in China.Methods:Relevant articles on acute gastroenteritis caused by norovirus in China published between January 2010 and October 2023 were retrieved from Wanfang, CNKI and PubMed database. The articles met inclusion and exclusion criteria were enrolled in this study. Excel software and SPSS20.0 software were used for statistical analysis. The epidemiological features of sporadic cases of acute gastroenteritis caused by norovirus in China were summarized using descriptive statistical analysis.Results:A total of 500 articles were included in this study, involving 784 486 cases of acute gastroenteritis and 670 292 samples in 32 provinces and regions. Norovirus GⅡ was the predominant genogroup causing acute gastroenteritis in China in recent years, but there were significant differences in the distribution of genotypes and epidemic strains at different times. GⅡ.4 was the predominant genotype in each year, and GⅡ.4/2006b and GⅡ.4 /Sydney_2012 were the main epidemic strains. Norovirus-related diarrhea occurred throughout the year, especially between the months of October and December. The incidence of norovirus infection was high in children under five years old and varied in different regions.Conclusions:Norovirus GⅡ was the predominant genogroup causing norovirus-related sporadic acute gastroenteritis in China, but there was an obvious genetic evolutionary trend in the epidemic strains. Factors such as epidemic strains, season and geographical region should be considered when making strategies for the prevention and control of norovirus-related diarrhea and developing vaccines.

Since the 21st century, minimally invasive technique has become a main development direction of surgery, which has been widely applied in all branches of surgery. In the field of kidney transplantation, minimally invasive technique has been mainly applied in the procurement of living donor kidney, kidney transplantation and the management of complications after kidney transplantation. It not only increases the resource of donor kidney, but also reduces the incidence of postoperative complications and enhances the quality of life of the recipients. The application of minimally invasive technique has become one of the research hot spots in the field of kidney transplantation. In this article, research progresses on the application of minimally invasive technique in the procurement of living donor kidney, kidney transplantation and management of complications after kidney transplantation were reviewed, aiming to provide reference for increasing the resource of donor kidney, enhancing the success rate of kidney transplantation and improving clinical prognosis of kidney transplant recipients, thereby promoting the development of minimally invasive technique in surgery.

Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, the mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, a drug that is commonly the first medication prescribed for type 2 diabetes, can induce CMA. We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA, Hsc70, and its activation. Notably, we find that amyloid-beta precursor protein (APP) is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner. The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity. Importantly, we find that in the APP/PS1 mouse model of Alzheimer's disease (AD), activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβ plaque levels and reverses the molecular and behavioral AD phenotypes. Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases, such as AD, where such therapeutic intervention could be beneficial.

Objective: To detect norovirus (NoV) GⅠ.1- and GⅡ.4-specific IgG, IgA and histo-blood group antigen (HBGA)-blocking antibodies in healthy populations of all age groups in China for better understanding the epidemiological features of norovirus in China from a serological point of view and providing basic data for vaccine development and clinical trial design. Methods: Indirect ELISA and HBGA-blocking assay were used to detect NoV-specific IgG, IgA and HBGA-blocking antibodies in serum samples collected from healthy natural populations (n=839, aged from six months to 88 years old) in Guangzhou, Fuyang and Yantai. The results were statistically analyzed. Results: The total positive rates of NoV GⅠ.1- and GⅡ.4-specific IgG antibodies were 91.9% and 93.0%. The positive rates of GⅠ.1- and GⅡ.4-specific IgA antibodies were 48.6% and 75.6%, and the titers of HBGA-blocking antibodies to GⅠ.1 and GⅡ.4 norovirus were 5.04 (95%CI: 4.63-5.49) and 18.15 (95%CI: 16.11-20.44). The positive rates of IgG and IgA antibodies generally showed an increasing trend with age. The positive rates of GⅠ.1- and GⅡ.4-specific IgG antibodies ranged from 79.2% to 100.0% and 76.7% to 100.0% in different age groups. They were 81.7% and 85.0% in the age group of 0.5-<1 year, 79.2% and 76.7% in the age group of 1-<2 years, and 98.1% and 96.3% in the age group of 12-<18 years, and maintained at 96% and 98% in the older age groups. The positive rates of GⅠ.1-specific IgA antibody ranged from 11.7% to 93.8% in different age groups and rapidly increased with age. It was 11.7% in the age group of 0.5-<1 year, and reached 93.3% in people aged 45-<60 years and 93.8% in people aged ≥60 years. The positive rates of GⅡ.4-specific IgA antibody ranged from 50.8% to 88.8% in different age groups with 50.8% in people aged 0.5-<1 year, and 86.7%-90.7% in people aged 12-<18 years and older. The titer of GⅠ.1 HBGA-blocking antibody generally increased with age. The antibody titer in populations aged 0.5-<12 years old was lower than that in those aged 18 years and above (GMT: 2.98-4.07 vs 8.21-11.62, P<0.001), and the titer in people of 12-<18 years old was lower than that in those of 45 years old and above (GMT: 5.21 vs 11.03-11.62, P<0.05). No obvious change with age was observed in the titer of GⅡ.4 HBGA-blocking antibody excepting the significant difference between populations of 2-<5 and 22-<45 years old (GMT: 26.73 vs 11.87, P<0.01). Conclusions This study revealed the characteristics of serum NoV GⅠ.1- and GⅡ.4-specific IgG, IgA and HBGA blocking antibodies in populations of different age groups in central and eastern China through analyzing their positive rates and titers and provided preliminary seroepidemiological data for the development of NoV vaccines in China.

Norovirus is one of the leading causes of acute non-bacterial gastroenteritis. Emergence of new genotypes due to frequent genetic recombination and antigenic drift increases the prevalence of noro-virus infection worldwide. Norovirus infection has become a global public health concern. This review fo-cused on disease burden, vaccine research, cell culture and animal models regarding norovirus infection.

Objective To evaluate the immune effects of virus-like particles ( VLPs) assembled from the capsid protein VP1 of a recombinant norovirus ( NoV) GⅡ. 17 genotype. Methods The recombi-nant NoV GⅡ. 17 VP1 VLPs were purified, and then tested by SDS-PAGE and Western blot to analyze the purity. The size, morphology and diameter distribution of the recombinant VLPs were detected by transmis-sion electron microscopy ( TEM) and dynamic light scattering ( DLS) analyzer. The recombinant VP1 VLPs adsorbed by aluminium adjuvant were used to immunize BALB/c mice. Serum samples were collected after immunization. Specific antibody level and neutralizing antibody activity were evaluated with enzyme linked immunosorbent assay ( ELISA) and histo-blood group antigen ( HBGA)-VLP blocking test. Cross-reactivity of serum samples with GⅠ. 1 and GⅡ. 4 VP1 VLPs were detected. Moreover, cross-protection against GⅠ. 1 and GⅡ. 4 VP1 VLPs was analyzed. Results The purity of the recombinant NoV GⅡ. 17 VP1 VLP was greater than 90％ and specific bands were detected by Western blot. TEM images and DLS experiments showed that VLPs were 30-50 nm in size with good morphology and uniformity, indicating that the recombi-nant VLPs were similar to the wildtype virus. High titers of specific antibodies were detected in serum sam-ples of the immunized mice. A certain degree of cross-reactions between serum samples and VP1 VLPs of NoV GⅠ. 1 and GⅡ. 4 were observed, but no cross-protection was detected. Conclusion The recombinant GⅡ. 17 VP1 VLPs in combination with aluminum adjuvant can induce higher titers of HBGA blocking anti-bodies in mice, suggesting that it could be used as a candidate target antigen for norovirus vaccine.