Objective To evaluate the effect of irregular follow-up during normalized prevention and control of novel coronavirus pneumonia (COVID-19) epidemic on BK virus (BKV) reactivation and clinical prognosis of kidney transplant recipients. Methods Clinical data of 363 kidney transplant recipients were retrospectively analyzed, and they were divided into the pre-epidemic follow-up group and during-epidemic follow-up group according to the follow-up time. All patients were followed up for 1 year. The follow-up interval was compared between two groups. The infection of BKV and the correlation between the infection process of BKV and renal graft function were analyzed in two groups. Results A total of 1 790 preson-times were followed up before COVID-19 epidemic and 2 680 during COVID-19 epidemic. Compared with the during-epidemic follow-up group, the follow-up intervals within 3, 3-6 and 7-12 months after kidney transplantation were shorter in the pre-epidemic follow-up group, and the differences were statistically significant (all P<0.05). Within 1 year after kidney transplantation, 35 cases（32%） were diagnosed with BKV viruria, 3 cases（3%） of BKV viremia and 1 case（1%） of BKV-associated nephropathy (BKVAN) in the pre-epidemic follow-up group, and 53（25%）, 3（1%） and 1（1%） in the during-epidemic follow-up group, with no statistical significance (all P>0.05). In the pre-epidemic follow-up group, the time for the initial diagnosis of BKV viruria was longer and the viral load of the first urinary BKV reactivation was smaller than those in the during-epidemic follow-up group, with statistical significance (both P<0.05). The load of the first urinary BKV reactivation was positively correlated with the peak load of urinary BKV, and the differences between the baseline and serum creatinine levels at 1 and 3 months after BKV reactivation (all P<0.05). Conclusions Irregular follow-up after kidney transplantation may lead to early BKV reactivation and higher detection value of the first viral load of urinary BKV, delay diagnosis and interventions, and lead to poor prognosis. It is urgent to establish a remote follow-up system to meet the follow-up requirements of kidney transplant recipients when public health incidents occur.

Objective To explore prenatal ultrasonic characteristics of fetal Currarino syndrome(CS)and methods for prenatal diagnosis of CS.Methods Two fetuses with CS confirmed by genetic examination were retrospectively analyzed,while 6 CS fetuses with complete prenatal ultrasonic data in literature were reviewed.Prenatal ultrasonic characteristics of CS fetuses and the method for prenatal diagnosis of CS were discussed.Results Among 8 CS fetuses diagnosed with prenatal ultrasound,4 were female singletons with a clear family history of CS,and MNX1 gene mutation was found in 1 fetus.The other 4 fetuses were 2 pairs of male monochorionic twins,all with MNX1 gene mutation.Among 8 CS fetuses,complete triad(sacral agenesis abnormalities,anorectal malformation and presacral mass)were displayed only in 2 fetuses,while all 8 had sacral agenesis abnormalities and 6(6/8,75.00％)were detected with prenatal ultrasound,6 had low location of conus medullaris and 2(2/6,33.33％)detected with prenatal ultrasound.Conclusion Prenatal ultrasound was the first choice for non-invasive diagnosis of fetal CS.When one of sacral agenesis abnormalities,anorectal malformation and presacral mass was found with prenatal ultrasound,the possibility of CS should be considered,and fetal MRI,genetic examination and prenatal genetic counselling should be recommended if necessary.

Objective:To study the clinical features, treatment and prognosis of multiple myeloma (MM)complicated with extramedullary disease (EMD).Methods:A total of 65 patiens admitted to the Characteristic Medical Center and Tianjing First Central Hospital from January 2014 to May 2020 were analyzed retrospectively as the study subjects. The age ranged from 22 to 79 years, with a median age of 56(22,79) years, and the ratio of female to male was 27/38. They were respectively treated by chemotherapy, radiotherapy or autologous hematopoietic stem cell transplantation (AHSCT). Fluorescence in situ hybridization (FISH) was used in all 65 patients to detect t(4;14), t(14;16), 1q21, del(17p). The measurement data of non-normal distribution were expressed in M (Q1,Q3), and the survival curve was constructed by Kaplan-Meier method.Result:The increase of β2- microglobulin and lactate dehydrogenase, multiple osteolytic lesions were found in all patients. The most common rate of chromosomal abnormalities were10.8% for t(4;14), 16.9% for t(14;16), 18.5% for 1q21, 21.5% for del(17p). Both 1q21 and del(17p) were co-existed in 7.7% of patients. The effective rate of 65 patients treated with V-DRPACE regimen was 89.2%(58/65). Thirty-two patients who were in partial remission were treated with radiotherapy. The complete remission rate of radiotherapy was 18.8%(6/32). Twenty patients eligible for transplantation underwent AHSCT and 13 patients achieved complete remission. At the end of follow-up, the median overall survival(OS) of 65 patients was 44.8 months, and progression-free survival (PFS) was11 months.Conclusion:MM with EMD usually involve multiple sites, prone to multiple osteolytic lesions, increased β2- microglobulin and lactate dehydrogenase. The rate of cytogenetic abnormalities in such patients is significantly increased. The V-DRPACE regimen is effective in treating MM patients with extramedullary lesions and can benefit from AHSCT.

Objective To investigate the mechanism of action of Huzhang Qingmai decoction (HZQMY) on the improvement of cognitive function in mice with chronic cerebral ischemia from the perspective of intestinal flora. Methods A mouse model of chronic cerebral ischemia was established by placing microcoils around the bilateral common carotid arteries to induce bilateral carotid artery stenosis (BCAS). After 12 weeks of intragastric administration, the cognitive function of the mice was measured by the Morris water maze; the myelin damage was analyzed by LFB staining; The contents of the cecum of the mice in each group were extracted and analyzed by 16S rRNA sequencing. Results The results of the water maze experiment showed that the mice in the HZQMY group had a significantly shorter escape latency, increased the number of crossings platform and the percentage of target quadrants. LFB staining showed that the white matter damage in the model group was severe; the white matter damage in the HZQMY group was milder. The results of 16S rRNA sequencing showed that compared with the model group, the abundance of Verrucomicrobiota, Akkermansia, and ErysiPelatoclostridium capsulatum in the intestinal flora in HZQMY group was significantly reduced (P<0.05), while the abundances of Eubacterium_xylanoPhilum and Allobaculum were significantly increased (P<0.05). Conclusion The protective effect of HZQMY, which has the effect of improving cognitive function in mice with chronic cerebral ischemia, may be related to the regulation of intestinal flora in mice with chronic cerebral ischemia.

Acute Disease ; Allografts ; Humans ; Kidney ; Kidney Transplantation ; Nephritis ; Pyelonephritis ; Transplantation, Homologous

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*

Objective To explore the mechanism of motherwort in the treatment of nerve injury. Methods The active components of motherwort were obtained by searching TCMSP and BATMAN-TCM databases. The action targets of candidate compounds were collected and predicted from TCMSP and SwissTargetPrediction (STP) databases. The target genes corresponding to the active components of motherwort were obtained by using the standardized database of disease targets (Uniprot). The potential targets of motherwort in the treatment of nerve injury were obtained by mapping the disease genes of nerve injury with the three databases of Genecards, DisGenet and OMIM. The network topology analysis software Cytoscape 3.6.0 was used to construct the action target network of motherwort active components. The protein interaction platform database (STRING) was used to construct the interaction relationship between action targets. The target protein interaction (PPI) network was constructed by introducing Cytoscape 3.6.0 software. Through STRING database, GO enrichment analysis and KEGG pathway enrichment analysis were carried out to analyze the target points of motherwort in the treatment of nerve injury. Results 19 active components were screened from motherwort, involving 654 action targets, including 426 action targets related to nerve injury and 6 key targets. These target genes were mainly involved in biological regulation, oxidative stress response and cell communication and other biological processes. Molecular functions were mainly related to protein binding, ion binding and catalytic reduction. They were enriched outside the cell membrane. Its mechanism was related to signal pathways such as MAPK, Toll-like receptor, PI3K-Akt, TNF, IL-17, and apoptosis. Conclusion The active components of motherwort may play a protective role on nerve injury through anti-inflammation, anti-apoptosis and promoting cell growth.

Objective:To investigate the prognosis of robotic pancreatoduodenectomy after the learning curve and open pancreatoduodenectomy for pancreatic cancer.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 396 patients who underwent curative pancreatoduodenectomy for pancreatic duct adenocar-cinoma in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from January 2017 to December 2018 were collected. There were 244 males and 152 females, aged 64(range, 36?92)years. Of 396 patients, 86 cases undergoing robotic pancreatoduodenectomy were divided into robotic group, 310 cases undergoing open pancreatoduodenectomy were divided into open group. Observa-tion indicators: (1) propensity score matching and comparison of general data between the two groups after matching; (2) follow-up and survival analysis. Follow-up was conducted by telephone interview or outpatient examinations including tumor markers and abdominal imaging examina-tions to detect survival of patients up to March 2022. Overall survival was defined as the time from the surgery date to death or the last follow-up. Disease-free survival was defined as the time from the surgery date to tumor recurrence or the last follow-up. The propensity score matching was conducted by 1∶1 matching using the nearest neighbor method. Normality of measurement data was examined using the Shapiro-Wilk test. Measurement data with skewed distribution were described as M(range), and comparison between groups was analyzed using the Mann-Whitney rank-sum test. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-Rank test was used for survival analysis. An intent-to-treat analysis was performed in this study, patients who were converted to laparotomy from robotic surgery were still divided into the robotic group. Results:(1) Propensity score matching and comparison of general data between the two groups after matching: 164 of 396 patients had successful matching, including 82 cases in robotic group and open group, respectively. Before propensity score matching, the body mass index, cases in stage T1, T2, T3, T4, cases in N0, N1, N2 were 23.4(range, 21.4?25.3)kg/m 2,24, 41, 10, 11, 52, 27, 7 for the robotic group, versus 22.4(range,20.3?23.9)kg/m 2,57, 144, 22, 87, 131, 132, 47 for the open group, showing significant differences in the above indicators between the two groups ( Z=3.01, 2.63, 3.03, P<0.05). After propensity score matching, cases of males, age, body mass index, cases with American Society of Anesthesiologists (ASA) score as 1, 2, 3, CA19-9, cases with preoperative biliary drainage, cases with portal vein resection, cases with pancreatic resection margin <1 mm, cases in stage T1, T2, T3, T4, cases in stage N0, N1, N2, cases with nerve invasion, cases with tumor differentiation as high-medium differentiation, medium-low differentiation, low differentiation, cases with adjuvant chemotherapy were 51, 65(range, 59?69)years, 23.0(range, 21.0?25.2)kg/m 2, 32, 41, 9, 160.4(range, 46.7?377.2)U/mL, 21, 9, 8, 21, 40, 10, 11, 48, 27, 7, 76, 26, 47, 9, 53 for the robotic group, versus 58, 65(range, 58?69)years, 23.3(range, 21.4?25.3)kg/m 2, 35, 39, 8, 172.0(range, 69.7?402.9)U/mL, 26, 9, 10, 24, 40, 7, 11, 49, 28, 5, 76, 22, 49, 11, 57 for the open group, showing no significant difference in the above indicators between the two groups ( χ2=1.34, Z=0.18, 0.34, 0.49, 0.51, χ2=0.75, 0.00,0.25, Z=0.59, 0.27, χ2=0.00, Z=0.76, χ2=0.44, P>0.05). (2) Follow-up and survival analysis: after propensity score matching, 164 patients were followed up for 54(range, 1?67)months. The follow-up time of patients was 55(range, 51?59)months for the robotic group, versus 54(range, 50?58)months for the open group, respectively, showing no significant difference between the two groups ( Z=0.48, P>0.05). During the follow-up, the 1-year overall survival rate, 3-year overall survival rate, the median survival time, 1-year disease-free survival rate, 3-year disease-free survival rate, the median disease-free survival time, tumor recurrence rate, cases with recurrence pattern as local recurrence, liver recurrence, other distant recurrence, local and distant recurrence were 81.7%, 39.0%, 27 months(95% confidence interval as 19?33 months), 61.0%, 34.2%, 15 months(95% confidence interval as 12?18 months), 54.9%(45/82), 12, 16, 9, 8 for the robotic group. The above indicators were 79.3%, 36.0%, 24 months(95% confidence interval as 19?31 months), 59.8%, 27.5%, 15 months(95% confidence interval as 10?20 months), 58.5% (48/82), 10, 22, 6, 10 for the open group. There was no significant difference in overall survival or disease-free survival between the two groups ( χ2=0.39, 0.47, P>0.05). There was no significant difference in tumor recurrence rate or tumor recurrence site between the two groups either ( χ2=0.22, 1.86, P>0.05). Conclusion:After the learning curve, robotic pancreato-duodenectomy has non-inferior prognosis compared with open pancreatoduodenectomy.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver diseases worldwide and covers a series of pathological manifestations from hepatic steatosis to inflammation, fibrosis, and even liver cirrhosis. NAFLD is associated with a wide range of extrahepatic diseases, including metabolic syndrome, cardiovascular disease, chronic kidney disease, endocrine diseases, obstructive sleep apnea-hypopnea syndrome, psoriasis, and skeleton-muscle diseases. The major causes of death in patients with NAFLD include cardiovascular disease, malignancies, and liver-related complications, suggesting that extrahepatic diseases associated with NAFLD should be taken seriously by clinicians. This article reviews the research advances in extrahepatic diseases associated with NAFLD, so as to provide ideas for clinical assessment and treatment.

Objective:To summarize the clinical characteristics of central nerve system (CNS) infection and grasp the necessity and possibility of early diagnosis and precise intervention of CNS infection after renal transplantation.Methods:This retrospective study enrolled consecutive recipients of renal transplantation with CNS infection after transplant between January 2000 and December 2020. Correlative factors for CNS infection after renal transplant were determined by comparing the clinical data between recipients with and without CNS infection. After screening 3, 199 consecutive renal transplant recipients, 12 patients with CNS infection post-transplant were identified and recruited. The median age-of-onset was 48.5 (23-65) years. And the median time to disease onset after transplant was 50.5(1-204) months. The most common symptoms of CNS infection after renal transplant included fever (75.00%), consciousness disorder (58.33%), headache (58.33%) and neck rigidity (41.67%).Results:Hepatitis B virus carrier and pulmonary infection were correlated with CNS infection after transplantation ( P<0.05). Nine patients failed to identify the pathogen and only received empirical anti-infective regimen. The outcomes were curing ( n=3) and death ( n=6). Metagenomic sequencing was performed for identifying the pathogen in three recipients and actively adjusting the anti-infective regimen. As a result, 2 were cured and 1 died. The overall mortality was 58.33%. The median time to death or curing from disease onset were 20(2-19) and 25(16-35) days respectively in surviving and non-surviving recipients. Conclusions:The progress of CNS infection after transplantation is rapid with a high mortality. HBV carrier and pulmonary infection are possible risk factors of CNS infection after renal transplantation. Early pathogenic identification and precise etiological intervention are vital for better clinical outcomes.