Objective: To investigate the regional differences in the incidence of urothelial carcinoma among kidney transplant recipients between northern and southern China，so as to provide reference for early diagnosis of this disease. Methods: A comprehensive search was conducted across multiple databases，including CNKI，Wanfang，CBM，and PubMed，using the keywords “kidney transplantation” and “tumor” to collect clinical data from qualified kidney transplant centers.The latest and most complete literature data published by 17 transplant centers in northern China and 14 in southern China were included.Statistical analyses were performed to compare the incidence of post-transplant urothelial carcinoma and non-urothelial malignancies. Results: A total of 37 475 kidney transplant recipients were included，among whom 837 (2.23%) developed post-transplant malignancies，including urothelial carcinoma (366/837，43.73%)，non-urothelial carcinoma (444/837，53.05%)，and malignancies with unspecified pathology (27/837，3.23%).The incidence of malignancies was significantly higher in northern China than in southern China [(2.82±1.39)% vs. (1.67±0.83)%，P=0.011]，with a particularly pronounced difference in the incidence of urothelial carcinoma [(1.68±1.12)% vs. (0.32±0.32)%，P<0.001].No significant difference was observed in the incidence of non-urothelial carcinoma between the two regions [(1.11±0.56)% vs. (1.35±0.65)%，P=0.279].Additionally，female transplant recipients exhibited a higher incidence of malignancies than males in both regions (southern China：2.38% vs. 1.80%; northern China：8.93% vs. 2.52%). Conclusion: The incidence of urothelial carcinoma following kidney transplantation is significantly higher in northern China than in southern China，underscoring the importance of implementing regular tumor screening for kidney transplant recipients，particularly for female patients in northern China，to facilitate early diagnosis and timely intervention.

Objective:To analyze the short-term efficacy and safety of tislelizumab combined with neoadjuvant chemotherapy in the treatment of resectable esophageal squamous cell carcinoma (ESCC) .Methods:The clinical data of 56 patients with ESCC who received neoadjuvant therapy combined with surgical resection in the Department of Thoracic Surgery, Affiliated Hospital of Guangdong Medical University from April 2021 to October 2023 were collected. According to the different preoperative neoadjuvant therapy methods, the patients were divided into neoadjuvant chemotherapy combined with immunotherapy group (chemoimmunization group, n=24) and neoadjuvant chemotherapy group (chemotherapy group, n=32). The postoperative tumor regression grade, objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR) rate, major pathological remssion (MPR) rate, R0 resection rate, perioperative indicators, and security were compared between the two groups. Results:In chemoimmunization group, the tumor regression grade was better than that in chemotherapy group, with a statistically significant difference ( Z=9.39, P=0.025). The ORR and the DCR were 75.00% (18/24) and 91.67% (22/24) in chemoimmunization group, and 46.88% (15/32) and 65.62% (21/32) in chemotherapy group, with statistically significant differences ( χ2=4.48, P=0.034; χ2=5.21, P=0.022). The R0 resection rate was 87.50% (21/24) in chemoimmunization group, which was higher than that of the chemotherapy group [59.38% (19/32) ], with a statistically significant difference ( χ2=5.31, P=0.021). The pCR rate and MPR rate were 29.17% (7/24) and 54.17% (13/24) in chemoimmunization group, and 6.25% (2/32) and 28.12% (9/32) in chemotherapy group, there was no statistically significant difference in pCR rate ( χ2=3.78, P=0.052), but there was a statistically significant difference in MPR rate ( χ2=3.89, P=0.048). The interval between the end of neoadjuvant treatment and the start of surgery was (42.71±8.29) days in chemoimmunization group, and (42.25±8.03) days in chemotherapy group. The intraoperative blood loss of patients was (215.54±57.85) ml in chemoimmunization group, and (229.65±57.74) ml in chemotherapy group. The operation time of patients was (293.52±37.50) minutes in chemoimmunization group, and (295.31±37.66) minutes in chemotherapy group. The postoperative hospitalization time of patients was (17.90±3.49) days in chemoimmunization group, and (18.42±3.82) days in chemotherapy group, all with no statistically significant differences ( t=0.21, P=0.835; t=0.90, P=0.370; t=0.18, P=0.861; t=0.52, P=0.603). In terms of postoperative complications, there was no statistically significant difference in the total incidence of postoperative complications between the two groups [62.50% (15/24) vs. 84.38% (27/32), χ2=0.59, P=0.440]. The main adverse drug reactions in the two groups included decreased white blood cell count, nausea and vomiting, liver dysfunction, pruritus, hypothyroidism, etc. Most of them were grade 1-2, 3 cases were grade 3, and no grade 4 adverse reactions occurred. The total incidence of adverse reactions was 62.50% (15/24) in chemoimmunization group, and 65.62% (21/32) in chemotherapy group, with no statistically significant difference ( χ2=0.06, P=0.809) . Conclusion:For the preoperative neoadjuvant therapy of resectable ESCC, the combination of tislelizumab and chemotherapy has better short-term efficacy and better safety than the single chemotherapy scheme, which can improve the surgical efficacy.

Objective To investigate the expression of 8-hydroxy deoxy guanosine(8-OHdG)and nectin-4 in the serum of primary liver cancer(PLC),and to evaluate the efficacy of transcatheter chemoembolization(TACE)for PLC.Methods From January 2021 to June 2022,180 patients with primary liver cancer with TACE were studied.According to the efficacy of TACE patients,they were separated into a good group(n=137)and an adverse group(n=43).The general clinical data and the serum expression levels of 8-OHdG and nectin-4 were compared between the two groups;multivariate Logistic regression was applied to analyze the influencing factors of postoperative efficacy in TACE for primary liver cancer;receiver operating characteristic was applied to analyze the value of serum 8-OHdG and nectin-4 levels in evaluating the efficacy of TACE for primary liver cancer.Results There were no significant differences in age,sex,BMI,Child-Pugh grade,tumor location,tumor number,tumor diameter,tumor contour,degree of differentiation,tumor envelope,vascular cancer thrombus,bile duct cancer thrombus and lymph node metastasis between the poor postoperative efficacy group and the good efficacy group after TACE for primary liver cancer(P＞0.05).The expression levels of serum 8-OHdG and nectin-4 in the poor postoperative efficacy group after TACE for primary liver cancer were obviously higher than those in the good efficacy group(P＜0.05).Multivariate Logistic regression analysis showed that serum 8-OHdG,nectin-4,tumor diameter,TNM staging and Lymph node metastasis were all independent influencing factors for the postoperative efficacy of TACE in primary liver cancer(P＜0.05).The AUC of the combined evaluation of serum 8-OHdG and nectin-4 for the postoperative efficacy of TACE in primary liver cancer was 0.930,with a sensitivity of 86.05％and a specificity of 94.16％,which was superior to their respective individual evaluations(Zcombination-8-OHdG=2.033,Zcombination-nectin-4=3.221,P=0.042,0.001).Conclusion The serum levels of 8-OHdG and nectin-4 are obviously increased in the poor postoperative efficacy group after TACE for primary liver cancer.The combination of the two has a good evaluation effect on the postoperative efficacy of TACE for primary liver cancer.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Humans ; Carcinogenesis/genetics* ; Gene Expression Regulation, Neoplastic ; Genes, cdc ; Nasopharyngeal Carcinoma/genetics* ; Nasopharyngeal Neoplasms/genetics* ; RNA Helicases/metabolism*

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

Objective To investigate the clinical effect of percutaneous transhepatic drainage combined with sequential percutaneous nephroscopy for necrosectomy and drainage in the treatment of refractory liver abscess after transcatheter arterial embolization (TACE). Methods A retrospective analysis was performed for three patients with refractory liver abscess after TACE in The Affiliated 3201 Hospital of Xi'an Jiaotong University School of Medicine from January 2018 to December 2020, and among the three patients, one had the formation of liver abscess after TACE for hepatic metastases after pancreaticoduodenectomy, one had liver abscess after repeated TACE for massive hepatocellular carcinoma, and one had secondary liver abscess after TACE for traumatic hepatic rupture. All three patients received percutaneous transhepatic drainage and sequential percutaneous nephroscopy for the treatment of refractory liver abscess, and their specific treatment process was summarized. Results All three patients were diagnosed with refractory liver abscess based on CT, routine blood test, procalcitonin, blood culture, and clinical manifestation. Percutaneous transhepatic catheterization under the guidance of conventional ultrasonography or CT and effective antibiotics had an unsatisfactory therapeutic effect, and after sequential percutaneous nephroscopy was performed for necrosectomy and drainage, liver abscess was cured and the patients had good prognosis. Conclusion For refractory liver abscess after TACE, when routine puncture treatment has an unsatisfactory therapeutic effect or a patient cannot tolerate surgical operation, percutaneous transhepatic drainage combined with sequential percutaneous nephroscopy is safe and effective in the treatment of refractory liver abscess.

Objective To investigate the clinical effect of two-step percutaneous transhepatic choledochoscopic lithotomy (PTCSL) in the treatment of complex hepatolithiasis. Methods A retrospective analysis was performed for the clinical data of 118 patients with complex hepatolithiasis who were admitted to 3201 Hospital of Xi'an Jiaotong University Health Science Center from January 2018 to June 2020, and according to the surgical procedure, they were divided into PTCSL group with 60 patients and surgery group with 58 patients. All patients were followed up for half a year to 3 years via telephone and outpatient service. The two groups were compared in terms of general information, perioperative indicators (including time of operation, intraoperative blood loss, incision length, time to first flatus and time to first defecation after surgery, time to extraction of abdominal drainage tube, and length of hospital stay), changes in liver function and inflammatory indicators, postoperative complications (bile leakage, acute cholangitis, wound infection, and venous thrombosis of lower extremities), stone clearance rate and recurrence rate, and quality of life. The two-independent-samples t -test was used for comparison of continuous data between two groups; the paired t -test was used for comparison between different periods of time within group; the chi-square test was used for comparison of categorical data between two groups. Results Compared with the surgery group, the PTCSL group had significantly shorter time of operation, time to first flatus and time to first defecation after surgery, and time to extraction of abdominal drainage tube, a significantly lower intraoperative blood loss, and a significantly shorter incision length (all P < 0.05). On day 1 after surgery, both groups had significant reductions in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ( P < 0.05) and a significant increase in white blood cell count (WBC) ( P < 0.05), and the PTCSL group had significantly lower levels of ALT, AST, and WBC than the surgery group (all P < 0.05). Compared with the surgery group, the PTCSL group had significantly lower incidence rates of postoperative bile leakage (5.0% vs 17.2%, P < 0.05), acute cholangitis (3.3% vs 13.8%, P < 0.05), wound infection (1.7% vs 10.3%, P < 0.05), and venous thrombosis of lower extremities (1.7% vs 12.1%, P < 0.05). Compared with the surgery group, the PTCSL group had a significantly higher stone clearance rate (58.3% vs 37.9%, P < 0.05) and a significantly lower long-term stone recurrence rate (10.0% vs 20.7%, P < 0.05). The PTCSL group had significantly higher quality of life scores than the surgery group (all P < 0.05). Conclusion For the treatment of complex hepatolithiasis, two-step PTCSL can effectively remove stones, with the advantages of fast postoperative recovery, low recurrence rate and incidence rate of complications, and high quality of life, and therefore, it is an effective alternative surgical procedure.

Objective To investigate the relationship between preoperative urodynamic parameters and the improvement of overactive bladder (OAB)symptoms after GreenLight laser vaporization,and to explore prognostic factors for improvement of OAB symptoms in the elderly.Methods A retrospective study was conducted in 100 benign prostatic hyperplasia (BPH)patients undergoing GreenLight laser vaporization at the Department of Urology of Beijing Hospital from July 2015 to March 2017.All patients completed a preoperative urodynamic examination and received GreenLight laser vaporization.Clinical data including age,prostate-specific antigen (PSA),prostate volume,international prognostic scoring system(IPSS),overactive bladder symptom score (OABSS),quality of life(QOL)and urodynamic parameters were collected.The related factors for improvement of OAB symptoms after GreenLight laser vaporization were analyzed by a binary Logistic regression analysis.Results All patients underwent surgery successfully and completed a 12-month follow-up.Both urinary storage and voiding symptoms improved at 3 and 12 months after GreenLight laser vaporization(P＜0.05).The scores of IPSS,IPSS storage (IPSS-S),IPSS voiding (IPSS-V),OABSS and QOL and nighttime voiding frequency decreased and urinary storage and voiding symptoms improved at 3 and 12 months after GreenLight laser vaporization,compared with pre-surgery data(P＜0.05).The success rates of storage symptom improvement at 3 and 12 months after GreenLight laser vaporization were 62.0 ％ (62/100) and 68.0 ％ (68/100) evaluated by IPSS-S and 68.0 ％ (68/100) and 75.0％ (75/100)by OABSS,respectively.Multiple Logistic regression analysis showed that age,detrusor contractility,residual urine volume and nighttime voiding frequency were independent influencing factors for prognosis(OR =35.714,0.352,0.110 and 0.040,P =0.000,0.027,0.018 and 0.002).Conclusions GreenLight laser vaporization is an effective method in treating BPH with OAB.Age is an independent unfavorable factor and the residual urine volume,nighttime voiding frequency and detrusor contraction are independent influencing factors for prognosis.Enough attention should be paid to these related parameters before surgery.