Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome, with implications for microbial pathogenesis and host defense. Among these, transfer RNA-derived small RNAs (tsRNAs) have garnered attention for their roles in modulating microbial behavior. However, the bacterial factors mediating tsRNA interaction and functionality remain poorly understood. In this study, using RNA affinity pull-down assay in combination with mass spectrometry, we identified a putative membrane-bound protein, annotated as P-type ATPase transporter (PtaT) in Fusobacterium nucleatum (Fn), which binds Fn-targeting tsRNAs in a sequence-specific manner. Through targeted mutagenesis and phenotypic characterization, we showed that in both the Fn type strain and a clinical tumor isolate, deletion of ptaT led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition. Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between Fn wild type and PtaT-deficient mutant, highlighting the functional significance of PtaT in purine and pyrimidine metabolism. Furthermore, AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and Fn-targeting tsRNA. By uncovering the first RNA-binding protein in Fn implicated in growth modulation through interactions with host-derived small RNAs (sRNAs), our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.
Fusobacterium nucleatum/growth & development* ; RNA-Binding Proteins/genetics* ; Bacterial Proteins/genetics* ; RNA, Bacterial/metabolism* ; Humans ; RNA, Transfer/metabolism*

Objective To investigate the changes in the tumor microenvironment of pancreatic cancer(PDAC)complicated with diabetes mellitus(DM)in a mouse model of hyperglycemia and orthotopic pancreatic cancer by analyzing transcriptome and single-cell transcriptome data in order to identify potential therapeutic targets.Method By integrating single-cell transcriptome and bulk transcriptome data,bioinformatics analysis was conducted to compare the characteristics of tumor cells and tumor immune microenvironment between PDAC patients with DM(DM group)and those without DM(non-DM group).Twenty male C57BL/6 mice(6 weeks old,weighing 18～20 g)were randomly divided into a hyperglycemic group[STZ group,continuous intraperitoneal injection of 50 mg/kg streptozocin(STZ)(final concentration of 1％)dissolved in citrate buffer],and a control group(Control group,an equivalent volume of citrate buffer without STZ at the same time points),with 10 mice in each group.Tail-tip blood glucose level was measured to monitor glycemic status.After orthotopic inoculation of pancreatic cancer cells in both Control and STZ groups,tumor-infiltrating immune cells were harvested.Flow cytometry was employed to determine the effects of hyperglycemia on:total CD8+T cell and Treg cell populations;CD8+T cell subsets expressing Ki67,TNF-α,granzyme B(GZMB)and IFN-γ;surface expression of PD-1,lymphocyte activation gene-3(LAG-3)and T cell immunoglobulin and mucin domain-3(Tim-3)on CD8+T cells;programmed death-ligand 1(PD-L1)expression on tumor cells;and tumor-associated macrophage surface expression of major histocompatibility complex classⅠ(MHC-Ⅰ)and cluster of differentiation 206(CD206).Results Bioinformatics analysis revealed that,compared to the non-DM group,the genes significantly up-regulated in the DM group were associated with poor prognosis(P＜0.001).The proportion of type 2 ductal cells was increased in the DM group,exhibiting higher levels of copy number variation(P＜0.001).In the tumor immune microenvironment of the DM group,there was an increase in the proportion of Treg cells(P＜0.05)and an elevated exhaustion score for CD8+T cells(P＜0.001),accompanied by down-regulated expression of effector molecules,up-regulated expression of inhibitory checkpoints,and a significant increase in the M2 score of M2-like macrophages(P＜0.001).Animal experiments and flow cytometry found that,compared to the Control group,the STZ group had a shorter survival time(P＜0.001),with decreased proportions of total CD8+T cells(P＜0.01)and CD8+T cells expressing Ki67,TNF-α,GZMB and IFN-γ(P＜0.01),increased proportion of Treg cells(P＜0.001),up-regulated expression of PD-1,LAG-3 and Tim-3 on the surface of CD8+T cells(P＜0.001),and up-regulation of PD-L1 on tumor cell surface(P＜0.001)and enhanced expression of CD206 on the surface of tumor-associated macrophages,while down-regulated expression of MHC-Ⅰ(P＜0.001).Conclusion High glucose promotes the formation of an immunosuppressive microenvironment in PDAC,and targeting type 2 ductal cells and immunosuppressive cells in the tumor microenvironment,combined with dual immune checkpoint antibody therapy,may improve patient prognosis.

Objective:To investigate the feasibility,safety and effectiveness of robot-assisted laparo-scopic buccal mucosa graft ureteroplasty in the treatment of complex long proximal ureteral stricture.Methods:The clinical data of 20 patients with proximal ureteral stricture undergoing robot-assisted lapa-roscopic buccal mucosa graft ureteroplasty admitted to the Department of Urology,Peking University First Hospital and Beijing Jiangong Hospital from July 2022 to January 2023 were prospectively collected and analyzed.Intraoperative conditions,postoperative complications and follow-up data were also recorded and analyzed.Results:The operations under robot-assisted laparoscopy were performed successfully in all the 20 patients without conversion to traditional laparoscopic surgery or open surgery.The study in-cluded 14 males and 6 females with a mean age of(41±11)years(range:19 to 60 years)and a mean body mass index of(24.3±3.6)kg/m2(range:18.2 to 31.8 kg/m2).There were 9 cases on the left side and 11 cases on the right side.The strictures of all the patients were located in the proximal segment of the ureter(including the ureteropelvic junction).The mean preoperative serum creatinine was(92.2±23.3)μmol/L(range:49.2 to 138.9 μmol/L),and the mean length of ureteral stricture was(2.8±0.9)cm(range:1.0 to 4.0 cm).Ten patients had previously undergone unsuccessful reconstructive surgery.During the operation,12 patients received posteriorly augmented anastomosis with ventral onlay.The mean length of the buccal mucosa graft harvested during the operation was(3.1±0.6)cm(range:2.0 to 4.3 cm),and the median width was 1.5 cm(range:1.0 to 2.0 cm).The omentum flap was used to wrap the reconstructed ureteral segment in all the 20 cases.The median operative time was 154 min(range:113 to 300 min),and the median estimated blood loss was 45 mL(range:0 to 100 mL).The median postoperative hospital stay was 4 d(range:4 to 14 d).The mean postoperative follow-up time was(15.0±1.7)months(range:12.5 to 17.9 months),and the surgical success rate was 100.0％in this study.After surgery,11 patients reported mild discomfort at the oral donor site,2 patients deve-loped urinary tract infection,and no postoperative complications were reported in the other 7 patients.The mean serum creatinine was(90.9±23.9)μmol/L(range:60.0 to 153.0 μmol/L)six months after surgery.Conclusion:Robot-assisted laparoscopic buccal mucosa graft ureteroplasty for the treatment of complex long proximal ureteral stricture has satisfactory efficacy without severe complications,which has shown good feasibility,safety and effectiveness.However,large sample studies and long-term follow-up are still needed to evaluate its long-term efficacy.

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.

The basic concept and related background of multivariate statistical process control(MSPC)were intro-duced.The basic process of MSPC implementation and the common statistics and control charts were described.The important role of MSPC in the pharmaceutical production process was emphasized,especially in the field of tra-ditional Chinese medicine,providing reference for the selection of quality control methods in drug production process.The advantages and disadvantages of MSPC were summarized,and the development trend of MSPC in drug production and quality control was prospected.

【Objective】 To investigate the common etiology, characteristics and treatment of iatrogenic ureteral stricture. 【Methods】 The clinical data of 226 patients with ureteral stricture repaired during May 2019 and Mar. 2022 were retrospectively analyzed, including 68 cases of iatrogenic ureteral stricture. According to the etiology, the patients were divided into urinary group and non-urinary group. 【Results】 There were 42 females and 26 males, aged 25 to 67 (average 49.0±10.4) years. Upper ureteral stricture was detected in 24 (35.3%) cases, who received oral mucosal repair of the ureter. Middle ureteral stricture was detected in 12 (17.6%) cases, who underwent ileal ureterography. Lower ureteral stricture was observed in 24 (35.3%) cases, who were treated with vesical wall flap ureteroplasty. Full-length stricture was observed in 8 (11.8%) cases,who were treated with ileal ureterography. There were significant differences in age, gender, stenosis side, stenosis location and length, surgical methods and types between patients in the urinary group and non-urinary group (P<0.05). During the follow-up of 8 to 20 (average 12.3±5.6) months, the symptoms and renal function of all patients improved, and no recurrence occurred. 【Conclusion】 Invasive endourological surgery is the most common cause of iatrogenic ureteral stenosis. Different treatment strategies should be adopted according to patients’ condition, time of diagnosis and location and length of ureteral injury.

【Objective】 To explore the feasibility of using autoregressive moving average model (ARIMA) to predict the dosage of suspended red blood cells in children, and to provide a basis for the development of clinical blood reserve plans in children's hospitals. 【Methods】 ARIMA model was constructed using the total blood consumption of clinical suspended red blood cells from March 2016 to May 2022 at the Children's Hospital of Chongqing Medical University as the data source by SPSS26.0 software. The optimal model was used to predict the clinical suspended red blood cell consumption from June to October 2022, and the predictive effect of the model was tested. 【Results】 ARIMA(0, 1, 1) (0, 1, 1)12 was the optimal model for predicting the consumption of suspended red blood cells in pediatrics. The autocorrelation function and partial autocorrelation function of the residual sequence basically fell within the 95% confidence interval. At the same time, Ljung-Box Q statistical results showed that there was no correlation between the residual (P>0.05), indicating that the residual was white noise, which met the randomicity hypothesis. The average relative error between the predicted values of the model and the actual clinical red blood cell usage from June to October 2022 was 5%, indicating high prediction accuracy. 【Conclusion】 The blood usage of children has obvious seasonal and periodic patterns, and the optimal model ARIMA (0, 1, 1) (0, 1, 1)12 can better fit the trend of changes in pediatric suspended red blood cell usage, thus providing a basis for the development of clinical blood reserve plans in children's hospitals.

Objective:To investigate the clinicopathologic features and differential diagnosis of ureteral fibroepithelial polyps.Methods:The clinicopathologic features and prognosis of ureteral fibroepithelial polyps with complete data retrieved from the pathology database of the Institute of Urology, Peking University from January 2013 to December 2021 were collected and analyzed. All HE staining sections were reviewed by a senior urologic pathologist. Immunohistochemical analysis was done in some cases for differential diagnosis. The clinical, imaging and outcome data were collected, and discussed together with relevant literature.Results:There were 45 patients with complete clinicopathologic data, including 34 males and 11 females (male: female=3.1∶1.0), with a median age of 36 (range 13-80) years. Preoperative diagnosis included polyp in 23 cases, tumor in 19 cases and calculi in 3 cases. The main clinical symptoms were hematuria (13 cases), low back and abdominal pain (9 cases) and no symptoms (9 cases). There were 29 cases of multiple polyps, 16 cases of single polyp; 32 cases were on the left side, 13 cases were on the right side; 29 cases of upper polyps, 9 cases of middle polyps, and 6 cases of lower polyps. Twenty-seven patients had no related urologic history, 10 patients had history of urolithiasis, and the rest had history of stents, strictures or tumors. Local ureteral resection and anastomosis were the most common treatment (20 cases), followed by ureteroscopic polypectomy (12 cases). The patients were followed up from the pathological diagnosis to the cut-off time: 4 cases were lost to follow-up, and the remaining 34 cases were followed up for 3 to 85 (mean 60 months). One case had polyp recurrence after 3 months, and the other case had polyp recurrence after 2 years. Fibroepithelial polyps had a variety of gross manifestations, ranging from elongated polyps or small papillary and polypoid to large papillary masses. Microscopically, they were divided into type 1, type 2 and type 3, and the type 3 was the most common type (28 cases). In this study, there were 41 cases of simple fibroepithelial polyp, 2 cases of malignant transformation of polyps into urothelial carcinoma, one case of polyps with urothelial carcinoma, and one case of polyp with surface urothelial carcinoma in situ; the stroma showed myofibroblastic proliferation.Conclusions:The clinical manifestations and morphologic characteristics of ureteral fibroepithelial polyps are diverse. The three microscopic types are easily confused with many benign and malignant ureteral diseases, such as inflammatory polyps, adenocystitis, papilloma, etc. Awareness of the key differentiation points and judicious use of immunohistochemistry will be helpful for the diagnosis and differential diagnosis.