Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Objective To develop a deep learning model for automated age estimation based on 3D CT reconstructed images of Han population in western China,and evaluate its feasibility and reliability.Methods The retrospective pelvic CT imaging data of 1 200 samples(600 males and 600 females)aged 20.0 to 80.0 years in western China were collected and reconstructed into 3D virtual bone models.The images of the ischial tuberosity feature region were extracted to create sex-specific and left/right site-specific sample libraries.Using the ResNet34 model,500 samples of different sexes were randomly selected as training and verification set,the remaining samples were used as testing set.Initialization and transfer learning were used to train images that distinguish sex and left/right site.Mean absolute error(MAE)and root mean square error(RMSE)were used as primary indicators to evaluate the model.Results Prediction results varied between sexes,with bilateral models outperformed left/right unilateral ones,and transfer learning models showed superior performance over initial models.In the prediction results of bilateral transfer learning models,the male MAE was 7.74 years and RMSE was 9.73 years,the female MAE was 6.27 years and RMSE was 7.82 years,and the mixed sexes MAE was 6.64 years and RMSE was 8.43 years.Conclusion The skeletal age estimation model,utilizing is-chial tuberosity images of Han population in western China and employing the ResNet34 combined with transfer learning,can effectively estimate adult ischium age.

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.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective:To retrospectively summarize disease characteristics and the clinical experience of minimally invasive endoscopy in the treatment of upper urinary tract obstruction caused by ureteropelvic encrusted inflammatory disease.Methods:Three patients with bilateral ureteropelvic encrusted inflammatory disease admitted to our hospital from March 2018 to July 2021 were involved. Case 1, male, 45 years old, admitted due to bilateral hydronephrosis for 5 months. The preoperative diagnosis were bilateral ureteropelvic stones (encrustation), right ureteral atresia, left ureteral stenosis, and systemic vasculitis. Left double J tube insertion and right nephrostomy were performed in another hospital. We conducted antegrade percutaneous nephroscopy combined with retrograde ureteroscopy surgery and assisted balloon dilation to treat bilateral lesions stage by stage. Case 2, Male, 12 years old, admitted due to bilateral abdominal pain for 6 weeks. The preoperative diagnosis were bilateral ureteral stones, bilateral hydronephrosis, and dermatomyositis. After the failure of double J tube insertion in another hospital, double nephrostomy was performed instead. We performed left percutaneous nephroscopy and right percutaneous nephroscopy combined with ureteroscopy for the treatment of bilateral lesions. Case 3, female, 32 years old, was admitted because of pain in the left lower back and abdomen for over 6 months. The preoperative diagnosis were bilateral ureteral stones, bilateral ureteral stenosis, and dermatomyositis. She underwent three times of ESWL and once URS before. We performed ureteroscopic surgery for bilateral lesions. During the surgery, various degrees of crusting in the renal pelvis or ureter were observed in all 3 cases, and the lesions were removed using pneumatic lithotripsy combined with forceps or baskets. After surgery, oral antibiotics were continuously used for 1-3 months. The efficacy and prognosis were evaluated based on the follow-up of urine, imaging, and endoscopic examinations at 3, 6, and 12 months after surgery.Results:All 3 surgeries were successfully completed. At 3, 6, and 12 months after surgery, follow-up CT showed no crusting in the left ureter, and endoscopy showed good mucosal wound healing and unobstructed lumen in case 1. There were still some crusting lesions and lumen stenosis in the right renal pelvis, and the right ureter reconstruction surgery was ultimately performed. There were no crusting on both sides and the urinary tract was unobstructed after 3, 6, and 12 months of follow-up in case 2 and case 3. Postoperative pathological examination showed chronic inflammation of urothelial mucosal tissue, small pieces of proliferative fibrous tissue with peripheral calcification. Calcification layer composition analysis showed magnesium ammonium phosphate and carbonate apatite. No related complications occurred in case 2 and case 3.Conclusions:Urothelial crusted inflammatory disease is rare clinically, and the diagnosis and treatment strategies are rarely reported domestically and internationally. Preoperative imaging examination, intraoperative findings and postoperative pathology or calcification composition analysis are of instruction for the diagnosis and treatment of this disease. Minimally invasive endoscopy treatment for upper urinary tract obstruction caused by ureteropelvic encrusted inflammatory disease has a good effect. Long-term efficacy and other adjuvant treatment need long-term follow-up and clinical practice.

ObjectiveThe purpose of this study was to evaluate the functional outcomes and satisfaction in periprosthetic knee infection patients after above-the-knee amputation （AKA）. MethodsA review was performed in 13 patients who underwent AKA due to periprosthetic knee infection from October 2010 to August 2022， there were 7 females and 6 males with the median age of 69 （45~ 73） years. The mean number of surgical procedures between primary total knee arthroplasty and AKA was 2.9 times （range： 1 ~ 6）. Patients were segregated into non-elderly group （including patients <65 years old） and elderly group （involving patients ≥65 years old）. Functional outcomes were evaluated by SF-12 and Barthel activities daily living index （Barthel ADL index）. Patient satisfaction was accomplished through a questionnaire. ResultsFour patients died within 6 months after the amputation. Three patients received surgical procedures for recurrent infections after AKA. In the remaining 9 patients，the median time from AKA to the final follow-up was 4.2 （1.9~8.2） years， three patients received surgical procedures for recurrent infections after AKA. Patients in non-elderly group showed better functional outcomes than elderly patients after AKA （both P<0.05）. All patients in non-elderly group were fitted with a prosthesis. Whereas， elderly patients reported a better satisfaction after AKA than young patients. ConclusionYoung PJI patients seemed to have better function and ambulatory ability with high expectation and demand， which made them feel less satisfied about AKA. Meanwhile，despite poor function outcomes due to the less healthy physical condition， the alleviation of financial and psychological burdens resulting from reinfections and multiple surgeries and the less demand in function and daily activities made elderly patients have a good satisfaction after AKA.

italic>Tussilago farfara L. is a perennial herb of Tussilago genus in the Compositae family. Its dried buds and leaves have good biological activities and have a long history of medicinal use in China and Europe. In this paper, we investigated the whole chloroplast genome characteristics, sequence duplication, structural variation and phylogeny of the Tussilago farfara L. After sequencing the Tussilago farfara L. chloroplast genome using Illumination technology, the complete Tussilago farfara L. chloroplast genome was further obtained by assembly and annotation, followed by a series of inverted repeat-large single copy/small single copy region contraction and expansion analysis, genome sequence variation, etc. The sequences of 13 homologous plants downloaded from NCBI were used to construct a neighbor-joining phylogenetic tree. The results showed that the total GC content of the chloroplast genome was 37.4% and the length was 150 300 bp; 125 genes were annotated, including 82 protein-coding genes, 35 tRNAs and 8 rRNAs; 148 (simple sequence repeats, SSR) loci were detected, and the relative synonymous codon usage showed that 31 codons out of 64 codons had a usage of >1. In the phylogenetic analysis, the chloroplast genomes of the seven species of Asteraceae, including the Yulin Tussilago farfara L., were highly conserved, and the sequence variation of the (large single-copy, LSC) and (small single-copy, SSC) regions was higher than that of the (inverted repeat, IR) region. This is in general agreement with the reported phylogeny of Yulin Tussilago farfara L. In this study, we obtained a high quality chloroplast genome and analyzed its genome characteristics, codon preference, SSR characteristics, SC/IR boundary, sequence variation and phylogeny, which can provide a basis for species identification, genetic diversity analysis and resource development of this medicinal plant.

To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.

Objective:To summarize the preliminary clinical experience of utilizing ureteral balloon dilation catheter in the treatment of "difficult ureter" during ureteroscopic lithotripsy, and to discuss the efficacy and safety of the technique.Methods:Clinical data of 28 patients (30 sides) with upper urinary tract calculi admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from April 2021 to July 2022 were retrospectively analyzed. There were 23 males (82.1%) and 5 females (17.9%), with age of (51.5±13.6) years. Among the 30 sides, 20 (66.7%) on the left and 10(33.3%) were on the right. Calculi were either located in the renal pelvis or calyxes in 7 sides (23.3%), upper ureter in 17 sides (56.7%), and lower ureter in 6 sides (20.0%). The maximum diameter of the stones was (9.4±4.2)mm, and 23 sides (76.7%) were combined with hydronephrosis before surgery. When "difficult ureter" was encountered during the procedure, that is, it was difficult to insert ureteroscope or ureteral access sheath (UAS) due to small ureteral lumen, balloon catheter was used for dilation in the first stage, in which the balloon diameter was 4 mm on 22 sides and 5mm on 8 sides. The instrument was retrogradely inserted through the working channel of F8 semi-rigid ureteroscope, and the small site of the ureteral lumen was dilated under direct endoscopic view. After a single dilation, the balloon catheter was withdrawn, and the effect of dilation was evaluated by semi-rigid ureteroscopy to determine whether to proceed with the following procedures. The intraoperative data were recorded, including surgical method, stage of "difficult ureter" occurred, site of the small part of the ureter, related data of utilizing ureteral dilatation balloon catheter, grade of ureteral injury after dilatation (according to the 0-4 grading classification of endoscopic ureteral injuries), total operation time, balloon catheter-related adverse events, stone-free rate, and time of removing ureteral stents.Results:Among the 30 sides, 29 (96.7%) had difficulty in the stage of ureteroscope insertion, and 1(3.3%) had difficulty in the stage of UAS insertion. A total of 37 small sites of ureter were involved, including 18 in the intramural segment, 10 in the lower part, 2 in the middle part, and 7 in the upper part. Each site was dilated once with a median time of 3 (0.5, 5.0) minutes and a median maximum balloon pressure of 1 215.9(1 215.9, 1 443.9)kPa[12.0(12.0, 14.3)atm]. There were 28 sites of grade Ⅰ injury, 8 sites of grade Ⅱinjury, and 1 site of grade Ⅲinjury. The total duration of unilateral procedure was (73.4±30.3) min. Ureteroscope or UAS insertion was successful in 28 sides(93.3%) after balloon dilation, and failed in 2 sides(6.7%), both of which were in the stage of inserting ureteroscope and ureteral stent was indwelled for the second-stage procedures. On the first day after surgery, the hemoglobin level was (134.1±12.9)g/L, which was significantly different from the preoperative parameters ( P<0.01), and serum creatinine level was (86.7±23.2)μmol/L, which showed no significant difference from the preoperative one ( P=0.263). The primary stone-free rate was 92.9% (26/28), and the total postoperative complication rate was 13.3% (4/30), including 3 of grade Ⅰ (lateral lower abdominal pain requiring additional analgesic drugs) and 1 of grade Ⅱ (postoperative hematuria requiring intravenous hemostatic drugs). Follow-up was conducted for 3 months. All of the 28 successful sides had their ureteral stents removed before the last follow-up, and the time of removal was (36.9±11.5) days. No hydronephrosis was found in the ipsilateral kidney by ultrasound 3 months after operation. Conclusions:Balloon dilation technique showed good efficacy and safety in the treatment of "difficult ureter" during ureteroscopic lithotripsy.