BACKGROUND:Traditional methods of urinary tract reconstruction are limited by donor scarcity,high complication rates,and suboptimal functional recovery.Tissue engineering strategies offer new directions in this field.Since the urinary tract is mainly composed of muscle tissue,the key is to find suitable seed cells and efficiently induce them to differentiate into smooth muscle cells.Comparative studies on the efficacy of different smooth muscle cell induction regimens are still lacking. OBJECTIVE:To isolate,culture,and identify human urine-derived stem cells,and to compare the effects of two different induction protocols. METHODS:Human urine-derived stem cells were isolated from urine samples of 11 healthy adult volunteers by multiple centrifugations.Surface markers were identified by flow cytometry.The multi-directional differentiation potential of human urine-derived stem cells was verified through osteogenic and adipogenic differentiation.Differentiation was induced by transforming growth factor-β1 or transforming growth factor-β1 combined with platelet derived growth factor for 14 days.Immunofluorescence staining and western blot assay were employed to compare the expression differences of smooth muscle-specific proteins(α-SMA and SM22). RESULTS AND CONCLUSION:(1)Urine-derived stem cells were successfully isolated from the eight urine samples of healthy people.These cells exhibit a"rice grain"-like morphology and possess a robust proliferative capacity.(2)Urine-derived stem cells exhibited high expression of mesenchymal stem cell surface markers(CD73,CD90,and CD44)and extremely low expression of hematopoietic stem cell surface markers(CD34 and CD45).These cells did not express CD19,CD105,and HLA-DR.(3)After osteogenic and adipogenic differentiation,the formation of calcium nodules and lipid droplets was observed,with positive staining results from Alizarin Red S and Oil Red O staining.(4)After 14 days of smooth muscle induction culture,immunofluorescence staining revealed that the smooth muscle differentiation rate of urine-derived stem cells treated with a combination of transforming growth factor-β1 and platelet derived growth factor was significantly higher compared to those treated with transforming growth factor-β1 alone(P<0.005).(5)After 14 days of smooth muscle induction culture,western blot assay further demonstrated that the expression levels of α-SMA and SM22 in the transforming growth factor-β1/platelet derived growth factor group were significantly elevated compared to those in the transforming growth factor-β1 only group(P<0.005).These findings confirm that urine-derived stem cells can be non-invasively isolated using multiple rounds of centrifugation.Compared with transforming growth factor-β1 alone,the combination of transforming growth factor-β1 and platelet derived growth factor can improve the efficiency of inducing urine-derived stem cells to differentiate into smooth muscle cells.

Objective To evaluate the bioequivalence of test product and reference product in a single dose of amoxicillin clavulanate potassium tablet under fasting and fed conditions in healthy volunteers.Methods An open label,randomized,single dose,four-period,crossover bioequivalence study was designed.Fasting and postprandial tests were randomly divided into 2 administration sequence groups according to 1:1 ratio,amoxicillin clavulanate potassium tablet test product or reference product 375 mg,oral administration separately,liquid chromatography tanden mass spectrometry was applied to determine the concentration of amoxicillin and clavulanate potassium in plasma of healthy subjects after fasting or fed administration,while Phoenix WinNonlin 8.2 software were used for pharmacokinetics(PK)parameters calculation and bioequivalence analysis.Results Healthy subjects took the test product and the reference product under fasting condition,the main PK parameters of amoxicillin are as follows:Cmax were(5 075.57±1 483.37)and(5 119.86±1 466.73)ng·mL-1,AUC0_twere(1.32 × 104±2 163.76)and(1.30 × 104±1 925.11)ng·mL-1,AUC0-∞were(1.32 × 104±2 175.40)and(1.31 ×104±1 935.86)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(3 298.27±1 315.23)and(3 264.06±1 492.82)ng·mL-1,AUC0-twere(7 690.06±3 053.40)and(7 538.39±3 155.89)ng·mL-1,AUC0-∞were(7 834.81±3 082.61)and(7 671.67±3 189.31)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-tand AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Healthy subjects took the test and reference product under fed condition,the main PK parameters of amoxicillin are as follows:Cmax were(4 514.08±1 324.18)and(4 602.82±1 366.48)ng·mL-1,AUC0-twere(1.15 × 104±1 637.95)and(1.15 × 104±1 665.69)ng·mL-1,AUC0-∞ were(1.16 × 104±1 646.26)and(1.15 × 104±1 607.20)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(2 654.75±1 358.29)and(2 850.51±1 526.31)ng·mL-1,AUC0-twere(5 882.82±2 930.06)and(6 161.28±3 263.20)ng·mL-1,AUC0-∞ were(6 022.70±2 965.05)and(6 298.31±3 287.63)ng·mL-1;the 90％confidence intervals of Cmax,AUC0-t and AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00％-125.00％.Conclusion The two formulations were bioequivalent to healthy adult volunteers under fasting and fed conditions.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To compare the application value of three image post-processing techniques volume rendering(VR),multiplanar reformation(MPR)and curved planar reformation(CPR)in the identifi-cation of rib fracture malunion.Methods The types and numbers of rib fracture malunion in 75 pa-tients were recorded,and the sensitivity,specificity,accuracy and Youden index of VR,MPR and CPR in the diagnosis of rib fracture malunion were compared.Receiver operator characteristic(ROC)curve was drawn and area under the curve(AUC)was calculated,and the detection rates of three image post-processing techniques for different types of rib fracture malunion were compared.Results A total of 243 rib fractures were malunion in 75 patients.The diagnostic sensitivity of VR,MPR and CPR for rib fracture malunion was 52.67%,79.84%and 91.36%,the specificity was 99.58%,97.89%and 99.15%,the accuracy was 83.66%,91.76%and 96.51%,the Youden index was 0.52,0.78 and 0.91,the AUC was 0.761,0.889 and 0.953,respectively.Compared with VR,there were statistically signifi-cant differences in the number of broken rib end misalignment over 1/3,broken rib end overlap,bro-ken rib end angulation and intercostal bridge detected in MPR(P<0.05).Compared with VR,there was a statistically significant difference in the number of different types of rib fracture malunion de-tected by CPR(P<0.05).Compared with MPR,there were statistically significant differences in the number of broken rib end misalignment over 1/3,broken rib end separation and intercostal bridge de-tected in CPR(P<0.05).Conclusion The three image post-processing techniques are of great signifi-cance for the identification of rib fracture malunion.Especially CPR is highly effective in the diagno-sis of rib fracture malunion,and can be used as the main post-processing technique for forensic clini-cal identification of rib fracture malunion.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Patient 1,a 12-day-old female infant,presented with fever,cough,dyspnea,and elevated infection markers,requiring respiratory support.Metagenomic next-generation sequencing(mNGS)of blood and bronchoalveolar lavage fluid revealed Legionella pneumophila(LP),leading to diagnoses of LP pneumonia and LP sepsis.The patient was treated with erythromycin for 15 days and azithromycin for 5 days,resulting in recovery and discharge.Patient 2,an 11-day-old female infant,presented with dyspnea,fever,elevated infection markers,and multiple organ dysfunction,requiring mechanical ventilation.mNGS of blood and cerebrospinal fluid indicated LP,leading to diagnoses of LP pneumonia,LP sepsis,and LP intracranial infection.The patient was treated with erythromycin for 19 days and was discharged after recovery.Neonatal LP pneumonia lacks specific clinical symptoms,and azithromycin is the preferred antimicrobial agent.The use of mNGS can provide early and definitive diagnosis for severe neonatal pneumonia of unknown origin.

This study was aimed at analyzing the changes in the cell proteome of HTR-8/Svneo human villous trophoblasts during infection with Listeria monocytogenes,to explore the mechanisms involved in L.monocytogenes infection of the placenta at the molecular level in host cells.Tandem Mass Tag(TMT)proteomics was used to compare the quantitative proteome be-tween the HTR-8/Svneo infection group and control group.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases were used to analyze enrichment in the molecular functions,biological processes,and metabolic pathways of differentially expressed proteins.A total of 76 285 peptides and 6 979 quantifiable proteins were identified.A total of 356 proteins showed significant differential expression:153 up-regulated and 203 down-regulated.The protein with the high-est fold change was microtubule motor protein(B4DYE2),and the protein with the lowest fold change was translation initia-tion factor 1(Q6IAV3).GO functional enrichment and KEGG metabolic pathway enrichment analyses indicated that the up-regulated proteins were involved primarily in biological processes and metabolic pathways such as the movement of microtubules and microfilament as well as autophagy,whereas the down-regulated proteins were involved mainly in primary metabolic pathways,such as carbon metabolism,nitrogen metabolism,amino acid biosynthesis,and nucleic acid metabolism,as well as ubiquitin mediated protein hydrolysis.In the process of infection of HTR-8/Svneo by L.monocytogenes,the basal metabolism of host cells may be significantly diminished,and the autophagy level may be high.The significant up-regulation of cell migration-inducing and hyaluronan-binding protein CEMIP(Q8WUJ3)suggested an important role of this protein in regulating the migration and invasion of trophoblast cells,thus causing adverse pregnancy outcomes.Our findings may provide new ideas for the study of the molecular mechanism of L.monocytogenes infection of the placenta.

Objective To explore the efficacy and safety of ultrasound-guided radiofrequency ablation combined with foam sclerotherapy in the treatment of primary small saphenous vein varicosities.Methods A total of 46 patients with primary small saphenous vein varicosities in our department from November 2021 to November 2022 were retrospectively analyzed.Depending on the patient's choice of surgical method,they underwent radiofrequency ablation combined with sclerotherapy(observation group,n=23)or high ligation and stripping of the saphenous vein(control group,n=23).The surgical time,intraoperative blood loss,length of hospital stay,postoperative Venous Clinical Severity Score(VCSS),incidence of postoperative complications,treatment satisfaction,and recurrence were compared between the two groups.Results Compared with the control group,the observation group had shorter surgical time[(56.1±6.0)min vs.(81.7±10.6)min,t=-10.128,P=0.000],less intraoperative blood loss[(27.0±4.1)ml vs.(41.4±4.8)ml,t=-11.016,P=0.000],shorter hospitalization time[(2.0±0.7)dvs.(5.6±0.9)d,t=-14.319,P=0.000],lower VCSS scores at 3,6,and 12 months after surgery[(7.4±2.0)points vs.(8.9±2.5)points,t=-2.165,P=0.036;(5.3±1.8)points vs.(6.5±2.2)points,t=-2.149,P=0.037;(2.6±1.3)points vs.(4.0±1.8)points,t=-2.912,P=0.006],higher satisfaction[satisfied,somewhat satisfied,dissatisfied in 18,4,and 1 cases in the observation group and 8,10,and 5 cases in the control group,respectively,Z=-2.967,P=0.003].There were no statistically significant differences in the complication incidence and recurrence rate between the two groups(P＞0.05).Conclusion Ultrasound-guided radiofrequency ablation combined with foam sclerotherapy in the treatment of primary small saphenous vein varicosities is safe and effective.

Objective:To explore the risk factors for duodenal papillary adenocarcinoma by comparing the differences in clinical and endoscopic features between patients with duodenal papillary adenomas and adenocarcinomas.Methods:This study retrospectively included patients diagnosed as having duodenal papillary adenocarcinoma and adenoma from January 1st 2018 to June 1st 2023 at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School. Demographic, clinical manifestations, laboratory tests, imaging, endoscopic and pathological characteristics of patients with adenomas and adenocarcinomas were collected and compared. Multivariable logistic regression analysis was employed to identify high-risk factors for duodenal papillary adenocarcinoma.Results:A total of 119 cases of adenocarcinoma and 171 cases of adenoma were included. There were statistically significant differences between the two groups in terms of patient age, body mass index (BMI), clinical symptoms, family history of malignant tumors, bile duct dilation, pancreatic duct dilation, lesion size, adenoma site classification, stage assessed by EUS, and involvement of the bile and pancreatic ducts ( P<0.05). Univariate logistic regression analysis revealed that non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, involvement of the bile and pancreatic ducts assessed by EUS, age ≥60 years, lesion size ≥1.5 cm, clinical symptoms, family history of malignant tumors, bile duct dilation, and pancreatic duct dilation were risk factors for duodenal papillary adenocarcinoma. Multivariate logistic regression analysis showed that non-ampullary lesions ( OR=7.00, 95% CI:1.44-34.15, P=0.016), involvement not limited to the major duodenal papilla assessed by EUS ( OR=13.77, 95% CI: 4.69-40.45, P<0.001), age ≥60 years ( OR=2.52, 95% CI: 1.23-5.18, P=0.011), bile duct dilation ( OR=2.58, 95% CI: 1.12-5.94, P=0.026), and lesion size ≥1.5 cm ( OR=2.76, 95% CI:1.36-5.59, P=0.005) were independent risk factors for duodenal papillary adenocarcinoma. Conclusion:This study shows the independent risk factors for duodenal papillary adenocarcinoma, which include non-ampullary lesions, involvement not limited to the major duodenal papilla assessed by EUS, age ≥60 years, bile duct dilation, and lesion size ≥1.5 cm.

Aim To investigate the effects of realgar on the proliferation, invasion and ferroptosis of esophageal cancer cells. Methods Different concentrations of realgar(0, 10,20, 40, 60, 80, 100 μmol·L-1)or realgar 1/2IC