BACKGROUND:Dental pulp stem cells,which derived from the dental pulp tissue,are one type of dental-derived mesenchymal stem cells,possess significant properties of self-renewal and multi-lineage differentiation.In recent years,series of researches focus on dental pulp stem cells and their derivatives such as extracellular vesicles,conditioned medium,and decellularized extracellular matrix,those have positive effects on the repair and regeneration of pulp tissue injury,showing an attractive clinical application.OBJECTIVE:To systematically review the researches and applications of dental pulp stem cells and their derivatives in dental pulp tissue engineering.METHODS:Literature searches were conducted in PubMed,China Biology Medicine(CBM),and China National Knowledge Infrastructure(CNKI)databases for articles published from January 2005 to June 2023.The search terms included"dental pulp stem cells,extracellular vesicles,exosomes,apoptotic bodies,conditioned medium,decellularized matrix,regeneration"in Chinese and English.After screening the titles and abstracts,duplicate and irrelevant studies were excluded.Finally,103 studies closely related to dental pulp regeneration were included for review and analysis.RESULTS AND CONCLUSION:Dental pulp stem cells and their derivatives are rich in lots of bioactive factors that can effectively promote odontogenic,angiogenic,and neurogenic differentiation,exhibiting significant potential in the formation of the pulp-dentin complex.However,the clinical translation of dental pulp stem cells and their derivatives still faces several challenges.Future researches should focus on optimizing preparation protocols,elucidating the underlying mechanisms of action,and refining safety assessments to provide novel therapeutic strategies for the repair of dental pulp injury.

BACKGROUND:Dental pulp stem cells,which derived from the dental pulp tissue,are one type of dental-derived mesenchymal stem cells,possess significant properties of self-renewal and multi-lineage differentiation.In recent years,series of researches focus on dental pulp stem cells and their derivatives such as extracellular vesicles,conditioned medium,and decellularized extracellular matrix,those have positive effects on the repair and regeneration of pulp tissue injury,showing an attractive clinical application.OBJECTIVE:To systematically review the researches and applications of dental pulp stem cells and their derivatives in dental pulp tissue engineering.METHODS:Literature searches were conducted in PubMed,China Biology Medicine(CBM),and China National Knowledge Infrastructure(CNKI)databases for articles published from January 2005 to June 2023.The search terms included"dental pulp stem cells,extracellular vesicles,exosomes,apoptotic bodies,conditioned medium,decellularized matrix,regeneration"in Chinese and English.After screening the titles and abstracts,duplicate and irrelevant studies were excluded.Finally,103 studies closely related to dental pulp regeneration were included for review and analysis.RESULTS AND CONCLUSION:Dental pulp stem cells and their derivatives are rich in lots of bioactive factors that can effectively promote odontogenic,angiogenic,and neurogenic differentiation,exhibiting significant potential in the formation of the pulp-dentin complex.However,the clinical translation of dental pulp stem cells and their derivatives still faces several challenges.Future researches should focus on optimizing preparation protocols,elucidating the underlying mechanisms of action,and refining safety assessments to provide novel therapeutic strategies for the repair of dental pulp injury.

Patients with metastatic castration-resistant prostate cancer (mCRPC) face poor prognoses due to tumor heterogeneity and drug resistance. Antibody-drug conjugates (ADCs) have been under development for over two decades for mCRPC treatment. Several clinical trials have demonstrated promising antitumor activity and acceptable safety profiles for ADCs in this setting. Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 and DXC008 (both dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, an international multicenter phase Ⅲ clinical trial (NCT06925737) for mCRPC has been initiated in May 2025 for evaluating B7-H3-targeted ADC ifinatamab deruxtecan. This review summarizes recent advances in ADCs targeting key antigens in mCRPC (including PSMA, B7-H3, STEAP1, TROP2, SLC44A4, and others) and explores combination strategies, offering insights to inform the clinical management of mCRPC.
Humans ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Male ; Immunoconjugates/therapeutic use* ; Glutamate Carboxypeptidase II/immunology* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; B7 Antigens/immunology* ; Neoplasm Metastasis ; Prostate-Specific Antigen ; Antigens, Neoplasm/immunology* ; Antigens, Surface ; Camptothecin/analogs & derivatives* ; Oxidoreductases

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To explore the feasibility of anastomosis between bladder and intestine of experimental rabbit by drag anastomosis.Methods:In this study 40 Japanese big-eared rabbits were randomly divided into two groups through random number table, the experimental group and the control group, each group with 20 rabbits. In the experimental group, the bladder neck was fixed to the catheter and then the catheter was drawn outward. With the traction of the catheter, the bladder neck was anastomosed with the distal intestinal tube by means of suture free. The control group was anastomosed by regular interrupted suture of bladder and intestine. The operation time, anastomosis time, intraoperative blood loss, postoperative urinary leakage rate and postoperative anastomotic healing of rabbits in the two groups were compared.Results:The operation time of the experimental group was shorter than that of the traditional interrupted suture anastomosis group [(33.26±2.79)min vs. (35.25±1.83)min, P=0.014]. The anastomosis time of the experimental group was significantly shorter than that of the traditional interrupted suture anastomosis group[(7.55±1.2)min vs. (8.65±1.03 min), P=0.005]. The intraoperative blood loss in the experimental group was similar to that in the control group[(6.47±2.41) ml vs. (6.75±1.83) ml, P=0.691]. The event of contrast media extravasation occurred in 2 of the 10 experimental rabbits after receiving cystography in the experimental group, and the urinary leakage rate was 20%(2/10). In the control group, contrast media extravasation occurred in 1 of the 9 experimental rabbits after receiving cystography, and the urinary leakage rate was 11.1%(1/9), and the difference of the two groups was not statistically significant ( P=0.348). Anastomotic healing score was (2.0±0.7) in the experimental group, and (2.1±0.74) in the control group ( P=0.767). Conclusions:The bladder-intestine drag-and-bond anastomosis technique, with significantly shorter anastomosis time, was feasible, easy and convenient. Our research provides an experimental and theoretical basis for the clinical application of drag-and-bond anastomosis technique in clinic.

Objective:To summarize the best evidence for early enteral nutrition support in postoperative patients with gastric cancer and evaluate its effectiveness.Methods:From March to August 2021, 108 postoperative patients with gastric cancer admitted to the Gastrointestinal Surgery of the First Affiliated Hospital of Ningbo University were selected. We applied evidence-based nursing methods to summarize the best evidence for early enteral nutrition support in postoperative gastric cancer patients, and constructed and implemented the best evidence application strategy through baseline review, evaluation of evidence application clinical scenarios and barriers. We compared the various indicators of two groups of patients before the application of evidence (March to May 2021, n=55) and after the application of evidence (June to August 2021, n=53) . Results:No adverse events occurred during the application of evidence. After applying evidence, the correct nutritional assessment rate increased from 41.82% (23/55) at baseline review to 90.57% (48/53), the implementation rate of early postoperative enteral nutrition increased from 0 to 45.28% (24/53), the start time of postoperative enteral nutrition shortened from (3.75±2.33) days to (2.06±1.38) days, and the implementation rate of postoperative priority oral nutrition increased from 63.64% (35/55) to 86.79% (46/53), nutritional related complications decreased from 40.00% (22/55) to 20.75% (11/53), and the differences were all statistically significant ( P<0.05) . Conclusions:The application of the best evidence for early enteral nutrition support in postoperative gastric cancer patients can shorten the start time of postoperative enteral nutrition, reduce postoperative nutrition related complications, and promote early recovery of patients.

OBJECTIVE： To study the effect mechanism of iridoid glycosides extracted from Scrophularia ningpoensis inhibiting cardiomyocytes apoptosis in myocardial infarction model rats. METHODS： The male Wistar rats were randomly divided into sham operation group， model group and S. ningpoensis iridoid glycosides low-dose， medium-dose and high-dose groups， with 10 rats in each group. Myocardial infarction models were established by ligating the left anterior descending coronary artery of the rats， and sham operation group was only threaded without ligation. After the model was established， each administration group was given S. ningpoensis iridoid glycosides suspension intragastrically at three different doses of 50，100，200 mg/kg （by the amount of total glycosides extract） with 10 mL/time， twice a day， for consecutive 7 days. Sham operation group and model group were given constant volume of normal saline intragastrically with same method. The changes of S-T segment of lead ECG Ⅱ were recorded before， after and during 7 days of administration. Cardiac function of rats was examined. The serum levels of LDH， CK-MB， cTnⅠ， NT-pro BNP and TNF-α were determined by colorimetry， immunosuppression or ELISA. The apoptosis of myocardial cells was observed by TUNEL method. SOD activity and MDA content in cardiac myocytes were detected by colorimetry. The expressions of Bcl-2， Bax， Cyt C， Caspase-8， Caspase-9， Caspase-12， Caspase-3 and Calpain in cardiac myocytes were detected by ELISA， enzymolysis colorimetry or enzymatic fluorescence assay. RESULTS： Compared with sham operation， electrocardiogram S-T segment was significantly elevated and the left ventricular end-diastolic diameter and left ventricular end-systolic diameter were significantly increased in the model group； left ventricular ejection fraction and short axis shortening rate decreased significantly； serum levels of LDH， CK-MB， cTnⅠ， NT-pro BNP and TNF-α were increased significantly； there were a large number of yellow-brown apoptotic cells in myocardial tissue； the activity of SOD in myocardial tissue was significantly decreased while the content of MDA was significantly increased； the protein expression level of Bcl-2 and Bcl-2/Bax were significantly decreased， while the levels of Bax， Cyt C， Caspase-3， Caspase-8， Caspase-9， Caspase-12 and Calpain were significantly increased （P＜0.05 or P＜0.01）. Compared with model group， above indexes and pathological changes of myocardial tissue were improved significantly in administration group； the level of Bcl-2 and Bcl-2/Bax in cardiomyocytes increased significantly， while the levels of Bax， Cyt C， Caspase-3， Caspase-8， Caspase-9， Caspase-12 and Calpain decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： S. ningpoensis iridoid glycosides can inhibit the activation of Caspase-3 by inhibiting three apoptotic pathways related to Caspase-8， Caspase-9 and Caspase-12， and then inhibit the apoptosis of cardiomyocytes.

Objective To investigate the serum γ-glutamyl transferase(γ-GT)level and its clinical significances in hepatitis B virus(HBV)-liver failure(LF)patients.Methods γ-GT levels were detected in 89 LF patients,30 cases with cirrhosis and 30 healthy controls.Difference of serum γ-GT between survival group and death group in LF patients and dynamics of γ-GT after hospitalization were studied. Survival rate between γ-GT increase group and decrease group were compared.The associations of γ-GT with model for end stage live disease(MELD)and prealbumin were calculated.Results At baseline,the γ-GT levels in LF,cirrhosis and healthy control groups were(149.61 ± 69.86),(123.96 ± 59.52)and (48.28 ± 10.25)U/L,respectively,the difference among groups was significant(F= 178.150,P<0.05).The survival group in LF patients showed significant increase of γ-GT one week after hospitalization compared with death group([75.27 ± 10.34]vs[29.47 ± 5.05],t=5.40,P<0.05). The γ-GT increase group showed higher survival rate than γ-GT decrease group[76.19%(48/63)vs 23.08%[6/26],χ2=21.76,P<0.05].Serum γ-GT level in LF patients was positively correlated with both MELD score and prealbumin(r=0.709 and -0.627,respectively,both P<0.05).Conclusions The rise of γ-GT may indicate a better prognosis in LF patients.Serum γ-GT positively correlates with prealbumin and both could reflect the regeneration of hepatocytes.

Objective: To summarize the preliminary experience with transoral endoscopic thyroidectomy via vestibular approach (TOETVA). Methods: A total of 150 consecutive patients with thyroid disease underwent TOETVA from November 2014 to February 2017 at Department of Thyroid Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine. The patients were comprised of 138 females and 12 males. The mean age of the patients was (31.7±7.6) years (ranging from 15 to 51 years). There were 108 patients of differential thyroid carcinoma (T1 or T2 ≤3 cm, cN0 or cN1a, M0) and 42 patients of benign thyroid disease (solid nodule ≤6 cm). The criteria analyzed were clinicopathologic characteristics, types of operation, operation time, complications and results of follow-up. Results: Two cases were converted into open surgery due to an incredible unexpected tumor size and tracheal invasion, respectively. One hundred and three patients with papillary carcinoma underwent transoral central neck dissection (CND), with the mean operation time of (146±34) minutes for hemithyroidectomy with CND, and (187±36) minutes for total or near total thyroidectomy with CND. The mean number of lymph node yields was 8.2±4.7, and the lymph node metastasis rate was 41.7% (43/103). Regarding postoperative complications, transient hoarseness occurred in 3 patients, and permanent recurrent laryngeal nerve occurred in 2 patients. One patient had local infection or transient mental nerve palsy. Transient hypocalcemia occurred in 31.8% of 22 patients who underwent total, near-total, or subtotalthyroidectomy, and no permanent hypocalcemia was registered. Mean hospital stay after operation was (3.5±0.6) days (ranging from 2 to 5 days). Mean follow-up period was (11.5±7.8) months (ranging from 1 to 28 months), no recurrence or metastasis occurred. Conclusions TOETVA is feasible and safe for strictly selective patients. It brings perfect cosmetic effect. Long-term follow-up and further study is needed to assess its curative effect.