Objective To prepare a thermosensitive hydrogel scaffold loaded with bone marrow mesenchymal stem cells（BMSCs） and resveratrol liposomes （RSV-LIP） to form a therapeutic unit and evaluate its treatment efficacy for traumatic brain injury （TBI）. Methods BMSCs were extracted from rats, and RSV-LIP was prepared and characterized. Cell models were constructed to investigate the pharmacological effects of BMSCs combined with RSV-LIP. BMSCs and RSV-LIP were then loaded into the hydrogel, and a TBI mouse model was established to evaluate the therapeutic effects of the hydrogel. Results The RSV-LIP had a particle size of 127.8 nm, a Zeta potential of −4.9 mV, an encapsulation efficiency of 78.50%, and a drug loading content of 2.37%. Live-dead staining indicated good biocompatibility of the hydrogel. The combination of BMSCs and RSV-LIP significantly inhibited TNF-α and reduced ROS levels, promoting cell migration in scratch assays. Compared to the control group, the hydrogel group showed significantly lower mNSS scores （P<0.01）, higher hanging scores （P<0.001）, and reduced stepping errors （P<0.001）. Conclusion The combination of BMSCs and RSV-LIP exhibited antioxidative stress, anti-inflammatory, and neurogenic cell migration-promoting effects. When loaded into a hydrogel scaffold and locally implanted, it could improve the motor and sensory functions in TBI mice.

Objective: To investigate the clinical efficacy and safety of pudendal nerve modulation (PNM) in the treatment of female pudendal neuralgia (PN)，so as to promote the clinical application of this technique. Methods: A retrospective analysis was conducted on 20 female PN patients who failed conservative treatment at Gongli Hospital during Nov.2020 and Oct.2023.All patients underwent simultaneous PNM and sacral nerve modulation (SNM) with the assistance of 3D printing navigation.Dual-stage test electrodes for PNM and SNM were implanted，followed by alternate therapeutic trial for each modality.Secondary conversion rates and longitudinal outcomes，including visual analogue score (VAS)，patient health questionnaire-9 (PHQ-9)，and quality of life (QoL) scores were compared preoperatively，post-stage Ⅰ，and at 3，6，and 12 months post-stage Ⅱ. Results: All operations were successful.After the trial phase，the secondary conversion rate for PNM was significantly higher than that for SNM; 16 patients (16/20，80%) chose the second-phase PNM implantation surgery，3 (3/20，15%) chose second-phase SNM implantation，and 1 (1/20，5%) had electrodes removed due to ineffective results from both trials.Further assessment revealed that the improvements in VAS，PHQ-9，and QoL scores for PNM patients were significantly better than those for SNM patients after the first phase of surgery and at 3，6 and 12 months after the second-phase conversion (P<0.05).No complications such as electrode migration or infection were observed during the follow-up of 12-15 months. Conclusion: PNM provides more effective relief of pain symptoms and improvements in depressive states for female PN patients compared to SNM.With the assistance of 3D printing navigation，the operation is simple and safe，and offers stable therapeutic effects.It is worthy of clinical promotion and application.

BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but there are still many patients who suffer tumor recurrence. However, valuable predictors of treatment outcomes remain limited. This study aimed to assess the value of the serum immune biomarkers to predict the prognosis. METHODS: We reviewed cervical cancer patients treated with CCRT between January 2014 and May 2018 at Peking Union Medical College Hospital. The systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and lactate dehydrogenase (LDH) were calculated using blood samples. The relationship between immune markers and the treatment outcome was analyzed. The area under the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency. The Cox proportional hazards model and log-rank were used to predict overall survival (OS) and disease-free survival (DFS). RESULTS: This study included 667 patients. Among them, 195 (29.2%) patients were defined as treatment failure, including 127 (19.0%) patients with pelvic failure, 94 (14.1%) distant failure, and 25 (3.7%) concurrent pelvic and distant failure. It revealed that the tumor stage, size, metastatic lymph nodes (MLNs), and serum immune biomarkers, such as SII, SIRI, and LDH, were significantly related to treatment outcomes. We demonstrated that the optimal cut-off of the SII, SIRI, and LDH were 970.4 × 10 9 /L, 1.3 × 10 9 /L, and 207.52 U/L, respectively. Importantly, this study presented that LDH level had the highest OR (OR = 4.2; 95% CI [2.3-10.8]). Furthermore, the OS and DFS for patients with pre-SII ≥970.5 × 10 9 /L were significantly worse than those with pre-SII <970.5 × 10 9 /L. Similarly, pre-SIRI ≥1.25 × 10 9 /L and pre-LDH ≥207.5 U/L were related to poor survival outcomes. CONCLUSIONS This study demonstrated that the baseline SII, SIRI, and LDH levels can be used to accurately and effectively predict the treatment outcomes after CCRT and long-term prognosis. Our results may offer additional prognostic information in clinical, which helps to detect the potential recurrent metastasis in time.
Humans ; Female ; Uterine Cervical Neoplasms/drug therapy* ; Middle Aged ; Adult ; Aged ; Chemoradiotherapy/methods* ; L-Lactate Dehydrogenase/blood* ; Treatment Outcome ; Disease-Free Survival ; Prognosis ; ROC Curve ; Biomarkers, Tumor/blood* ; Proportional Hazards Models

Tumors are complex, highly heterogeneous diseases that place an enormous burden on the world's healthcare systems. Updating understanding of tumor initiation and progression is critical and the current breakthrough lies in cancer neuroscience, which focuses on the crosstalk between neural components and tumors. Neuropeptides are a class of highly potent peptides, that perform the physiological functions of neurotransmitters, neuromodulators, and endocrine hormones. Currently, many studies have shown that many cellular components of the tumor microenvironment express neuropeptides and their receptors and that neuropeptides may play an important role in their cellular communication. In addition, neuropeptides and their receptors affect cancer hallmarks such as proliferation, invasion and metastasis, angiogenesis, immune escape, metabolic reprogramming, and others. More importantly, neuropeptides may also affect some tumor comorbidities such as insomnia, depression, anorexia, cancer pain, and others. Targeting neuropeptides in combination with new therapeutic strategies may significantly advance anti-tumor therapy, not only for treating the tumor itself but also for improving the patient's quality of life.

OBJECTIVES: To investigate the effect of needle knife release on median nerve (MN) and transverse carpal ligament (TCL) morphology and function and expression levels of inflammatory factors in rabbit models of carpal tunnel syndrome (CTS). Methods Thirty adult New Zealand rabbits were randomized equally into control group, CTS model group, ultrasound-guided needle knife release group, needle knife release group without ultrasound guidance, and sham treatment groups. In all but the control group, the rabbits were subjected to CTS modeling by 10% glucose solution injection into the carpal tunnel once a week for 4 consecutive weeks, followed by interventions with a single treatment session. At 3 days and 30 days after the interventions, 3 rabbits from each group were selected for ultrasound measurement of TCL and MN thickness, electrophysiological testing, ultrasound elastography, and inflammatory cytokine level assessment. RESULTS: In the rabbit models of CTS, ultrasound-guided needle knife release significantly reduced the thickness of TCL and MN and improved sensory nerve conduction velocity at both 3 and 30 days after the intervention. Elastography of the TCL showed markedly softened intra-carpal tissues after ultrasound-guided needle knife release and achieved superior outcomes over those in the other groups. The treatment also significantly reduced IL-17 levels and lowered IL-6 and PGE2 expression at 30 days after the intervention. CONCLUSIONS Needle knife release of the TCL reduces thickness of the MN and TCL, enhances median nerve function, alleviates intrascatic tissue stiffness, and downregulates inflammatory factors in the carpal tunnel in rabbit models of CTS, and ultrasound guidance further enhances its therapeutic efficacy.
Animals ; Rabbits ; Carpal Tunnel Syndrome/surgery* ; Median Nerve/physiopathology* ; Disease Models, Animal

OBJECTIVES: The mechanism of the odontogenic differentiation of apical papillary cells (APCs) stimulated by bioactive glass 45S5 is still unclear. This study aims to investigate the effect of autophagy on the odontogenic differentiation of APCs stimulated by bioactive glass 45S5. METHODS: APCs were isolated and cultured in vitro, and the cell origin was identified by flow cytometry. The culture medium was prepared with 1 mg/mL 45S5, and its pH and ion concentration were determined. The experiments were divided into control, 45S5, and 3-methyladenine (3-MA) 45S5 groups. In the 45S5 group, APCs were induced to culture with 1 mg/mL 45S5. In the 3-MA 45S5 group, the autophagy inhibitor 3-MA was added to 1 mg/mL 45S5. Protein immunoblotting assay (Western blot) was used to detect the expression of autophagy-associated proteins of microtubule-associated protein 1 light-chain 3β (LC3B) and P62 after 24 h of induction culture in each group. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of bone sialoprotein (BSP), Runt-related transcription factor 2 (Runx2), dentin sialophosphoprotein (DSPP), and dentin matrix protein-1 (DMP-1) after 7 d of induction culture. Cellular alkaline phosphatase (ALP) staining analyzed cellular ALP activity at 7 d of induction, and alizarin red staining evaluated the formation of mineralized nodules at 21 d of induction. RESULTS: The pH of the 45S5 extract culture medium was 8.65±0.01, which was not significantly different from that of the control group (P>0.05). The silicon ion concentration of the 45S5 induction culture medium was (1.56±0.07) mmol/L, which was higher than that of the control group (0.08±0.01) mmol/L (P<0.05). The calcium ion concentration of the 45S5 induction culture was (1.57±0.15) mmol/L, which was not significantly different from that of the control group (P>0.05). Western blot results showed that LC3B-Ⅱ/Ⅰ ratio increased and P62 expression decreased in the 45S5 group compared with those in the control group (P<0.05). By contrast, the ratio decreased and the expression increased in the 3-MA 45S5 group compared with those in the 45S5 group (P<0.05). RT-qPCR results showed that the expression of BSP, Runx2, DMP-1, and DSPP enhanced in the 45S5 group compared with that in the control group (P<0.05), but the expression decreased in the 3-MA 45S5 group compared with that in the 45S5 group (P<0.05). Semi-quantitative analysis of ALP staining and alizarin red staining showed that the ALP activity was enhanced, and the formation mineralized nodule increased in the 45S5 group compared with those in the control group. The ALP activity weakened, and the formation mineralized nodules were reduced in the 3-MA 45S5 group compared with that those in the 45S5 group. CONCLUSIONS Cell autophagy participates in the odontogenic differentiation of APCs induced by 1 mg/mL 45S5 in vitro.
Autophagy/drug effects* ; Cell Differentiation/drug effects* ; Odontogenesis/drug effects* ; Dental Papilla/cytology* ; Humans ; Microtubule-Associated Proteins/metabolism* ; Glass/chemistry* ; Cells, Cultured ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Extracellular Matrix Proteins/metabolism* ; Ceramics/pharmacology* ; Adenine/pharmacology* ; Sialoglycoproteins/metabolism* ; Phosphoproteins/metabolism* ; Integrin-Binding Sialoprotein/metabolism* ; Alkaline Phosphatase/metabolism* ; RNA-Binding Proteins

Objective To investigate the clinical efficacy of platelet-rich plasma (PRP) therapy for interstitial cystitis/bladder pain syndrome (IC/BPS). Methods This single-center prospective study involved 97 IC/BPS patients treated in our hospital during Sep.2023 and Apr.2025, who underwent transurethral bladder injection of PRP. The injections were administered once a month for four sessions. The global response assessment (GRA) score,24-hour urinary frequency, maximum single voiding volume, visual analogue scale (VAS) score, O'Leary score, pelvic pain, urgency and frequency (PUF) score, and Zung self-rating anxiety scale (SAS) score were analyzed. Results All 97 patients completed four injections. The GRA score,24-hour urinary frequency, VAS score, O'Leary score and PUF score were improved significantly after treatment (P<0.007). Intraoperative bladder capacity with significant improvement were observed after the first injection (P<0.01), and the maximum urine output were observed after the fourth injection (P<0.007). The SAS score was not significantly improved. Conclusion Repeated PRP injections can effectively alleviate bladder pain, improve frequent and urgent urination symptoms, and increase the bladder capacity.

Objective:To evaluate the characteristics, clinical management and clinical outcomes of type 2 intestinal failure (IF).Methods:A descriptive case-control study was carried out. The inclusion criteria were as follows: (1) the diagnosis of IF was performed according to the European Society for Parenteral and Enteral Nutrition (ESPEN) consensus statement. (2) using a requirement for parenteral nutrition (PN) of 28 days or more as surrogate marker. (3) a multidisciplinary team (MDT) included surgeons, nutritionist, pharmacist, stoma therapists, and critical care physicians. (4) complete laboratory data. Patients with type 1 and type 3 IF and those who do not cooperate with follow-up. All the data of 67 type II IF were collected from the database in Sir Run Run Shaw Hospital from Jan 2016 to Dec 2023. The pathophysiology, clinical management, and outcomes of type II IF were analyzed.Results:A total of 67 type II IF were included. The median age was 54 (15-83) with 43 males and 24 females. The body mass index was (17.5±3.8) kg/m 2, the incidence of malnutrition was 67.2% (45/67), the incidence of sarcopenia was 74.6% (50/67), the median number of previous surgeries was 2.0 (1-13), and the median duration time of PN was 2.1 (1-12) months. The underlying disease of type 2 IF included 36 Crohn`s disease, 2 ulcerative colitis, 3 radiation enteritis, 2 intestinal Behcet's disease, 4 mesenteric infarction, 1 aggressive fibromatosis, 5 abdominal cocoon syndrome, 5 gastrointestinal perforation, 1 hernia, 4 intestinal dysmotility, and 4 other reasons (gastrointestinal tumor, trauma, and non-Hodgkin's lymphoma). According to the pathophysiology of IF, there were 33 intestinal fistula, 12 intestinal dysmotility, 6 mechanical obstruction, 13 short bowel syndrome, and 3 extensive small bowel mucosal disease. After treatment with MDT, 67 patients with type 2 IF received nutritional support therapy for intestinal rehabilitation treatment, of which 36 patients recovered with oral diet or enteral nutrition, 31 patients underwent reconstructive surgery after intestinal rehabilitation treatment failure. The median duration time of reconstructive surgery was 2.7 (1-9) months. 24 patients recovered intestinal autonomy after surgery, with 7 deaths, including 6 deaths due to abdominal infections and 1 case of intestinal dysmotility with abiotrophy and liver failure. Conclusion:Standardized multidisciplinary treatment plays an important role in type II intestinal failure, and it promotes patients with intestinal failure regain enteral autonomy.

Objective:To evaluate the characteristics, clinical management and clinical outcomes of type 2 intestinal failure (IF).Methods:A descriptive case-control study was carried out. The inclusion criteria were as follows: (1) the diagnosis of IF was performed according to the European Society for Parenteral and Enteral Nutrition (ESPEN) consensus statement. (2) using a requirement for parenteral nutrition (PN) of 28 days or more as surrogate marker. (3) a multidisciplinary team (MDT) included surgeons, nutritionist, pharmacist, stoma therapists, and critical care physicians. (4) complete laboratory data. Patients with type 1 and type 3 IF and those who do not cooperate with follow-up. All the data of 67 type II IF were collected from the database in Sir Run Run Shaw Hospital from Jan 2016 to Dec 2023. The pathophysiology, clinical management, and outcomes of type II IF were analyzed.Results:A total of 67 type II IF were included. The median age was 54 (15-83) with 43 males and 24 females. The body mass index was (17.5±3.8) kg/m 2, the incidence of malnutrition was 67.2% (45/67), the incidence of sarcopenia was 74.6% (50/67), the median number of previous surgeries was 2.0 (1-13), and the median duration time of PN was 2.1 (1-12) months. The underlying disease of type 2 IF included 36 Crohn`s disease, 2 ulcerative colitis, 3 radiation enteritis, 2 intestinal Behcet's disease, 4 mesenteric infarction, 1 aggressive fibromatosis, 5 abdominal cocoon syndrome, 5 gastrointestinal perforation, 1 hernia, 4 intestinal dysmotility, and 4 other reasons (gastrointestinal tumor, trauma, and non-Hodgkin's lymphoma). According to the pathophysiology of IF, there were 33 intestinal fistula, 12 intestinal dysmotility, 6 mechanical obstruction, 13 short bowel syndrome, and 3 extensive small bowel mucosal disease. After treatment with MDT, 67 patients with type 2 IF received nutritional support therapy for intestinal rehabilitation treatment, of which 36 patients recovered with oral diet or enteral nutrition, 31 patients underwent reconstructive surgery after intestinal rehabilitation treatment failure. The median duration time of reconstructive surgery was 2.7 (1-9) months. 24 patients recovered intestinal autonomy after surgery, with 7 deaths, including 6 deaths due to abdominal infections and 1 case of intestinal dysmotility with abiotrophy and liver failure. Conclusion:Standardized multidisciplinary treatment plays an important role in type II intestinal failure, and it promotes patients with intestinal failure regain enteral autonomy.

Objective To assess the efficacy of pirfenidone combined with PD-L1 inhibitor for treatment of bladder cancer in a mouse model and its effect on tumor immune microenvironment modulation.Methods Forty C57BL/6 mouse models bearing ectopic human bladder cancer xenografts were randomized into control group,PD-L1 inhibitor group,pirfenidone group and combined treatment group(n=10).After successful modeling,PD-L1 inhibitor treatment was administered via intraperitoneal injection at 12.5 mg/kg every 3 days,and oral pirfenidone(500 mg/kg)was given on a daily basis.The survival rate of the mice and tumor growth rate were compared among the 4 groups.The expressions of CD3,CD8,CD45,E-cadherin and N-cadherin in the tumor tissues were detected with immunohistochemistry after the 21-day treatment,and bone marrow-derived suppressor cells(MDSCs)were observed with immunofluorescence staining;serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),urea nitrogen(BUN),creatinine(CRE)and lactate dehydrogenase(LDH-L)were analyzed using an automated biochemical analyzer.Results Treatment with PD-L1 inhibitor and pirfenidone alone both significantly decreased tumor growth rate and tumor volume at 21 days(P<0.05),but the combined treatment produced an obviously stronger inhibitory effect(P<0.05).PD-L1 inhibitor and pirfenidone alone significantly increased E-cadherin expression and decreased N-cadherin expression in the tumor tissue(P<0.05).The two treatments both significantly increased the percentage of CD3+,CD8 and CD45+ T cells and decreased the percentage of Ly-6G+CD11b+MDSCs in the tumor tissue,and these changes were more obvious in the combined treatment group(P<0.05).No significant differences were found in serum ALT,AST,BUN,CRE or LDH-L levels among the 4 groups(P>0.05).Conclusion Combined treatment with pirfenidone and PD-L1 inhibitor significantly inhibits the progression of bladder cancer in mice possibly by regulating tumor immune microenvironment and inhibiting epithelial-mesenchymal transition of the tumor cells.