Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.

This case report describes a 68-year-old male patient diagnosed with primary hepatocellular carcinoma (HCC). After receiving Yttrium-90 microsphere selective internal radiation therapy (⁹⁰Y-SIRT), the tumor significantly reduced in size, and tumor markers alpha fetoprotein (AFP) and abnormal prothrombin (PIVKA-Ⅱ) decreased. Postoperative pathological results showed minimal residual tumor cells, indicating that ⁹⁰Y-SIRT has good efficacy and safety in downstaging and conversion of HCC, thereby facilitating subsequent surgical resection.

OBJECTIVE: To explore, identify, and develop novel blood-based indicators using machine learning algorithms for accurate preoperative assessment and effective prediction of postoperative complication risks in patients with rheumatoid arthritis (RA) undergoing total knee arthroplasty (TKA). METHODS: A retrospective cohort study was conducted including RA patients who underwent unilateral TKA between January 2019 and December 2024. Inpatient and 30-day postoperative outpatient follow-up data were collected. Six machine learning algorithms, including decision tree, random forest, logistic regression, support vector machine, extreme gradient boosting, and light gradient boosting machine, were used to construct predictive models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), F1-score, accuracy, precision, and recall. SHapley Additive exPlanations (SHAP) values were employed to interpret and rank the importance of individual variables. RESULTS: According to the inclusion criteria, a total of 1 548 patients were enrolled. Ultimately, 18 preoperative indicators were identified as effective predictive features, and 8 postoperative complications were defined as prediction labels for inclusion in the study. Within 30 days after surgery, 453 patients (29.2%) developed one or more complications. Considering overall accuracy, precision, recall, and F1-score, the random forest model [AUC=0.930, 95% CI (0.910, 0.950)] and the extreme gradient boosting model [AUC=0.909, 95% CI (0.880, 0.938)] demonstrated the best predictive performance. SHAP analysis revealed that anti-cyclic citrullinated peptide antibody, C-reactive protein, rheumatoid factor, interleukin-6, body mass index, age, and smoking status made significant contributions to the overall prediction of postoperative complications. CONCLUSION Machine learning-based models enable accurate prediction of postoperative complication risks among RA patients undergoing TKA. Inflammatory and immune-related blood biomarkers, such as anti-cyclic citrullinated peptide antibody, C-reactive protein, and rheumatoid factor, interleukin-6, play key predictive roles, highlighting their potential value in perioperative risk stratification and individualized management.
Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Arthritis, Rheumatoid/blood* ; Machine Learning ; Postoperative Complications/blood* ; Female ; Male ; Retrospective Studies ; Middle Aged ; Aged ; Risk Factors ; Preoperative Period ; C-Reactive Protein/analysis* ; Risk Assessment

OBJECTIVE: To compare the effects of different concentrations of ropivacaine femoral nerve block on postoperative pain and early exercise fllowing total knee arthroplasty(TKA). METHODS: A total of 90 patients who underwent primary TKA between September 2022 and February 2023 were consecutively enrolled in this study. The cohort consisted of 34 males and 56 females, with a mean age of (66.66±7.03) years old. According to different concentrations of ropivacaine, patients were divided into 0.1% group, 0.2% group and 0.4% group, with 30 patients in each group. The age, gender, body mass index(BMI), American Society of Aneshesiologists(ASA) grade, operation time, anesthesia time, tourniquet using time, Post Anesthesia care unit(PACU) stay duration, ambulation time, first reaching to Bromage 0 grade time, visual analogue scale(VAS), hospitalization period and postoperative adverse reactions were compared among the three groups. RESULTS: All 90 patients were followed up for an average of (31.56±5.62) days, and no postoperative adverse reactions occurred. There were no significant differences among the three groups in terms of age, gender, BMI, ASA classification, operation time, anesthesia time, tourniquet application time, PACU stay duration, and hospitalization period (P>0.05). Significant differences were observed in VAS scores at 1, 2, 4, 6, and 12 hours post-operation among the three groups (P<0.05). Additionally, significant variations were noted in ambulation time and the first reaching to Bromage level 0 time among the three groups (P<0.05). In terms of postoperative pain, the VAS of the 0.1% group at 1, 2, 4, 6, and 12 hours after surgery(1.93±0.52), (2.57±0.77), (3.10±0.71), (3.10±0.71), (3.07±0.45) points were higher than those of the 0.4% group (1.57±0.50), (2.10±0.55), (2.23±0.57), (2.47±0.73), (2.50±0.57) points, and the differences were statistically significant (P<0.05);the VAS of the 0.1% group at 4, 6, and 12 hours after surgery were higher than those of the 0.2% group (2.43±0.57), (2.53±0.57), (2.63±0.56) points, and the differences were statistically significant (P<0.05);there was no statistically significant difference in VAS between the 0.2% group and the 0.4% group (P>0.05). In terms of early postoperative mobility, the time to ambulation time (8.30±2.76) h and the time to achieve the first Bromage grade 0 (6.13±2.18) h were significantly prolonged in the 0.4% group compared to both the 0.1% group (6.93±1.76) h, (4.17±1.18) h and the 0.2% group (6.53±1.59) h, (4.87±1.53) h. No statistically significant differences were observed between the 0.1% and 0.2% groups (P>0.05). CONCLUSION 0.2% ropivacaine femoral nerve block can effectively reduce postoperative pain after TKA and can perform early exercise earlier.
Humans ; Male ; Female ; Ropivacaine/administration & dosage* ; Arthroplasty, Replacement, Knee/adverse effects* ; Aged ; Nerve Block/methods* ; Femoral Nerve/drug effects* ; Middle Aged ; Pain, Postoperative/drug therapy* ; Anesthetics, Local/administration & dosage* ; Amides

OBJECTIVE: To explore clinical efficacy of membrane-induced technique combined with gastrocnemius muscle flap transposition in treating traumatic osteomyelitis of the upper tibia. METHODS: A retrospective analysis was conducted on 7 patients with traumatic osteomyelitis of the upper tibia who were treated with membrane-induced technique combined with gastrocnemius muscle flap transposition from January 2022 to December 2023. Among them, there were 4 males and 3 females; aged from 29 to 57 years old; 4 patients were treated after open fracture, 2 patients were treated after closed fracture, and 1 patient was treated after scalding; the courses of disease ranges from 2 weeks to 8 years; sinus tracts were present in all patients, and the lesion range of the tibia ranged from 5 to 9 cm. The results of deep tissue bacterial culture showed that 2 patients were negative, 3 patients were staphylococcus aureus, 1 patient was methicillin-resistant staphylococcus aureus, and 1 patient was pseudomonas aeruginosa and 1 patient was klebsiella pneumoniae. After debridement, the range of bone defect ranged from 8 to 12 cm, and the cortical defect accounted for approximately 30% of the circumference. The area of soft tissue defect ranged from 8.0 cm×2.0 cm to 10.0 cm×6.0 cm. At the first stage, vancomycin-loaded/meropenem/gentamicin-loaded bone cement was implanted. The gastrocnemius muscle flap was repositioned to cover the wound surface and free skin grafting was performed. After an interval of 7 to 10 weeks, the stageⅡsurgery was performed to remove bone cement. Autologous iliac bone mixed with vancomycin/gentamicin and calcium sulfate artificial bone was transplanted, and the wound was sutured. One patient retained the original internal plants, one patient removed the internal plants and replaced them with steel plate external fixation, one patient replaced the internal plants and added steel plate external fixation, and three patients were simply fixed with steel plate external fixation. One year after operation, the recovery of knee joint and ankle joint functions was evaluated by using Hospital for Special Surgery (HSS) knee joint score and Kofoed ankle joint function score respectively. RESULTS: All patients had their wounds closed simultaneously with bone cement implantation and healed well. All patients were followed up for 12 to 17 months after operation, and satisfactory bone healing was achieved at 6 months after stageⅡsurgery. Twelve months after operation, all patients had good bone healing without obvious limping was observed when walking. At 12 months after operation HSS knee joint score ranged from 93 to 100 points, and Kofoed ankle function score ranged from 96 to 100 points. CONCLUSION For traumatic osteomyelitis of the upper tibia, a staged treatment plan combining membrane-induced technique and gastrocnemius flap transposition on the basis of thorough debridement could safely cover the wound surface, effectively control bone infection and achieve satisfactory bone healing, without adverse effects on limb function.
Humans ; Male ; Female ; Middle Aged ; Osteomyelitis/surgery* ; Adult ; Surgical Flaps ; Retrospective Studies ; Tibia/injuries* ; Muscle, Skeletal/surgery*

OBJECTIVE: To investigate the effect and mechanism of Shuangshi Tonglin Capsules (SSTL) in the treatment of prostate fibrosis (PF). METHODS: Human prostate stromal cells (WPMY-1) were used for in vitro experiments to establish PF cell models induced with estradiol (E₂). The cell proliferation, migration and clonogenic capacity were determined by cell counting kit-8, scratch assay, and crystal violet staining, respectively. Sprague-Dawley rats were used for in vivo experiments. The changes in histomorphology and organ index of rat prostate by SSTL were determined. Pathologic changes and collagen deposition changes in rat prostate were observed by haematoxylin and eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay kits were used to determine changes in rat PF markers fibroblast growth factor-23 (FGF-23), E₂ and prostate specific antigen (PSA). Mechanistically, changes in oxidative stress indicators by SSTL were determined in WPMY-1 cells and PF rats. Then the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins as well as Nrf2 and TGF-β1 mRNA were further detected by Western blot or quantitative real-time polymerase chain reaction both in vivo and in vitro. RESULTS: In the efficacy study, SSTL significantly reduced the proliferation, migration, and clonogenic ability of cells, improved the morphology of the glandular tissue, significantly reduced the prostate index, reduced glandular fibrous tissue and collagen deposition, and resulted in a significant decrease in the levels of FGF-23, E₂ and PSA (P<0.01 or P<0.05). In the mechanistic study, SSTL ameliorated oxidative stress by significantly increasing superoxide dismutase and glutathione peroxidase levels and decreasing malondialdehyde level in WPMY-1 cells and rats (P<0.01 or P<0.05). SSTL significantly elevated the expressions of Nrf2, HO-1, NAD(P)H quinone oxidoreductase 1 (NQO-1), and Smad7 proteins in both cells and rats, and significantly decreased the expressions of TGF-β1, collagen I, α-smooth muscle actin and Smad4 proteins (P<0.01 or P<0.05). SSTL also elevated the content of Nrf2 mRNA and decreased the content of TGF-β1 mRNA in cells and rats (P<0.01 or P<0.05). The Nrf2 inhibitor ML385 was added in in vitro experiments to further validate the pathway relevance. CONCLUSION SSTL was effective in improving PF in vivo and in vitro, and its mechanism of action may function through the Nrf2/TGF-β1 signaling pathway.
Male ; NF-E2-Related Factor 2/metabolism* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Humans ; Fibrosis ; Prostate/drug effects* ; Cell Proliferation/drug effects* ; Capsules ; Cell Movement/drug effects* ; Oxidative Stress/drug effects* ; Rats

Ovulatory dysfunction (OD) is one of the main causes of infertility in women of childbearing age, which not only affects their reproductive ability, but also physical and mental health. Traditional treatment strategies have limited efficacies, and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology. This review explores the pathophysiological characteristics and related induction mechanisms of OD, and evaluates the current cutting-edge advances in its treatments. It emphasizes the potentials of biomedicines strategies such as hydrogels, nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy. By mimicking natural physiological processes, and achieving controlled drug release, these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming, tissue repair, and metabolic and immune regulation. Despite the promising progress, there are still challenges in terms of biomedical complexity, differences between animal models and human physiology, and the demand for intelligent drug carriers in the therapy of OD. Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration, promoting the development of reproductive regenerative medicine.

Objective:To investigate the value of transanal multipoint full-layer puncture biopsy (TMFP) in predicting pathological complete response (pCR) after neoadjuvant radiotherapy and chemotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to establish a predictive model for providing clinical guidance regarding the treatment of LARC.Methods:In this multicenter, prospective, cohort study, we collected data on 110 LARC patients from four hospitals between April 2020 and March 2023: Beijing Chaoyang Hospital of Capital Medical University (50 patients), Beijing Friendship Hospital of Capital Medical University (41 patients), Qilu Hospital of Shandong University (16 patients), and Zhongnan Hospital of Wuhan University (three patients). The patients had all received TMFP after completing standard nCRT. The variables studied included (1) clinicopathological characteristics; (2) clinical complete remission (cCR) and efficacy of TMFP in determining pCR after NCRT in LARC patients; and (3) hospital attended, sex, age, clinical T- and N-stages, distance between the lower margin of the tumor and the anal verge, baseline and post-radiotherapy serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 concentrations, chemotherapy regimen, use of immunosuppressants with or without radiotherapy, radiation therapy dosage, interval between surgery and radiotherapy, surgical procedure, clinical T/N stage after radiotherapy, cCR, pathological results of TMFP, puncture method (endoscopic or percutaneous), and number and timing of punctures. Single-factor and multifactorial logistic regression analysis were used to determine the factors affecting pCR after NCRT in LARC patients. A prediction model was constructed based on the results of multivariat analysis and the performance of this model evaluated by analyzing subject work characteristics (ROC), calibration, and clinical decision-making (DCA) curves. pCR was defined as complete absence of tumor cells on microscopic examination of the surgical specimens of rectal cancer (including lymph node dissection) after NCRT, that is, ypT0+N0. cCR was defined according to the Chinese Neoadjuvant Rectal Cancer Waiting Watch Database Study Collaborative Group criteria after treatment, which specify an absence of ulceration and nodules on endoscopy; negative rectal palpation; no tumor signals on rectal MRI T2 and DWI sequences; normal serum CEA concentrations, and no evidence of recurrence on pelvic computed tomography/magnetic resonance imaging.Results:Of the 110 patients, 45 (40.9%) achieved pCR after nCRT, which was combined with immune checkpoint inhibitors in 34 (30.9%). cCR was diagnosed before puncture in 38 (34.5%) patients, 43 (39.1%) of the punctures being endoscopic. There were no complications of puncture such as enterocutaneous fistulae, vaginal injury, prostatic injury, or presacral bleeding . Only one (2.3%) patient had a small amount of blood in the stools, which was relieved by anal pressure. cCR had a sensitivity of 57.8% (26/45) for determining pCR, specificity of 81.5% (53/65), accuracy of 71.8% (79/110), positive predictive value 68.4% (26/38), and negative predictive value of 73.6% (53/72). In contrast, the sensitivity of TMFP pathology in determining pCR was 100% (45/45), specificity 66.2% (43/65), accuracy 80.0% (88/110), positive predictive value 67.2% (45/67), and negative predictive value 100.0% (43/43). In this study, the sensitivity of TMFP for pCR (100.0% vs. 57.8%, χ 2=24.09, P<0.001) was significantly higher than that for cCR. However, the accuracy of pCR did not differ significantly (80.0% vs. 71.8%, χ 2=2.01, P=0.156). Univariate and multivariate logistic regression analyses showed that a ≥4 cm distance between the lower edge of the tumor and the anal verge (OR=7.84, 95%CI: 1.48-41.45, P=0.015), non-cCR (OR=4.81, 95%CI: 1.39-16.69, P=0.013), and pathological diagnosis by TMFP (OR=114.29, the 95%CI: 11.07-1180.28, P<0.001) were risk factors for pCR after NCRT in LARC patients. Additionally, endoscopic puncture (OR=0.02, 95%CI: 0.05-0.77, P=0.020) was a protective factor for pCR after NCRT in LARC patients. The area under the ROC curve of the established prediction model was 0.934 (95%CI: 0.892-0.977), suggesting that the model has good discrimination. The calibration curve was relatively close to the ideal 45° reference line, indicating that the predicted values of the model were in good agreement with the actual values. A decision-making curve showed that the model had a good net clinical benefit. Conclusion:Our predictive model, which incorporates TMFP, has considerable accuracy in predicting pCR after nCRT in patients with locally advanced rectal cancer. This may provide a basis for more precisely selecting individualized therapy.

Objective To evaluate the predictors of biochemical recurrence after laparoscopic radical prostatectomy.Methods The study cohort consisted of 416 consecutive prostatecancer patients who underwent radical prostatectomy in Zhongshan Hospital,Fudan University between Jan 2016 and Jun 2018.No patient received adjuvant therapy until documented biochemical recurrence.Biochemical recurrence-free survival(BCRFS)was estimated using the Kaplan-Meier method.Univariable and multivariable Cox proportional hazards regression models were utilized to determine variables predictive of biochemical recurrence.Results The median follow-up period was 174 weeks(inter quartile range 133-209 weeks).The overall biochemical recurrence rate was 21.39%(88/416).The time to biochemical recurrence was(51.11±47.71)weeks.Until the end of follow-up,the biochemical recurrence rates were 10%(1/10),6.12%(3/49),16.41%(43/262)and 43.16%(41/95)for low-risk,medium-risk,high-risk and locally advanced prostate cancer,respectively.On multivariable analysis,tumor invasion of the seminal vesicles(HR:2.119,95%CI:1.154-3.891,P=0.016);Seminal vesicle invasion(HR:1.824,95%CI:1.034-3.220,P=0.038),Gleason score≥8(HR:2.746,95%CI:1.268-5.943,P=0.010),prostate-specific antigen(PSA)=10-20 ng/mL(HR:4.240,95%CI:2.550-7.050,P<0.001);PSA>20 ng/mL(HR:6.341,95%CI:3.296-12.202,P<0.001)were the main predictors of biochemical recurrence.Conclusion Laparoscopic radical prostatectomy provides effective control of biochemical recurrence during the mid-term follow-up period.Tumor invasion of the seminal vesicles,seminal vesicle invasion,GS≥8,PSA=10-20 ng/mL,PSA>20 ng/mL were important predictors of biochemical recurrence after radical prostatectomy.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]