Objective To investigate the effects and related mechanisms of mitochondrial-derived peptide MOTS-c on glycochenodeoxycholic acid (GCDCA)-induced injury in human hepatocytes (THLE-3 cells). Methods THLE-3 cells were cultured in vitro and treated with different concentrations of GCDCA and MOTS-c. The optimal concentrations of GCDCA and MOTS-c were determined by cell counting kit (CCK)-8 method. Subsequently, THLE-3 cells were treated or pre-treated with GCDCA (200 µmol/L), MOTS-c (15, 30, 60 µmol/L), the multidrug resistance protein 2 (MRP2) inhibitor Probenecid (500 µmol/L), and the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 (10 µmol/L). Cell proliferation was assessed by CCK-8 method. Lactate dehydrogenase (LDH) levels in the culture medium were measured by biochemical method. Cell apoptosis rates were determined by flow cytometry. MRP2 messenger RNA (mRNA) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). MRP2 and Nrf2 protein expression levels were analyzed by Western blotting. Results As the concentration of GCDCA increased, the proliferation activity of THLE-3 cells gradually decreased, while LDH activity in the culture medium and apoptosis levels increased, and the expression levels of MRP2 in the cells decreased (all P<0.05). Treatment with 30 and 60 µmol/L MOTS-c significantly enhanced the proliferation activity of THLE-3 cells exposed to GCDCA, upregulated the expression of MRP2 and Nrf2, and reduced LDH activity and apoptosis levels (all P<0.05). Co-treatment with Probenecid partially reversed the protective effects of MOTS-c on GCDCA-induced THLE-3 cells injury, while co-treatment with ML385 partially inhibited the induction of MRP2 expression by MOTS-c in THLE-3 cells exposed to GCDCA. Conclusions MOTS-c may alleviate GCDCA-induced injury in human hepatocytes (THLE-3 cells), and its mechanism may be related to the upregulation of MRP2 expression mediated by Nrf2.

Objective To explore the feasibility of applying artificial intelligence (AI) technology in chromosomal aberration (CA) analysis for occupational health surveillance of radiation workers and in biological dose estimation during nuclear emergency responses. Methods Peripheral blood samples from healthy volunteers were irradiated in vitro with X-rays and cobalt-60 (⁶⁰Co) γ rays. Chromosome slides were prepared using an automated harvesting and dropping device. The data training and outcome evaluation of CA analysis was performed on the AI software using chromosome images from occupational medical examination of radiation workers from the current lab or chromosome slides from blood samples irradiated with X-rays. The trained AI software was then used to assist in CA analysis and biological dose estimation among occupational medical examination of radiation workers, with results compared with manual reading and actual exposure doses. Results The trained AI software achieved a CA recognition accuracy of 95.11%. In the occupational health examination of radiation workers, the positive CA detection rate using AI + manual review was 2.25% higher than that in manual reviewing alone. The errors in biological dose estimation for ⁶⁰Co γ rays and X-rays using AI + manual review analysis were 11.86% and 7.33%, respectively, both within the acceptable 20.00% error margin. Conclusion AI + manual review can be effectively applied in CA analysis for occupational health examination and biological dose estimation during nuclear emergencies, significantly improving analysis efficiency.

OBJECTIVE: To construct machine learning prediction model for sepsis-associated encephalopathy (SAE), and analyze the application value of the model on early identification of SAE risk in elderly septic patients. METHODS: Patients aged over 60 years with a primary diagnosis of sepsis admitted to intensive care unit (ICU) from 2008 to 2023 were selected from Medical Information Mart for Intensive Care-IV 2.2 (MIMIC-IV 2.2). Demographic variables, disease severity scores, comorbidities, interventions, laboratory indicators, and hospitalization details were collected. Key factors associated with SAE were identified using univariate Logistic regression analysis. The data were randomly divided into training and validation sets in a 7 : 3 ratio. Multivariable Logistic regression analysis was conducted in the training set and visualized using a nomogram model for prediction of SAE. The discrimination of the model was evaluated in the validation set using the receiver operator characteristic curve (ROC curve), and its calibration was assessed using calibration curve. Furthermore, multiple machine learning algorithms, including multi-layer perceptron (MLP), support vector machine (SVM), naive bayes (NB), gradient boosting machine (GBM), random forest (RF), and extreme gradient boosting (XGB), were constructed in the training set. Their predictive performance was subsequently evaluated on the validation set. Taking the XGB model as an example, the interpretability of the model through the SHapley Additive exPlanations (SHAP) algorithm was enhanced to identify the key predictive factors and their contributions. RESULTS: A total of 2 204 septic patients were finally enrolled, of whom 840 developed SAE (38.1%). A total of 21 variables associated with SAE were screened through univariate Logistic regression analysis. Multivariable Logistic regression analysis showed that endotracheal intubation [odds ratio (OR) = 0.40, 95% confidence interval (95%CI) was 0.19-0.88, P < 0.001], oxygen therapy (OR = 0.76, 95%CI was 0.53-0.95, P = 0.023), tracheotomy (OR = 0.20, 95%CI was 0.07-0.53, P < 0.001), continuous renal replacement therapy (CRRT; OR = 0.32, 95%CI was 0.15-0.70, P < 0.001), cerebrovascular disease (OR = 0.31, 95%CI was 0.16-0.60, P < 0.001), rheumatic disease (OR = 0.44, 95%CI was 0.19-0.99, P < 0.001), male (OR = 0.68, 95%CI was 0.54-0.86, P = 0.001), and maximum anion gap (AG; OR = 0.95, 95%CI was 0.93-0.97, P < 0.001) were associated with an decreased probability of SAE, and age (OR = 1.05, 95%CI was 1.03-1.06, P < 0.001), acute physiology score III (APSIII; OR = 1.02, 95%CI was 1.01-1.02, P < 0.001), Oxford acute severity of illness score (OASIS; OR = 1.04, 95%CI was 1.03-1.06, P < 0.001), and length of hospital stay (OR = 1.01, 95%CI was 1.01-1.02, P < 0.001) were associated with an increased probability of SAE. A nomogram model was constructed based on these variables. In the validation set, ROC curve analysis showed that the model achieved an area under the ROC curve (AUC) of 0.723, and the calibration curve showed good consistency between the predicted probability of the model and the observed probability. Among the machine learning algorithms, including MLP, SVM, NB, GBM, RF, and XGB, the SVM model and RF model demonstrated relatively good predictive performance, with AUC of 0.748 and 0.739, respectively, and the sensitivity was both exceeding 85%. The predictive performance of the XGB model was explained through SHAP analysis, and the results indicated that APSIII score (SHAP value was 0.871), age (SHAP value was 0.521), and OASIS score (SHAP value was 0.443) were important factors affecting the predictive performance of the model. CONCLUSIONS The machine learning-based SAE prediction model exhibits good predictive capability and holds significant application value for the early identification of SAE risk in elderly septic patients.
Humans ; Machine Learning ; Aged ; Sepsis-Associated Encephalopathy ; Sepsis/complications* ; Intensive Care Units ; Logistic Models ; Middle Aged ; Male ; ROC Curve ; Female ; Bayes Theorem ; Nomograms ; Support Vector Machine ; Algorithms

Objective To estimate the biological dose in a patient who developed radiation dermatitis after a local X-ray exposure incident. Methods Peripheral blood samples, which were used to performed lymphocyte chromosome aberration analysis, were collected from the patient at 54 and 102 days after the last exposure. Biological dose in the patient was estimated using four published X-ray dose-effect calibration curves for chromosomal aberrations. The absorbed dose in the patient was reconstructed using Dolphin′s model and time correction factors. Results The abnormal rates of chromosome aberration at 54 and 102 days after exposure were 1.00% and 0.40%, respectively. Based on the four calibration curves, the estimated local exposure dose at 54 day ranged from 3.59 to 10.51 Gy, and the time-corrected whole-body equivalent dose ranged from 0.27 to 0.87 Gy. The local dose estimated at 102 days ranged from 2.24 to 6.64 Gy, with a time-corrected whole-body equivalent dose of 0.12 to 0.60 Gy, which differed from the day-54 estimates. The biological doses estimated by both methods were lower than the physical dose (29.43 Gy). Conclusion The estimation of local biological dose of patient various in four dose-effect curves selected in this study. Delayed blood sampling will lead to underestimate biological dose. Early blood collection after radiation incidents is critical to ensure accuracy and reliability. Moreover, biological dose reconstruction methods for complex exposure scenarios require further research to improve the accracy of emergency response in radiation accidents.

Objective:To develop and evaluate a nomogram prediction model for the 3-month mortality risk of patients with sepsis-associated acute kidney injury (S-AKI).Methods:Based on the American Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ), clinical data of S-AKI patients from 2008 to 2021 were collected.Initially, 58 relevant predictive factors were included, with all-cause mortality within 3 months as the outcome event. The data were divided into training and testing sets at a 7∶3 ratio. In the training set, univariate Logistic regression analysis was used for preliminary variable screening. Multicollinearity analysis, Lasso regression, and random forest algorithm were employed for variable selection, combined with the clinical application value of variables, to establish a multivariable Logistic regression model, visualized using a nomogram. In the testing set, the predictive value of the model was evaluated through internal validation. The receiver operator characteristic curve (ROC curve) was drawn, and the area under the curve (AUC) was calculated to evaluate the discrimination of nomogram model and Oxford acute severity of illness score (OASIS), sequential organ failure assessment (SOFA), and systemic inflammatory response syndrome score (SIRS). The calibration curve was used to evaluate the calibration, and decision curve analysis (DCA) was performed to assess the net benefit at different probability thresholds.Results:Based on the survival status at 3 months after diagnosis, patients were divided into 7?768 (68.54%) survivors and 3?566 (31.46%) death. In the training set, after multiple screenings, 7 variables were finally included in the nomogram model: Logistic organ dysfunction system (LODS), Charlson comorbidity index, urine output, international normalized ratio (INR), respiratory support mode, blood urea nitrogen, and age. Internal validation in the testing set showed that the AUC of nomogram model was 0.81 [95% confidence interval (95% CI) was 0.80-0.82], higher than the OASIS score's 0.70 (95% CI was 0.69-0.71) and significantly higher than the SOFA score's 0.57 (95% CI was 0.56-0.58) and SIRS score's 0.56 (95% CI was 0.55-0.57), indicating good discrimination. The calibration curve demonstrated that the nomogram model's calibration was better than the OASIS, SOFA, and SIRS scores. The DCA curve suggested that the nomogram model's clinical net benefit was better than the OASIS, SOFA, and SIRS scores at different probability thresholds. Conclusions:A nomogram prediction model for the 3-month mortality risk of S-AKI patients, based on clinical big data from MIMIC-Ⅳ and including seven variables, demonstrates good discriminative ability and calibration, providing an effective new tool for assessing the prognosis of S-AKI patients.

Objective To observe the optimal target areas for shear wave velocity(SWV)evaluation on stages of chronic kidney disease(CKD)in different sides(left,right),different parts(upper pole,middle part and lower pole)and different tissue(renal cortex,renal medulla,renal sinus)of kidney.Methods Sixty-five CKD patients(130 kidneys)were retrospectively collected.SWV were compared between different sides,among different parts and tissue of kidney.The optimal regions for evaluating CKD stages were screened.Results No significant difference of SWV was found between left and right kidneys in same parts for same tissue(all P＞0.05),while significant differences of SWV of the same tissue were noticed among upper pole,middle part and lower part of kidney on the same side(all P＜0.05),i.e at upper pole＞at middle part＞at lower pole.Significant differences of SWV were also observed among renal cortex,medulla and sinus of kidney in the same side and parts(all P＜0.05),and the sinus had the highest SWV.Intraclass correlation coefficient analysis showed that the repeatability of the measurements of SWV was the best at the middle part of kidney.Besides,significant differences of SWV were found between renal cortex and medulla at the middle part of kidney among patients with stages 1,2,3 and 4-5 CKD(all P＜0.05),while the highest SWV were observed in patients with 4-5 stage CKD(all P＜0.05).SWV of renal cortex and medulla at middle part were positively correlated with CKD stages(both P＜0.01),the area under the curve of them for evaluating stage of CKD was 0.802 and 0.774,respectively.Conclusion The optimal target areas for SWV evaluation on stages of CKD were renal cortex and medulla at middle part of kidney.

Objective:To investigate the pattern of distribution of the circumferential fascia of the rectum and elucidate its clinical implications.Methods:In this descriptive study, we examined the gross anatomy of four male hemipelvic cadaveric specimens from the Department of Anatomy at Fujian Medical University and the histological features of 16 fresh postoperative specimens from patients who had undergone total mesorectal excision for rectal cancer at the Department of Colorectal Surgery, Union Hospital, Fujian Medical University, between January and December 2022. The resultant combination of gross anatomical and histological features was employed to assess the following areas: (1)the morphology of the anterior mesorectum and fascia at the peritoneal reflection; (2)the caudal attachment point of Denonvilliers' fascia; (3) the fusion area of the pelvic plexus and the pre-hypogastric fascia; (4)the lateral and posterior attachment edges of the rectosacral fascia; and (5) selected histological features.Results:Our findings were as follows. (1) At the peritoneal reflection, the anterior mesorectum forms a triangular fat pad with a dense fascial structure. The base of this pad extends anteriorly across the most caudal point of the peritoneal reflection, with Denonvilliers' fascia originating from the anterior side of the triangle, near the bladder side of the peritoneum craniad to the peritoneal reflection. (2) The caudal attachment of Denonvilliers' fascia is at the angle between the seminal vesicles, the ampulla of the vas deferens, and the prostate. It adheres tightly to the prostatic capsule and vascular bundles pass through its cephalic side. (3) The pre-hypogastric fascia transitions laterally to merge with Denonvilliers' fascia; its middle part being inseparable from the main body of the pelvic plexus, which gives rise to the nerves that innervate the rectum. (4) The rectosacral fascia is formed by fusion of the fascia propria with the pre-hypogastric fascia. The resultant fused fascia bifurcates into two leaves on the right side; the outer leaf being the pre-hypogastric fascia and the inner leaf the fascia propria. (5) Histologically, the peritoneal reflection zone shows cuboidal epithelium of the peritoneum at its lowest point with no detectable origin of Denonvilliers' fascia. The anterior side of the peritoneal reflection, from which Denonvilliers' fascia originates, has a dense double-layered fascial structure comprising thick collagen fiber (16/16). The fascia propria exhibits a thinner and looser collagen fiber structure and its origin varies between individuals, 13/16 originating together with Denonvilliers' fascia from the craniad side of the peritoneal reflection, and 3/16 originating separately from the most caudal point of the peritoneal reflection. The caudal edge of Denonvilliers' fascia has a double-layered fascial structure with multiple S100-stained areas. The posterior edge of the rectosacral fascia has a fused fascial structure, thick nerve fibers being clearly observable between collagen fibers originating from the pre-hypogastric fascia under high magnification. The lateral edge of the rectosacral fascia extends interiorly, maintains the integrity of the fascia propria.Conclusions:In this study, we investigated the pattern of distribution of the circumferential fascia of the rectum by cadaveric dissection and histological examination of postoperative specimens. We found that the anterior mesorectum forms a triangular fat pad that can serve as a reference for dissection anterior to Denonvilliers' fascia, by making incisions 1 cm above the peritoneal reflection. The region of fusion of Denonvilliers' fascia with the prostatic capsule on the caudal side is rich in neurovascular bundles, contradicting the traditional view of a retroprostatic plane. This finding supports the practice of cutting Denonvilliers' fascia 0.5 cm above the base of the seminal vesicles. The fusion of the fascia propria with the pre-hypogastric fascia posteriorly forms the rectosacral fascia, which bifurcates into two leaves on both sides of the rectum, the inner leaf being the fascia propria and the outer leaf the pre-hypogastric fascia. These transition anteriorly to become Denonvilliers' fascia and fuse densely with the main body of the pelvic plexus on both sides. These findings provide a theoretical foundation for protecting the pelvic plexus and hypogastric nerve by transecting Denonvilliers' fascia and then dissecting in a top-to-bottom direction (i.e., from anterior to caudal), ultimately leading to the transection of the pre-hypogastric fascia.

Objective:To explore the efficacy and safety of hyaluronic acid filler VYC-20L for full-face lifting in aesthetic seeking patients.Methods:Between November 2020 and November 2021, a total of 216 aesthetic seeking patients were enrolled in Shanghai Chingho Outpatient Department, World Path Clinic International, Qihe Medical Beauty Hospital and Qinhuangdao Qiaozhi Beauty Hospital, including 37 males and 179 females, aged 25-67 (41.42±10.93) years. According to the needs and requirements, the novel injection technique of " ROYGBbP-rainbow lifting method" was used to inject hyaluronic acid filler VYC-20L. The global aesthetic improvement scale (GAIS) and the treatment satisfaction questionnaires were scored and evaluated before the injection, and at follow-up visits 1, 6, and 12 months after the injection. Any adverse reaction or adverse events presenting or reported by the patients post-injection were recorded.Results:At 1 month, 6 months and 12 months after the injection, about 203 (94.0%), 208 (96.3%) and 205 (94.9%) of the aesthetic seeking patients rated their full-face appearance as " excellently improved" or " much improved" on the GAIS, respectively. And 12 months after the injection, the overall facial satisfaction scores and appearance recognition scores of all aesthetic seeking patients were all significantly higher than those before injection ( P<0.01). 197 (91.2%), 198 (91.7%) and 198 (91.7%) of the aesthetic seeking patients were " very satisfied" or " relatively satisfied" with the treatment at 1 month, 6 months and 12 months, respectively. Treatment site responses most frequently reported were tenderness, bruising, topical swelling and skin redness. Most of the symptoms were moderate or mild feeling, lasting for no more than two weeks. Conclusions:The application of hyaluronic acid filler VYC-20L is safe and effective for full-face lifting in aesthetic seeking patients, which can significantly improve facial sagging and rejuvenate the face. The effect of improvements can last for 12 months.

Objective Scutellaria baicalensis stems and leaves glucuronic hydrolase(sbsl GUS)was used to enzymatically hydrolyze scutellarin in Erigeron breviscapus(Vant.)Hand.Mazz.to prepare scutellarein,and the high-purity scutellarein was obtained through separation and purification.Methods Orthogonal experiments were used to optimize the process parameters for the extraction of Erigeron breviscapus(Vant.)Hand.Mazz..Using the rate of enzymatic hydrolysis conversion of scutellarin as the index,the amount of enzyme,pH,temperature,time and antioxidant were investigated,and the preparation process parameters of scutellarein were optimized.Ethanol extraction,activated carbon decolorization,and fractional crystallization were used to purify the crude extract.Results The extraction process was determined to be:segments of Erigeron breviscapus were decocted twice with 10 times water for 1 hour each time.The preparation process of scutellarein was as follows:the amount of sbsl GUS extract and Erigeron breviscapus decoction was 1∶10 based on crude drugs,0.5%sodium metabisulfite was added,pH value was about 6.0,the temperature was about 45℃,and the time was 20 hours.The crude extract of scutellarein with the content more than 60%was obtained.The crude extract was purified by fractional crystallization,refluxed with 80%ethanol,decolorized with activated carbon,concentrated and crystallized,and the scutellarein extract with content more than 85%was obtained.Conclusion sbsl GUS enzymatic hydrolysis technology,which was used to prepare scutellarein,is simple and feasible.This study provides a new way for the manufacture of scutellarein.

Objective:To investigate the pattern of distribution of the circumferential fascia of the rectum and elucidate its clinical implications.Methods:In this descriptive study, we examined the gross anatomy of four male hemipelvic cadaveric specimens from the Department of Anatomy at Fujian Medical University and the histological features of 16 fresh postoperative specimens from patients who had undergone total mesorectal excision for rectal cancer at the Department of Colorectal Surgery, Union Hospital, Fujian Medical University, between January and December 2022. The resultant combination of gross anatomical and histological features was employed to assess the following areas: (1)the morphology of the anterior mesorectum and fascia at the peritoneal reflection; (2)the caudal attachment point of Denonvilliers' fascia; (3) the fusion area of the pelvic plexus and the pre-hypogastric fascia; (4)the lateral and posterior attachment edges of the rectosacral fascia; and (5) selected histological features.Results:Our findings were as follows. (1) At the peritoneal reflection, the anterior mesorectum forms a triangular fat pad with a dense fascial structure. The base of this pad extends anteriorly across the most caudal point of the peritoneal reflection, with Denonvilliers' fascia originating from the anterior side of the triangle, near the bladder side of the peritoneum craniad to the peritoneal reflection. (2) The caudal attachment of Denonvilliers' fascia is at the angle between the seminal vesicles, the ampulla of the vas deferens, and the prostate. It adheres tightly to the prostatic capsule and vascular bundles pass through its cephalic side. (3) The pre-hypogastric fascia transitions laterally to merge with Denonvilliers' fascia; its middle part being inseparable from the main body of the pelvic plexus, which gives rise to the nerves that innervate the rectum. (4) The rectosacral fascia is formed by fusion of the fascia propria with the pre-hypogastric fascia. The resultant fused fascia bifurcates into two leaves on the right side; the outer leaf being the pre-hypogastric fascia and the inner leaf the fascia propria. (5) Histologically, the peritoneal reflection zone shows cuboidal epithelium of the peritoneum at its lowest point with no detectable origin of Denonvilliers' fascia. The anterior side of the peritoneal reflection, from which Denonvilliers' fascia originates, has a dense double-layered fascial structure comprising thick collagen fiber (16/16). The fascia propria exhibits a thinner and looser collagen fiber structure and its origin varies between individuals, 13/16 originating together with Denonvilliers' fascia from the craniad side of the peritoneal reflection, and 3/16 originating separately from the most caudal point of the peritoneal reflection. The caudal edge of Denonvilliers' fascia has a double-layered fascial structure with multiple S100-stained areas. The posterior edge of the rectosacral fascia has a fused fascial structure, thick nerve fibers being clearly observable between collagen fibers originating from the pre-hypogastric fascia under high magnification. The lateral edge of the rectosacral fascia extends interiorly, maintains the integrity of the fascia propria.Conclusions:In this study, we investigated the pattern of distribution of the circumferential fascia of the rectum by cadaveric dissection and histological examination of postoperative specimens. We found that the anterior mesorectum forms a triangular fat pad that can serve as a reference for dissection anterior to Denonvilliers' fascia, by making incisions 1 cm above the peritoneal reflection. The region of fusion of Denonvilliers' fascia with the prostatic capsule on the caudal side is rich in neurovascular bundles, contradicting the traditional view of a retroprostatic plane. This finding supports the practice of cutting Denonvilliers' fascia 0.5 cm above the base of the seminal vesicles. The fusion of the fascia propria with the pre-hypogastric fascia posteriorly forms the rectosacral fascia, which bifurcates into two leaves on both sides of the rectum, the inner leaf being the fascia propria and the outer leaf the pre-hypogastric fascia. These transition anteriorly to become Denonvilliers' fascia and fuse densely with the main body of the pelvic plexus on both sides. These findings provide a theoretical foundation for protecting the pelvic plexus and hypogastric nerve by transecting Denonvilliers' fascia and then dissecting in a top-to-bottom direction (i.e., from anterior to caudal), ultimately leading to the transection of the pre-hypogastric fascia.