Objective:To analyze the prognostic factors of patients with liver cirrhosis and portal vein thrombosis (PVT), and to construct a prognostic prediction model based on machine learning methods.Methods:The clinical data of 388 patients with liver cirrhosis and PVT admitted to the Fifth Medical Center of PLA General Hospital from January 2022 to April 2024 were retrospectively collected and analyzed, including 243 males and 145 females, aged (56.9±10.9) years. A total of 388 patients were randomly divided into the training set ( n=310) and the testing set ( n=78) in a 4∶1 ratio. The Boruta algorithm was used to screen the key features in the training set, and then four machine learning algorithms, including random forest, support vector machine, generalized linear model and Bayesian, were used to establish a survival prediction model. Model performance was evaluated by the receiver operating characteristic (ROC) curves of the test set and the training set. The patients were followed up for 1 year for survival. Sort the importance of features based on the SHAP value. Results:There were 250 patients (80.6%) who survived and 60 (19.4%) who died. The model for end-stage liver disease score, total bilirubin, serum creatinine, prothrombin time, international normalized ratio, D-dimer, white blood cell count, severe ascites ratio, and Child-Pugh grade C ratio of liver function in the death group were higher than those in the survival group, and the red blood cell count and hematocrit were lower than those in the survival group, and the differences were statistically significant (all P<0.05). The areas under the ROC curve for predicting survival by random forest, support vector machine, generalized linear model and Bayesian model were 0.92, 0.78, 0.81 and 0.71 in the training set, and the area under the ROC curve in the testing set were 0.81, 0.72, 0.67 and 0.68, respectively. Random forest had the best prediction performance, with an accuracy of 81.7%, a sensitivity of 84.6%, and a specificity of 76.9% in the testing set. In the analysis of the importance of characteristic parameters of the random forest model, total bilirubin, red blood cells, hematocrit, serum creatinine, ascites classification, etc. had a relatively high contribution to the model. Conclusion:In the survival prediction model of patients with liver cirrhosis and PVT based on machine learning algorithm, the random forest model had high prediction performance, and total bilirubin may be the most important factor affecting the survival prognosis of patients.

Objective:To analyze the prognostic factors of patients with liver cirrhosis and portal vein thrombosis (PVT), and to construct a prognostic prediction model based on machine learning methods.Methods:The clinical data of 388 patients with liver cirrhosis and PVT admitted to the Fifth Medical Center of PLA General Hospital from January 2022 to April 2024 were retrospectively collected and analyzed, including 243 males and 145 females, aged (56.9±10.9) years. A total of 388 patients were randomly divided into the training set ( n=310) and the testing set ( n=78) in a 4∶1 ratio. The Boruta algorithm was used to screen the key features in the training set, and then four machine learning algorithms, including random forest, support vector machine, generalized linear model and Bayesian, were used to establish a survival prediction model. Model performance was evaluated by the receiver operating characteristic (ROC) curves of the test set and the training set. The patients were followed up for 1 year for survival. Sort the importance of features based on the SHAP value. Results:There were 250 patients (80.6%) who survived and 60 (19.4%) who died. The model for end-stage liver disease score, total bilirubin, serum creatinine, prothrombin time, international normalized ratio, D-dimer, white blood cell count, severe ascites ratio, and Child-Pugh grade C ratio of liver function in the death group were higher than those in the survival group, and the red blood cell count and hematocrit were lower than those in the survival group, and the differences were statistically significant (all P<0.05). The areas under the ROC curve for predicting survival by random forest, support vector machine, generalized linear model and Bayesian model were 0.92, 0.78, 0.81 and 0.71 in the training set, and the area under the ROC curve in the testing set were 0.81, 0.72, 0.67 and 0.68, respectively. Random forest had the best prediction performance, with an accuracy of 81.7%, a sensitivity of 84.6%, and a specificity of 76.9% in the testing set. In the analysis of the importance of characteristic parameters of the random forest model, total bilirubin, red blood cells, hematocrit, serum creatinine, ascites classification, etc. had a relatively high contribution to the model. Conclusion:In the survival prediction model of patients with liver cirrhosis and PVT based on machine learning algorithm, the random forest model had high prediction performance, and total bilirubin may be the most important factor affecting the survival prognosis of patients.

Objective:To investigate the disease control rate and its influencing factors in patients with progressive non-segmental vitiligo after combined treatment with systemic compound betamethasone injection (CBI) .Methods:A retrospective analysis was conducted on the patients with progressive non-segmental vitiligo, who visited and were treated with CBI in the Department of Dermatology, Hangzhou Third People′s Hospital from October 2022 to April 2023. The disease control rate was analyzed after 3-month treatment. Effects of clinical factors such as disease onset characteristics, duration, disease condition and treatment methods on the disease control rate were analyzed. Chi-square test was used for comparisons of enumeration data between groups, and logistic regression analysis was conducted to analyze factors influencing the efficacy.Results:A total of 145 progressive non-segmental vitiligo patients treated with CBI were collected, including 56 males and 89 females, aged 14 - 67 (35.43 ± 11.54) years. Among the 18 patients having received an intramuscular injection of CBI, 10 (55.6%) obtained stable condition; among the 105 having received 2 injections of CBI, 60 (59.0%) obtained stable condition; among the 22 having received 3 or 4 injections of CBI, 12 (54.5%) obtained stable condition. The overall disease control rate after treatment was 57.9% (84 cases). The disease control rate was significantly higher in the patients with the lesional area < 1% body surface area (BSA) (42/47, 89.4%) than in those with the lesional area ≥ 1% BSA (42/98, 42.9%; P < 0.001), significantly higher in the patients with disease duration ≤ 2 years (32/41, 78.0%) than in those with disease duration > 2 years (52/104, 50.0%; P < 0.05), and significantly higher in the patients treated with CBI combined with phototherapy (33/44, 75.0%) than in those treated with CBI alone (21/44, 47.7%; χ2 = 6.90, P = 0.009), but significantly lower in the patients with special clinical markers (Koebner phenomenon, trichrome vitiligo, confetti-like depigmentation, inflammatory vitiligo, etc., 4/21, 19.9%) than in those without special clinical markers (80/124, 64.5%, P < 0.001). Among the patients with the lesional area ≥ 1% BSA and receiving 2 injections of CBI, the disease control rate was also significantly higher in the patients treated with CBI combined with phototherapy (21/36, 58.3%) than in those treated with CBI alone (12/37, 32.4%; χ2 = 4.94, P = 0.026). There was no significant difference in the disease control rate after the treatment between the patients with first-onset and reccurrent vitiligo, between those with and without predisposing factors, between those with and without family history, among those with different vitiligo disease activity scores, among those with different number of injections, as well as among those with different treatment intervals (all P > 0.05). Multivariate logistic regression analysis showed that the lesional area ( OR = 8.11, 95% CI: 2.74 - 24.04), disease duration ( OR = 0.26, 95% CI: 0.07 - 0.99), having or not having special clinical markers ( OR = 6.37, 95% CI: 1.72 - 23.57), and whether or not receiving combined phototherapy ( OR = 0.34, 95% CI: 0.15 - 0.77) were factors influencing the efficacy (all P < 0.05) . Conclusion:CBI may be suitable for the treatment of mild to moderate progressive vitiligo, especially for patients with lesional area < 1% BSA, while not for those with lesional area > 5% BSA, and combining phototherapy may improve the control rate of progressive vitiligo.

Objective:To assess the value of culture of epidermal melanocytes from negative-pressure suction blisters in the auxiliary diagnosis of segmental vitiligo-like nevus depigmentosus.Methods:Between June 2019 and March 2020, 8 patients with segmental vitiligo-like nevus depigmentosus, who met the Coupe′s clinical diagnostic criteria, were enrolled from Department of Dermatology, Hangzhou Third People′s Hospital. All patients were evaluated by the Wood′s lamp, reflectance confocal microscopy (RCM) , 308-nm excimer laser radiation, and in vitro culture of epidermal melanocytes from negative-pressure suction blisters. Results:Among the 8 patients, fluorescence was observed in 6 under the Wood′s lamp, dermal papillary rings were incomplete or absent in 4 as shown by RCM, and 5 experienced no repigmentation after 308-nm excimer laser radiation. Among the 8 patients, in vitro cultured lesional melanocytes were all positive for ferrous sulfate staining, yellowish-white precipitates were obtained after digestion and centrifugation of the melanocytes, and stage Ⅰ-Ⅲ melanosomes were observed in the cytoplasm of melanocytes under the electron microscope; however, the precipitates were black in color after digestion and centrifugation of the melanocytes collected from the normal skin tissues at the contralateral anatomical site, and stageⅠ-Ⅳ melanosomes were seen in the cytoplasm of the melanocytes under the electron microscope. Conclusion:Culture of epidermal melanocytes from negative-pressure suction blisters may facilitate the diagnosis of segmental vitiligo-like nevus depigmentosus.

Objective:To investigate the effect of human tumor suppressor folliculin (FLCN) on the expression of melanocyte chemokines (MC) mediated by immune factors in vitiligo.Methods:The MC of vitiligo patients that received autologous melanocyte transplantation in the Department of Dermatology, Hangzhou Third People′s Hospital from January to April 2019 were collected. The blister fluid of the white spot and the normal part was taken. Western blot was used to analyze the expression difference of MC and FLCN protein in normal, vitiligo patients and that induced by immune factors; FLCN shRNA lentivirus was constructed by shRNA and transfected into normal MC (FLCN shRNA MC) to interfere with the expression of silenced FLCN gene. The effect of immune factors on chemokines in FLCN shRNA MC was detected by ELISA.Results:The results of Western blot showed that FLCN protein was highly expressed in melanocytes of vitiligo patients, immune factors stimulated FLCN protein expression in normal melanocytes significantly increased ( t=1.27; P<0.001), chemokine CXCL10 and CCL20 also significantly increased ( t=104.53 and 60.21, respectively; P<0.001). The expression of FLCN in FLCN shRNA MC was significantly decreased ( F=1.95, P<0.001); and the high expression of CXCL10 and CCL20 induced by immune factors was significantly inhibited ( F=93.676 and 74.096, all P<0.001). Conclusions:Immune factors can stimulate the expression of CXCL10 and CCL20, which are closely related to vitiligo, while FLCN is a key protein involved in immune factors inducing melanocyte chemokine expression.

Objective:To verify Baveno VI criteria, Expanded-Baveno VI criteria, liver stiffness×spleen diameter-to-platelet ratio risk score (LSPS), and platelet count/spleen diameter ratio (PSR) in evaluating the severity value of esophageal varices (EV) in patients with non-cirrhotic portal hypertension (NCPH).Methods:111 cases of NCPH and 204 cases of hepatitis B cirrhosis who met the diagnostic criteria were included in the study. NCPH included 70 cases of idiopathic non-cirrhotic portal hypertension (INCPH) and 41 cases of nontumoral portal vein thrombosis (PVT). According to the severity of EV on endoscopy, they were divided into the low-bleeding-risk group (no/mild EV) and the high-bleeding-risk group (moderate/severe EV). The diagnostic value of Baveno VI and Expanded-Baveno VI criteria was verified to evaluate the value of LSPS and PSR for EV bleeding risk severity in NCPH patients. The t-test or Mann-Whitney U test was used to compare the measurement data between groups. Comparisons between counting data groups were performed using either the χ2 test or the Fisher exact probability method. Results:Considering endoscopy was the gold standard for diagnosis, the missed diagnosis rates of low/high bleeding risk EVs in INCPH/PVT patients with Baveno VI and Expanded-Baveno VI criteria were 50.0%/30.0% and 53.8%/50.0%, respectively. There were no statistically significant differences in platelet count (PLT), spleen diameter, liver stiffness (LSM), LSPS, and PSR between low-bleeding-risk and high-bleeding-risk groups in INCPH patients, and the area under the receiver operating characteristic curve (AUC) of LSPS and PSR was 0.564 and 0.592, respectively ( P=0.372 and 0.202, respectively). There were statistically significant differences in PLT, spleen diameter, LSPS, and PSR between the low and high-bleeding risk groups in PVT patients, and the AUCs of LSPS and PSR were 0.796 and 0.833 ( P=0.003 and 0.001, respectively). In patients with hepatitis B cirrhosis, the Baveno VI and Expanded-Baveno VI criteria were used to verify the low bleeding risk EV, and the missed diagnosis rates were 0 and 5.4%, respectively. There were statistically significant differences in PLT, spleen diameter, LSM, LSPS and PSR between the low-bleeding-risk and high-bleeding-risk groups ( P<0.001). LSPS and PSR AUC were 0.867 and 0.789, respectively ( P<0.05). Conclusion:Baveno VI and Expanded-Baveno VI criteria have a high missed diagnosis rate for EVs with low bleeding risk in patients with INPCH and PVT, while LSPS and PSR have certain value in evaluating EV bleeding risk in PVT patients, which requires further clinical research.

Objective:To investigate the clinical efficacy and prognosis of transjugular intrahepatic portosystemic shunt (TIPS) and drug combined with endoscopic treatment in patients with liver cirrhosis and esophagogastric variceal bleeding (EGVB).Methods:From January 2012 to December 2013, at the First Affiliated Hospital of Xi′an Jiaotong University, the data of 147 patients with liver cirrhosis and EGVB undergoing TIPS or drug combined with endoscopic treatment were retrospectively collected, with 87 cases in TIPS treatment group and 60 in drug combined with endoscopic treatment group.The 5 years follow-up data were analyzed, and the overall survival rates, rebleeding-free survival rates and hepatic encephalopathy-free survival rates at 6 weeks, 1 year, 2 years and 5 years after treatment of two groups were compared. Independent sample t test, Mann-Whitney U test, chi-square test, Fisher exact test, Z test, log-rank test and trend test were used for statistical analysis. Results:There were no significant differences in age, gender, etiology, Child-Pugh classification, initial liver function, coagulation function, liver ascites, previous history of hepatic encephalopathy, blood pressure and preoperative blood transfusion history between the TIPS treatment group and combination of drugs and endoscopy treatment group (all P>0.05). Forty-one patients died within 5 years, of which 20 (48.8%) died of rebleeding and 6 (14.6%) died of hepatic encephalopathy. There were no significant differences in 6-week, 1-year and 2-year overall survival rates between the TIPS group and drug combined with endoscopic treatment group (all P>0.05), however the 5-year overall survival rate of the TIPS treatment group was higher than that of the drug combined with endoscopic treatment group (78.4% vs. 63.2%), and the difference was statistically significant ( Z=2.06, P=0.048). The 6-week, 1-year, 2-year, 5-year rebleeding-free survival rates of the TIPS group were 97.7%, 96.5%, 88.9% and 70.9%, respectively, which were all higher than those of the drug combined with endoscopic treatment group (86.7%, 53.3%, 43.3% and 27.1%), and the differences were statistically significant ( Z=2.35, 6.39, 6.26 and 4.80, all P<0.05). There were no significant differences in hepatic encephalopathy-free survival rates at 6 weeks, 1 year and 2 years after treatment between the TIPS group and drug combined with endoscopic treatment group (all P>0.05), however the 5-year hepatic encephalopathy-free survival rate of the TIPS treatment group was lower than that of the drug combined with endoscopic treatment group (67.7% vs. 86.7%), and the difference was statistically significant ( Z=2.28, P=0.030). The lower the Child-Pugh classification, the higher the cumulative 5-year survival rate ( χ2=6.75, P<0.01). There was no statistically significant difference in the 5-year overall survival rate in patients with the same Child-Pugh classification between the TIPS group and the drug combined with endoscopic treatment group (all P>0.05). Conclusions:The efficacy of TIPS is better than that of the drug combined with endoscopic treatment in treating EGVB. Even the long-term risk of hepatic encephalopathy of TIPS is higher, the short-term, middle-term and long-term rebleeding rate are decreased. Patients with Child-Pugh grade C do not need to avoid TIPS when choosing the treatment, the earlier the TIPS used, the better survival benefit will be obtained.

Objective:To investigate the role of folliculin in apoptosis of and chemokine secretion by melanocytes mediated by interferon-γ (IFN-γ) .Methods:Normal primary melanocytes were isolated from circumcised foreskin tissues from a healthy male child, and primary vitiliginous melanocytes were isolated from normally pigmented suction-blistered epidermis from patients with vitiligo after suction blister epidermal grafting. Western blot analysis was performed to determine the folliculin protein expression in normal primary melanocytes, primary vitiliginous melanocytes and a human primary melanocyte line PIG1. PIG1 cells stimulated with 10 ng/ml IFN-γ for 48 hours served as induction group, and untreated PIG1 cells served as control group. Real-time quantitative RCR (qRT-PCR) was performed to determine the mRNA expression of folliculin, autophagy-related microtubule-associated protein 1 light chain 3 (LC3) -Ⅱ and Beclin genes, and Western blot analysis to determine the protein expression of folliculin, Beclin1 and LC3Ⅱ/Ⅰ, as well as phosphorylation levels of adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) in the above cells. Furthermore, the melanocytes stimulated with 10 ng/ml IFN-γ for 48 hours were divided into several groups: negative control group infected with an empty lentiviral vector, folliculin inhibition group infected with a folliculin-inhibiting lentivirus, autophagy enhancement group infected with a folliculin-inhibiting lentivirus followed by 2-hour treatment with a mTOR inhibitor, autophagy inhibition group infected with a folliculin-inhibiting lentivirus followed by 2-hour treatment with an AMPK inhibitor. Then, flow cytometry was conducted to detect apoptosis of PIG1 cells, and enzyme-linked immunosorbent assay to measure the concentration of chemokines CXCL10 and CCL20 in the culture supernatant of PIG1 cells in the above groups. Measurement data were compared among multiple groups by using one-way analysis of variance, and multiple comparisons were carried out by using least significant difference- t test. Results:The relative protein expression level of folliculin significantly differed among the normal primary melanocytes (0.850 ± 0.120) , primary vitiliginous melanocytes (1.507 ± 0.170) and PIG1 cells (0.697 ± 0.130; F = 50.09, P < 0.001) , and was significantly higher in the primary vitiliginous melanocytes than in the normal primary melanocytes and PIG1 cells ( t = 4.06, 5.89, respectively, both P < 0.01) . Compared with the control group, the induction group showed significantly increased relative mRNA and protein expression levels of folliculin (both P < 0.01) , but significantly decreased relative mRNA and protein expression levels of LC3Ⅱ and Beclin (all P < 0.01) ; moreover, the induction group showed significantly decreased LC3Ⅱ/Ⅰ levels (0.72 ± 0.02) and AMPK phosphorylation levels (0.714 ± 0.023) in the PIG1 cells compared with the control group (1.13 ± 0.02, 1.176 ± 0.002, t = 7.34, 6.67, respectively, both P < 0.01) , but significantly increased mTOR phosphorylation levels (1.051 ± 0.023) compared with the control Group (0.451 ± 0.016, t = 3.81, P = 0.009) . There were significant differences in the PIG1 cell apoptosis rate and concentrations of CXCL10 and CCL20 among the control group, induction group and other treatment groups (all P < 0.001) ; specifically, the PIG1 cell apoptosis rate and concentrations of CXCL10 and CCL20 were significantly higher in the induction group than in the control group, lower in the folliculin inhibition group than in the negative control group, lower in the autophagy enhancement group than in the folliculin inhibition group, and higher in the autophagy inhibition group than in the folliculin inhibition group (all P < 0.05) . Conclusions:Folliculin is highly expressed in vitiliginous melanocytes. Folliculin expression and downstream signaling pathways are regulated by IFN-γ, and folliculin may participate in IFN-γ-mediated melanocyte apoptosis and chemokine secretion via regulating autophagy.

Objective:To investigate the effect of ultrasound-guided transversus abdominis plane (TAP) block combined with iliohypogastric/ilioinguinal TAP block in high-risk elderly patients undergoing inguinal hernia repair.Methods:Sixty male patients undergoing elective inguinal hernia repair, aged ≥70 years, BMI 18-23 kg/m 2, ASAⅢ-Ⅳ grade, were randomly divided into two groups: ultrasound-guided lateral TAP block combined with iliohypogastric/ilioinguinal TAP block group (combined group) and lateral TAP block group (lateral group), with 30 cases in each group. In the combined group, the injection concentration of 0.375% ropivacaine 20 ml was at the iliohypogastric/ilioinguinal TAP puncture site and the lateral TAP puncture site was also 20 ml, and the lateral group only injected 0.375% 20 ml at the lateral TAP puncture site. The Visual Analogue Scale (VAS) of the two groups were compared at surgical skin incision (T 1), opening of external oblique aponeurosis (T 2), free hernia sac (T 3), separation of preperitoneal space and patch placement (T 4), suture of transverse abdominal fascia (T 5), suture of external oblique abdominal aponeurosis (T 6) and skin incision are closed (T 7); The VAS were compared during rest and activity at 2, 4, 6, 8, 12 and 24 hours after surgery. The cumulative consumption of relief analgesics was compared. Results:Compared with the lateral group, the VAS of the combined group during T 3-T 5 was significantly lower ( P<0.05). The VAS score at 4, 6 and 8 hours after operation in the combined group was also significantly lower ( P<0.05). There was no statistical significance in VAS score at rest between the two groups 24 h after operation ( P>0.05). The cumulative consumption of relief analgesics in the combined group was lower ( P<0.05). The difference of adverse events between the two groups was not statistically significant ( P>0.05). Conclusion:In high-risk elderly patients, ultrasound-guided transverse abdominal muscle plane two-point block can be used as a safe alternative method of intraoperative analgesia.