Background/Aims: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). Methods: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. Results: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. Conclusions The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

Humans ; Angina, Stable ; COVID-19 ; Risk Factors ; Patients

ObjectiveEstablish an animal model of preeclampsia in goats, collect data on various physiological indicators and maternal biological characteristics of the disease model to compare with clinical feature of the disease in humans, provide reference for the prevention and treatment of preeclampsia in humans.Methods Twenty-three goats bred in Chongming district were divided into three groups: Control group, no surgical procedure was performed on animals of this group; sham group, ewes in this group underwent the sham operation on the 100±5th day of gestation, and only the uterine artery was exposed and dissociated; surgical group, a silver vascular clamp was clipped on one side of the uterine body artery of the ewe to narrow the inner diameter of the artery at the same gestation period (100±5) days. Heart rate and hindlimb blood pressure were continuously monitored in control and surgical ewes from 100 to 140 d of gestation, and blood flow data within the lateral branches of the uterine arteries of ewes in the sham group were collected using a hemodynamometer in combination with a hemodynamic probe and an animal physiological signal collector, as well as changes in blood flow within the uterine arteries in the lateral branches of the uterine arteries of the surgical group before and after placement of vascular clips in the surgical ewes. At the expected date of delivery, jugular vein blood was taken from ewes for routine blood test, creatinine, urea nitrogen, and blood ion analysis; urine was also collected from ewes in each group for analysis of urinary protein and urinary creatinine. All experimental groups were subjected to cesarean section on the 140±5th day of gestation in ewes, and then liver, kidney, uterus and placenta tissues were taken from ewes in each group and stained with HE for pathological observation. Results After 15 minutes of preeclampsia modeling surgery, blood flow volume remained stable in the vessel stenosis segment and the volume differential was relatively reduced in comparison to the control group and sham group (P＜0.05，P＜0.01). Compared with the control group, the ewes in the surgical group showed prenatal changes such as increased serum osmolality, decreased hemoglobin, increased blood glucose and urea nitrogen values, as well as increased levels of calcium, sodium, and chloride ions (all P<0.05) and proteinuria, with urinary creatinine and urinary protein-creatinine ratios were significantly higher than those in the control group and sham group (all P<0.05). The elastic lamina of the uterine body arteries on the operated side of the animals in the surgical group was thicker than that on the opposite side, but the structure was loose. The placenta on the operated side showed pathological changes such as cell interstitial swelling and inflammatory cell infiltration. The above physiological index characteristics were more consistent with the clinical features of human preeclampsia disease.Conclusion In this experiment, we successfully constructed a goat preeclampsia model and obtained data on relevant physiological indexes of this model, which further verified the correlation between preeclampsia disease and uterine artery lesions.

Objective:To investigate risk factors of arrhythmia in elderly patients with early lung cancer after thoracoscopic pulmonary resection to construct a prediction model.Methods:Two hundreds and twenty elderly patients with early lung cancer after thoracoscopic pulmonary resection were retrospectively chosen in the period from January 2017 to January 2023 in Guang'an People's Hospital of Sichuan Province. The occurrence of arrhythmia was calculated, and the clinical data of patients with arrhythmia and those without arrhythmia were compared. Logistic regression was employeed to analyze the independent influencing factors of arrhythmia in elderly patients with early lung cancer after thoracoscopic pneumonectomy. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of regression model on arrhythmia after thoracoscopic pneumonectomy in elderly patients with early lung cancer.Results:Forty-one of 220 (18.64%) elderly patients with early lung cancer treated by thoracoscopic pneumonectomy had arrhythmia. There were statistically significant differences between patients with arrhythmia and patients without arrhythmia in age ( χ2=17.76, P<0.001), combined with essential hypertension ( χ2=21.06, P<0.001), forced expiratory volume in one second as a percentage of predicted value (FEV 1%) ( χ2=17.88, P<0.001), left atrium anterior-and-posterior diameter ( χ2=37.82, P<0.001), operation type ( χ2=27.09, P<0.001) and postoperative constipation ( χ2=18.25, P<0.001). The results of multivariate analysis showed that age>75 years old ( OR=22.17, 95% CI: 3.78-130.11, P=0.001), combined with essential hypertension ( OR=26.55, 95% CI: 3.99-176.95, P=0.001), FEV 1%≤70% ( OR=6.20, 95% CI: 1.37-28.11, P=0.018), left atrium anterior-and-posterior diameter>40 mm ( OR=10.84, 95% CI: 2.24-52.45, P=0.003), thoracoscopic lobectomy ( OR=7.07, 95% CI: 1.62-30.80, P=0.009), and postoperative constipation ( OR=79.97, 95% CI: 11.87-538.83, P<0.001) were all independent risk factors for arrhythmia after thoracoscopic pulmonary resection in elderly patients with early lung cancer. A prediction model was established for statistically significant indicators in multivariate analysis, ln ( P/1- P) =-7.89+3.10×age+3.28×combined with essential hypertension+1.82×FEV 1%+2.38×left atrium anterior-and-posterior diameter+1.96×operation type+4.38×postoperative constipation ( P was the prediction probability of P value in regression model). ROC curve analysis showed that the area under the curve (AUC) of predict arrhythmia after thoracoscopic pulmonary resection in elderly patients with early lung cancer were 0.64, 0.71, 0.68, 0.74, 0.76, 0.87 and 0.98, respectively. The Yoden index was 27.29%, 42.28%, 34.92%, 47.42%, 73.63%, 50.97% and 91.97%, respectively. Conclusion:Age>75 years old, combined with essential hypertension, FEV 1%≤70%, left atrium anterior-and-posterior diameter>40 mm, thoracoscopic lobectomy and postoperative constipation are all independent risk factors for arrhythmia after thoracoscopic pulmonary resection in elderly patients with early lung cancer. Nomogram model based on the above risk factors has high efficacy in predicting arrhythmia occurance after thoracoscopic pulmonary resection.

The clinical data of patients with hepatocellular carcinoma who underwent anatomical hepatectomy at the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University from June 2021 to January 2022 were retrospectively analyzed. Of 4 patients, there were 3 males and 1 female, aged (52.0±3.7) years. These patient underwent anatomical hepatectomy using the " target territory hepatic artery dye-injection" method. There were 2 patients with right hemi liver tumors with portal vein tumor thrombus, and 1 patient with a right anterior section tumor which involved the ventral segment of right anterior branch of portal vein. One patient had a left hemi liver tumor with portal vein tumor thrombus. The surgical operations were right hemihepatectomy combined with thrombectomy of portal vein in 2 patients, right anterior sectionectomy in 1 patient, and left hemihepatectomy combined with thrombectomy of portal vein in 1 patient. There were no postoperative complications including bile fistula or bleeding. The "Target territory hepatic artery dye-injection" method could be used in appropriate by selected patients.

Objective:To investigate the effect of tidal volume (Vt DI) on pulse pressure variation (ΔPP DI) during deep inspiration maneuvers in spontaneously breathing patients with sepsis and to test if adjusting ΔPP DI by Vt DI can further improve its ability in predicting fluid responsiveness (FR). Methods:Spontaneously breathing, nonintubated sepsis or septic shock patients who were admitted to the Intensive Care Unit of the Characteristic Medical Center of Chinese People's Armed Police Force and Nanjing Gaochun People's Hospital were prospectively enrolled from October 2017 to October 2019. Volume expansion (VE) was performed by infusing 500 mL saline over 20 min. Prior to VE, measurements including pulse pressure variation and tidal volume were obtained during quiet spontaneous breathing (ΔPP TB and Vt TB, respectively) and during the deep inspiration maneuver (ΔPP DI and Vt DI, respectively). Patients were classified as responders if stroke volume (SV) increased ≥ 15% after VE, otherwise non-responders. Multiple linear regression analysis was conducted to investigate the correlation of ΔPP DI with Vt DI and VE-induced percentage changes in SV (ΔSV). Receiver operating characteristic (ROC) curve analysis and the gray zone approach were used to assess the ability of each index to predict FR. Changes in gray zone limits according to the cost ratio (R = cost[false positive (FP)]/cost[false negative (FN)]) were also evaluated. Results:Of the included 31 patients, 17 were responders. There was no significant difference in ΔPP TB between fluid responders and non-responders ( P>0.05), whereas ΔPP DI was significantly higher in responders than in non-responders [(19.1±7.4)% vs (11.2±4.5)%; P=0.001]. The area under the ROC curve (AUC) of ΔPP DI predicted FR was 0.832, sensitivity of 76.47% and specificity of 71.43%, which was significantly higher than ΔPP TB (AUC=0.580, sensitivity of 47.06% and specificity of 71.43%; P<0.05). Multiple linear regression analysis showed that both Vt DI and ΔSV were independently associated with ΔPP DI ( P<0.01), the AUC of ΔPP DI adjusted by Vt DI was signigicantly higher than that of ΔPP DI alone ( P=0.03). Among the ΔPP TB, ΔPP DI and ΔPP DI/Vt DI, ΔPP DI/Vt DI had the narrowest gray zone (12.7-14.5) for the normal fluid policy (R=1), which only included 19% of the patients. When applying "restrictive" fluid management (R=2), the gray zone for ΔPP DI/Vt DI was 12.8-14.5 and included only 2 patients (6.5%). Conclusions:In spontaneously breathing, nonintubated patients with sepsis or septic shock, the ΔPP value obtained during the deep inspiration maneuver predicts FR with moderate accuracy. Given the close correlation between Vt DI and ΔPP DI, ΔPP DI adjusted by Vt DI performs better than ΔPP DI alone in predicting FR.

OBJECTIVES: At present, removable partial denture is still one of the main restoration methods for dentition defects. However, the trend for digital partial denture is becoming more and more obvious in the field of oral repair. However, there are relatively few studies on digital removable partial denture. The aim of this study is to investigate the effects of 3 processing technologies (precision casting, digital cutting, and 3D printing) on the fitness for the clasps of cobalt chromium alloy and pure titanium removable partial denture, and to provide a theoretical basis for the clinical application of digital removable partial denture. METHODS: Clasps of Co-Cr alloy and pure titanium were produced by 3 different processing technologies (precision casting, digital cutting, and 3D printing). There are 6 groups, including a casting pure titanium group, a casting cobalt chromium group, a cutting pure titanium group, a cutting cobalt chromium group, a printing pure titanium group, and a printing cobalt chromium group ( RESULTS: There was no statistical difference in fitness between the casting pure titanium group and the casting cobalt chromium group ( CONCLUSIONS The cobalt chromium alloy and pure titanium clasps made by precision casting, digital cutting, and 3D printing have good fitness. Under the same process, there is no significant difference between cobalt chromium alloy and pure titanium clasps. The 3D printing pure titanium clasps have better fitness than casting pure titanium and cutting pure titanium clasps, which meet the needs of clinical application.
Chromium Alloys ; Cobalt ; Denture, Partial, Removable ; Titanium

Objective:To investigate the causes of immune failure in the population with high vaccination rate of measles and rubella vaccine in Beijing by detecting the IgG antibody affinity in suspected cases of measles and rubella.Methods:Serum samples of 276 suspected cases of measles and rubella were tested for IgM and IgG antibodies by enzyme-linked immunosorbent assay (ELISA). The affinity of IgG antibody was detected, and the relative affinity index was calculated.Results:Among the 276 suspected cases, 104 were measles and 108 were rubella. Six measles cases had vaccination history and were caused by primary immunization failure ( n=3) and secondary immunization failure ( n=3). Twelve rubella cases had vaccination history and were due to primary immunization failure ( n=4) and secondary immunization failure ( n=8). Specific high-affinity antibodies were detected in nine measles cases and seven rubella cases without vaccination history, which indicated that these cases were reinfected. In the cases without measles or rubella, other pathogenic infections including mixed infections were detected, which were mainly caused by EB virus. Conclusions:Both primary and secondary immunization failure occurred in the population with immunization history. Reinfection was found in the patients who had not received vaccination against measles or rubella. Other pathogenic infections were existed among the cases without measles or rubella. Thus, misdiagnosis was responsible for the increased proportion of measles and rubella patients with immunization history in suspected cases in recent years. Full-course vaccination was conducive to produce high-affinity antibodies against measles and rubella. A supplementary vaccination campaign should be launched to consolidate the immune barrier against measles and rubella in key population or high-risk population, aiming to block the circulation of measles virus and achieve the goal of eliminating measles.

Organic anion transporter 3 (OAT3) plays a vital role in removing a broad variety of anionic drugs from kidney, thus avoiding their possible toxicity in the body. In the current study, we investigated the role of insulin-like growth factor 1 (IGF-1) in the regulation of OAT3. We showed that IGF-1 induced a dose- and time-dependent increase in OAT3 transport activity, which correlated well with an increase in OAT3 expression. The IGF-1-induced increase in OAT3 expression was blocked by protein kinase A (PKA) inhibitor H89. Moreover, IGF-1 induced an increase in OAT3 phosphorylation, which was also blocked by H89. These data suggest that the IGF-1 modulation of OAT3 occurred through PKA signaling pathway. To further confirm the involvement of PKA, we treated OAT3-expressing cells with PKA activator Bt2-cAMP, followed by examining OAT activity and phosphorylation. We showed that OAT3 activity and phosphorylation were much enhanced in Bt2-cAMP-treated cells as compared to that in control cells. Finally, linsitinib, an anticancer drug that blocks the IGF-1 receptor, abrogated IGF-1-stimulated OAT3 transport activity. In conclusion, our study demonstrated that IGF-1 regulates OAT3 expression and transport activity through PKA signaling pathway, possibly by phosphorylating the transporter.

Objective:To analyze the molecular epidemiology and virulence characteristics of polymyxin-resistant Klebsiella pneumoniae ( K. pneumoniae). Methods:From 2011 to 2016, 1 376 strains of K. pneumoniae were isolated from various clinical specimens of hospitalized patients in First Affiliated Hospital of Wenzhou Medical University. Agar dilution method was used to screen out the polymyxin-resistant strains.Polymerase chain reaction (PCR) was used to detect the genes related to polymyxin resistance, and real-time fluorescence quantitative PCR was used to detect the relative mRNA expression level of drug resistant genes. Pulsed-field gel electrophoresis, multilocus sequence typing and Galleria mellonella larvae infection model were performed to analyze the molecular epidemiological and virulent characteristics. Results:A total of 14 strains (1.02%) of polymyxin-resistant K. pneumoniae were detected among 1 376 K. pneumoniae isolates. Subsequent sequencing identified mutations leading to amino-acid changes (K2E, F28C) in MgrB of 10 isolates and D150G in PhoQ of nine isolates, and genes such as mcr and crrB were not detected in all drug-resistant strains. Compared with standard strains, the relative expression levels of pmrH and pmrD mRNA of these drug resistant strains were increased. Analysis of the molecular epidemiology indicated that the 14 drug-resistant strains were divided into nine clones. Galleria mellonella larvae infection model revealed polymyxin-resistant K. pneumoniae isolates had higher virulence. Conclusions:Polymyxin-resistant K. pneumoniae has mutations in mgrB and phoQ genes, and mgrB mutation may play a key role in the change of virulence profiles. The homology among the polymyxin-resistant K. pneumoniae stains in this study is low.