[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

Objective To establish a stable and reliable sepsis model of rat after liver transplantation (LT) for clinical translational research and analyze its characteristics. Methods The "two-sleeve method" was used to establish the in situ LT model of SD rats, and the sepsis model was constructed through cecal ligation and puncture (CLP) at 3 d after the operation. SD rats were randomly divided into 3 groups: sham operation group (Sham group), LT group, and LT + CLP group, with 6 rats in each group. The changes in body weight, rectal temperature and survival rate were compared, and the sepsis score was used for evaluation. The levels of blood biochemical indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Urea), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH)] and inflammatory factors [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α] in each group were detected, and the pathological changes and cell apoptosis in different organs were observed. Results Compared with the Sham group, the body weight of the LT group and LT + CLP group decreased (all P<0.05). The rectal temperature of the LT + CLP group showed a continuous downward trend after the operation, the sepsis score increased sharply after the operation, and the survival rate dropped to 16.7%, and the differences between the Sham group, LT group and LT + CLP group were statistically significant (all P<0.05). The levels of ALT, AST, Urea, Cr, CK, LDH, and serum IL-1β, IL-6, IL-10 and TNF-α in the LT + CLP group were higher than those in the Sham group and LT group rats within 72 hours after the operation(all P<0.05). The pathological examination of the LT + CLP group showed severe tissue structure destruction, necrosis and infiltration of inflammatory cells in multiple organs, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed an increased level of cell apoptosis in multiple organs. Conclusions Using liver transplantation combined with CLP, a stable animal model of liver transplantation infection is successfully established, which exhibits a high mortality rate, significant multi-organ damage and intense inflammatory response, providing an ideal animal model for transplantation infection research.

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 explore the genetic basis for a girl with primary microcephaly and growth retardation.Methods:A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278).Results:DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c. 2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. Conclusion:Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Objective:To explore the predictive value of dual-energy CT lumbar quantitative measurement combined with serum bone alkaline phosphatase (BALP), osteocalcin (BGP), and β-type I collagen carboxy-terminal peptide ( β-CTx) for the risk of fractures in patients with osteoporosis. Methods:A total of 90 patients with osteoporosis who underwent dual-energy CT lumbar quantitative detection at the First People’s Hospital of Shangqiu from Jan. 2020 to Jan. 2023 were selected as the research subjects. According to the occurrence of fractures within one year of follow-up, the patients were divided into the fracture group ( n=36) and the non-fracture group ( n=54). The clinical data, dual-energy CT lumbar quantitative parameters, and serum BALP, BGP, and β-CTx levels of the two groups were compared. Logistic multivariate regression analysis was used to analyze the risk factors for fractures in patients with osteoporosis, and the receiver operating characteristic (ROC) curve was used to analyze the predictive value of dual-energy CT lumbar quantitative parameters combined with serum BALP, BGP, and β-CTx for fractures in patients with osteoporosis. Results:There were no statistically significant differences in gender, age, body mass index (BMI), smoking history, drinking history, or bone marrow CT value parameters between the fracture group and the non-fracture group ( χ2=0.66, t=1.86, t=1.59, χ2=0.19, χ2=0.98, t=0.40, all P > 0.05). However, there were statistically significant differences in the history of fragility fractures, regular calcium supplementation, lumbar bone mineral density (BMD), calcium CT value, mixed energy image CT value, calcium concentration, fat fraction, BALP, BGP, and β-CTx ( χ2=9.73, χ2=4.17, t=3.14, t=7.06, t=7.92, t=6.50, t=3.26, t=8.12, t=12.66, t=11.37, all P < 0.05). Logistic multivariate regression analysis showed that the history of fragility fractures ( OR=1.863, P=0.023), regular calcium supplementation ( OR=1.728, P=0.031), fat fraction ( OR=1.685, P=0.009), BALP ( OR=1.815, P=0.002), BGP ( OR=1.605, P=0.003), and β-CTx ( OR=1.636, P < 0.001) were risk factors for fractures in patients with osteoporosis, while lumbar bone BMD ( OR=0.456, P=0.025), calcium CT value ( OR=0.486, P=0.005), mixed energy image CT value ( OR=0.490, P < 0.001), and calcium concentration ( OR=0.509, P=0.010) were protective factors. The ROC curve showed that the sensitivity of dual-energy CT lumbar quantitative measurement parameters combined with serum BALP, BGP, and β-CTx in predicting fractures in patients with osteoporosis was 94.68%, the specificity was 92.16%, the Youden index was 0.868, the area under the curve (AUC) was 0.947, and the 95% confidence interval ( CI) was 0.905 to 0.982. Conclusion:Dual-energy CT lumbar quantitative parameters and serum BALP, BGP, and β-CTx levels have certain predictive value for the risk of fractures in patients with osteoporosis, and the combined prediction value is higher.

Objective:To analyze the therapeutic effect of a virtual reality (VR)-based accommodation training device on accommodative excess visual fatigue.Methods:A case-control study was conducted.A total of 20 normal subjects (20 eyes) and 20 patients with accommodative excess visual fatigue (20 eyes) were recruited at Zhongshan Ophthalmic Center, Sun Yat-sen University between January and December 2022.The study consisted of two phases.In the first phase, the effect of watching videos with VR glass on the subjects' subjective and objective visual function was evaluated.Normal subjects wore VR device to watch a 2D video for 30 minutes, and assessments were performed before and after viewing.These assessments included binocular accommodation/convergence function (accommodation response, accommodative convergence to accommodation ratio [AC/A]), tear film function (first tear film break-up time), subjective symptoms (visual fatigue score), and basic visual health parameters including best corrected visual acuity (BCVA) and intraocular pressure (IOP).In the second phase, the improvement in subjective and objective visual fatigue metrics with the VR-based accommodation training device was investigated.Patients with visual fatigue were divided into a traditional training group using traditional flipper lenses and a VR training group using the VR accommodation training device, with 10 eyes in each group.The effects of the VR accommodation training device on indicators such as accommodative sensitivity, accommodation response, convergence function, visual fatigue score, acceptability score, system usability score, BCVA, and IOP were evaluated and compared between the two groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.IIT2021007).Written informed consent was obtained from each subject.Results:In normal subjects, there was no statistically significant difference in first tear film break-up time, distance phoria, near phoria, AC/A, accommodative response, BCVA, or IOP before and after 30 minutes of continuous viewing of 2D video using VR glass ( t=1.155, 1.360, 4.479, 1.979, -1.249, -3.017, 2.211; all P>0.05).The visual fatigue score remained unchanged at (1.00±0.00) points before and after viewing.Among the subjects with visual fatigue, there were statistically significant differences in binocular accommodative sensitivity, dominant eye accommodative sensitivity, and BCVA before and after using the VR accommodation training device ( F=8.693, 4.078, 4.942; all P<0.05).Ocular accommodation sensitivity at 8 weeks after training was improved compared with 1 week after training, and BCVA at 4 weeks after training was improved compared with before training, and the differences were statistically significant (both P<0.05).In the VR training group, the average tear film break-up time, first tear film break-up time, and BCVA increased and the visual fatigue score decreased compared with before training, the differences were statistically significant (all P<0.05).In the traditional training group, the accommodation sensitivity of the dominant eye increased after training compared with before training, with a statistically significant difference ( P<0.05). Conclusions:Watching 2D videos with VR glass for 30 minutes does not induce subjective or objective symptoms of visual fatigue.The VR-based accommodation training paradigm effectively improves accommodative sensitivity and alleviates subjective symptoms of visual fatigue in individuals with accommodative excess visual fatigue.

Objective To investigate the mechanism by which apelin inhibits the transition from acute kidney injury(AKI)to chronic kidney disease(CKD).Methods Human proximal tubular epithelial cells were cultured in vitro and divided into control,cisplatin,cisplatin+apelin,cisplatin+apelin+Sirt3 siRNA,and apelin groups.Cells were transfected with Sirt3 siRNA and incubated with a medium containing cisplatin(10 μmol/L)and/or apelin-13(1 μmol/L).Mitochondrial morphology was observed using MitoTracker? probes;mito-chondrial membrane potential was detected using the JC-1 assay kit;and the expression of the fibrogenic cytokine,transforming growth factor β1(TGF-β1)was measured by Western blotting.Forty 10-week-old male C57BL/6J mice were divided into control,cisplatin,cisplatin+apelin,cisplatin+apelin+Sirt3 knockdown,and empty adenovirus groups,with eight mice per group.Except for the control and empty adenovirus groups,all the other groups were intraperitoneally injected with cisplatin(20 mg/kg)to establish the AKI model.The cis-platin+apelin group was intraperitoneally injected with apelin-13(0.1 μg·kg-1·d-1);the control group was injected with an equal volume of saline;the cisplatin+apelin+Sirt3 knockdown group was injected with Sirt3 knockdown adenovirus(2 × 109 pfu/mL)via the tail vein and intraperitoneal injection of apelin-13(0.1 μg·kg-1·d-1);and the empty adenovirus group was injected with adenovirus(2 × 109 pfu/mL)via the tail vein.The mice were sacrificed after 2 weeks.Kidney fibrosis was assessed by Masson's trichome staining.Type Ⅰ collagen(Col-Ⅰ)expression was observed by immunohistochemical staining.Plasma creatinine(Cr)and blood urea nitrogen(BUN)levels were measured by ELISA.Results In vitro experiments showed that,compared with the control group,the cisplatin group exhibited reduced mitochondrial fluorescence staining,decreased mitochondrial membrane potential,and increased TGF-β1 expression(all P＜0.05).Compared with the cisplatin group,the cisplatin+apelin group showed increased fluorescence staining,elevated mitochondrial membrane potential,and reduced TGF-β1 expression(all P＜0.05);however,these effects were counteracted after Sirt3 siRNA transfection.In vivo experiments showed that,compared with the control group,the cisplatin group exhibited significant renal tubular atrophy and interstitial fibrosis,increased Col-Ⅰ positive expression,and elevated plasma Cr and BUN levels(all P＜0.05).Compared with the cisplatin group,the cisplatin+apelin group showed a significant improvement in all the above indicators(all P＜0.05).Compared with the cisplatin+apelin group,the cisplatin+apelin+Sirt3 knockdown group showed a significant reduction in the renal protective effects of apelin.Conclusion The polypeptide apelin inhibits the transition from AKI to CKD by regulating Sirt3 expression to maintain mitochondrial structure and function,which can reduce renal fibrosis and improve renal function.