Therapeutic drug monitoring of polymyxin B cerebrospinal fluid concentrations in patients with carbapenem-resistant Gram-negative bacteria-induced central nervous system infection.

OBJECTIVES: Central nervous system (CNS) infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) present a major health and economic burden worldwide. This multicentre prospective study aimed to assess the feasibility and usefulness of CSF therapeutic drug monitoring (TDM) after intrathecal/intraventricular administration of polymyxin B in patients with CNS infections. METHODS: Forty-two patients treated with intrathecal/intraventricular administration of polymyxin B against CR-GNB-induced CNS infections were enrolled. CSF trough level (Cmin) was collected beginning on Day 2 post-polymyxin B initiation and thereafter. The primary outcomes were clinical cure and 28-day all-cause mortality. RESULTS: All patients started with intrathecal/intraventricular administration of polymyxin B at a dose of 5 g/day, corresponding to a median CSF Cmin of 2.93 mg/L (range, 0.21-25.74 mg/L). Clinical cure was 71.4%, and the median CSF Cmin of this group was higher than that of clinical failure group [3.31 (IQR, 1.73-5.62) mg/L versus 2.25 (IQR, 1.09-4.12) mg/L; P = 0.011]. In addition, with MICs ≤ 0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (P = 0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin. CONCLUSIONS: After intrathecal/intraventricular administration of polymyxin B, CSF concentrations fluctuated considerably inter- and intra-individual. Polymyxin B CSF Cmin above 2.0 mg/L was associated with clinical cure when MICs were ≤ 0.5 mg/L, and the feasibility of TDM warrants additional clinical studies.

Doubly robust proximal synthetic controls.

To infer the treatment effect for a single treated unit using panel data, synthetic control (SC) methods construct a linear combination of control units' outcomes that mimics the treated unit's pre-treatment outcome trajectory. This linear combination is subsequently used to impute the counterfactual outcomes of the treated unit had it not been treated in the post-treatment period, and used to estimate the treatment effect. Existing SC methods rely on correctly modeling certain aspects of the counterfactual outcome generating mechanism and may require near-perfect matching of the pre-treatment trajectory. Inspired by proximal causal inference, we obtain two novel nonparametric identifying formulas for the average treatment effect for the treated unit: one is based on weighting, and the other combines models for the counterfactual outcome and the weighting function. We introduce the concept of covariate shift to SCs to obtain these identification results conditional on the treatment assignment. We also develop two treatment effect estimators based on these two formulas and generalized method of moments. One new estimator is doubly robust: it is consistent and asymptotically normal if at least one of the outcome and weighting models is correctly specified. We demonstrate the performance of the methods via simulations and apply them to evaluate the effectiveness of a pneumococcal conjugate vaccine on the risk of all-cause pneumonia in Brazil.

Peripheral nerve injury associated with JEV infection in high endemic regions, 2016-2020: a multicenter retrospective study in China.

Previously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain-Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016-2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1-34]; adults, 25 years [range, 0-183]) and intensive care unit (children, 16 years [range, 1-30]; adults, 17 years [range, 0-102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

Prediction of pulmonary infection in patients with severe myelitis by NPAR combined with spinal cord lesion segments.

Objectives: To investigate the risk factors of pulmonary infection in patients with severe myelitis and construct a prediction model. Methods: The clinical data of 177 patients with severe myelitis at admission from the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were retrospectively analyzed. The predicting factors associated with pulmonary infection were screened by multivariate logistic regression analysis, and the nomogram model was constructed, and the predictive efficiency of the model was evaluated, which was verified by calibration curve, Hosmer-Lemeshow goodness-of-fit test and decision curve analysis. Results: Of the 177 patients with severe myelitis, 38 (21.5%) had pulmonary infection. Multivariate logistic regression analysis showed that neutrophil percentage to albumin ratio (NPAR) (OR = 6.865, 95%CI:1.746-26.993, p = 0.006) and high cervical cord lesion (OR = 2.788, 95%CI:1.229-6.323, p = 0.014) were independent risk factors for pulmonary infection, and the combined nomogram could easily predict the occurrence of pulmonary infection, with a C-index of 0.766 (95% CI: 0.678-0.854). The calibration curve, Hosmer-Lemeshow goodness-of-fit test (χ2 = 9.539, p = 0.299) and decision curve analysis showed that the model had good consistency and clinical applicability. Conclusion: The nomogram model constructed based on NPAR combined with high cervical cord lesion at admission has good clinical application value in predicting pulmonary infection in patients with severe myelitis, which is conducive to clinicians' evaluation of patients.

Nomogram to Predict the Prognosis of Oligodendroglioma Patients Undergoing Postoperative Adjuvant Chemoradiotherapy.

OBJECTIVE: The aim of this study was to develop a prognostic nomogram for predicting the prognosis of oligodendroglioma patients receiving combined chemoradiotherapy (CRT) after surgery. METHODS: The study used data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The patients were randomly divided into a development cohort (700 patients) and a validation cohort (244 patients) in a 7:3 ratio. The Cox hazards regression model was used to identify predictors, and a nomogram was constructed to visualize the prognosis. The performance of the prognostic nomogram was evaluated using the consistency index (C-index), clinical net benefit, and calibration. RESULTS: The nomogram included 5 variables: age, marital status, tumor size, site of lesions, and surgery type. The C-index of the training set and validation set were 0.77 and 0.68, respectively. The calibration plots showed that the nomogram was in good agreement with the actual observation. The clinical decision curve indicated that the nomogram had a good clinical net benefit in oligodendroglioma patients receiving CRT after surgery. CONCLUSIONS: This study established and verified a prognostic nomogram for a large cohort of oligodendroglioma patients receiving CRT after surgery based on the SEER database. The nomogram may help clinicians provide personalized treatment services and clinical decisions for patients.

The triglyceride glucose index predicts short-term mortality in non-diabetic patients with acute heart failure.

BACKGROUND: The triglyceride glucose index (TyG) has previously been considered a reliable indicator of insulin resistance (IR) and an independent prognostic predictor in heart failure (HF). OBJECTIVES: To clarify the association between the TyG and short-term death in non-diabetic patients admitted for acute heart failure (AHF). MATERIAL AND METHODS: We examined 886 out of 1620 consecutive AHF patients who were admitted to Shunde Hospital, Southern Medical University, Foshan, China, from June 1, 2014, to June 1, 2022. The median of the patientsf TyG values was used to divide them into 2 groups. The following formula was used to calculate the TyG: ln [fasting triglycerides (mg/dL) ~ fasting glucose (mg/dL)/2]. The data on all-cause mortality of AHF patients during their hospital stay were collected. The 30-day Enhanced Feedback for Effective Cardiac Treatment (EFFECT) death risk score was used to assess the risk of death. RESULTS: The TyG level was positively correlated with a poor AHF prognostic marker (N-terminal B-type natriuretic peptide (NT-proBNP)) (D = 0.207, p < 0.001) and negatively correlated with a protective marker (serum albumin) (D = .0.43, p < 0.001). Higher TyG values were associated with an elevated EFFECT score and hospital mortality (p < 0.001). According to multivariate logistic regression analysis, higher TyG levels raised the risk of death in hospital (odds ratio (OR) = 1.73; 95% confidence interval (95% CI): 1.03.3.27; p = 0.031) after adjusting for multiple variables, including age, EFFECT score and NT-proBNP. The TyG had a greater area under the receiver operating characteristic (ROC) curve (AUC: 0.688) for predicting hospital death compared to NT-proBNP (AUC: 0.506). CONCLUSIONS: Our findings show that the TyG is associated with the short-term mortality rate of non-diabetic patients admitted to the hospital for AHF. The TyG testing could be a useful prognostic indicator for these patients.

Moxibustion enables protective effects on rheumatoid arthritis-induced myocardial injury transforming growth factor beta1 signaling and metabolic reprogramming.

OBJECTIVE: To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis (RA) based on the transforming growth factor beta1 (TGF-ß1)/Smads signaling pathway. METHODS: One hundred rats were treated with saline [normal control (NC) group] or complete Freund's adjuvant (CFA) by right plantar injection for the RA model group, and the latter were randomly divided into 4 groups. Tripterygium wilfordii polyglycoside tablets (, TPT) have anti-inflammatory and are widely used in the clinical treatment of RA, therefore serving as a positive control group. Three days post injection rats were given TPT tablet (TPT group), acupuncture therapy (APT group), and moxibustion treatment (MOX group) for 15 consecutive days, while NC group and model group were equally grasped and fixed and received normal saline. Rat joint swelling scores and arthritis index (AI) were evaluated in each group before the CFA challenge, therapy and after receiving therapy. Myocardial ultrastructure was observed by electron microscope. Enzyme-linked immunosorbent assay was used to detect cardiac troponin I (cTnI) levels in rat myocardial tissue. Quantitative reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-ß signaling molecules including TGF-ß1, Smad2, Smad3, Smad4, and Smad7. Myocardial metabolomics was analyzed using gas chromatography-mass spectrometer. RESULTS: Compared with model group, RA model rats receiving TPT, acupuncture, or moxibustion therapy all showed reduced joint swelling scores and AI (all P < 0.01) and improved myocardial damage, whereas rats treated with moxibustion were found to be more marked. Consistently, the expressions of cTnI, TGF-ß1, Smad2, Smad3, and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT, APT and MOX group when compared with model group, while the levels of Smad7 showed the opposite result (all P < 0.01). Moreover, the dissection of metabolomics suggested a novel metabolite biomarker panel including D-Xylulose 5-phosphate, dihydroxyacetone phosphate, arachidonic acid, etc was defined and implicated in amino acid, glucose, and fatty acid metabolic processes as revealed by principal component analysis and partial least squares discriminant analysis. CONCLUSION: Moxibustion prevents RA-induced inflammatory response and offers potent therapeutic effects on myocardial dysfunctions. The protective effects might be associated with its role in TGF-ß1 inactivation and metabolic reprogramming.

Identification and functional study of detoxification-related genes in response to tolfenpyrad stress in Glyphodes pyloalis Walker (Lepidoptera: Pyralidae).

Glyphodes pyloalis Walker (G. pyloalis) is a common destructive mulberry pest. Due to the long-term and frequent use of insecticides, it has developed tolerance to commonly used insecticides. Tolfenpyrad (TFP) is a novel pyrazole heterocyclic insecticide. In order to understand the TFP detoxification mechanism of G. pyloalis larvae, we first estimated the LC30 dose of TFP for 3rd instar G. pyloalis larvae. Next, we identified genes that were differentially expressed in 3rd instar G. pyloalis larvae treated with TFP compared to the control group by transcriptome sequencing. In total, 86,949,569 and 67,442,028 clean reads were obtained from TFP-treated and control G. pyloalis larvae, respectively. A total of 5588 differentially expressed genes (DEGs) were identified in TFP-treated and control G. pyloalis larvae, of which 3084 genes were upregulated and 2504 genes were downregulated. We analyzed the expression of 43 candidate detoxification enzyme genes associated with insecticide tolerance using qPCR. According to the spatiotemporal expression pattern of DEGs, we found that CYP6ABE1, CYP333A36 and GST-epsilon8 were highly expressed in the midgut, while CarEs14 was strongly expressed in haemolymph. Furthermore, we successfully knocked down these genes by RNA interference. After silencing CYP6ABE1 and CYP333A36, bioassay showed that the mortality rate of TFP-treated G. pyloalis larvae was significantly higher compared to the control group. This study provides a theoretical foundation for understanding the sensitivity of G. pyloalis to TFP and establish the basis for the effective and green management of this pest.

A self-censoring model for multivariate nonignorable nonmonotone missing data.

We introduce an itemwise modeling approach called "self-censoring" for multivariate nonignorable nonmonotone missing data, where the missingness process of each outcome can be affected by its own value and associated with missingness indicators of other outcomes, while conditionally independent of the other outcomes. The self-censoring model complements previous graphical approaches for the analysis of multivariate nonignorable missing data. It is identified under a completeness condition stating that any variability in one outcome can be captured by variability in the other outcomes among complete cases. For estimation, we propose a suite of semiparametric estimators including doubly robust estimators that deliver valid inferences under partial misspecification of the full-data distribution. We also provide a novel and flexible global sensitivity analysis procedure anchored at the self-censoring. We evaluate the performance of the proposed methods with simulations and apply them to analyze a study about the effect of highly active antiretroviral therapy on preterm delivery of HIV-positive mothers.

Non-parametric inference about mean functionals of non-ignorable non-response data without identifying the joint distribution.

We consider identification and inference about mean functionals of observed covariates and an outcome variable subject to non-ignorable missingness. By leveraging a shadow variable, we establish a necessary and sufficient condition for identification of the mean functional even if the full data distribution is not identified. We further characterize a necessary condition for n-estimability of the mean functional. This condition naturally strengthens the identifying condition, and it requires the existence of a function as a solution to a representer equation that connects the shadow variable to the mean functional. Solutions to the representer equation may not be unique, which presents substantial challenges for non-parametric estimation, and standard theories for non-parametric sieve estimators are not applicable here. We construct a consistent estimator of the solution set and then adapt the theory of extremum estimators to find from the estimated set a consistent estimator of an appropriately chosen solution. The estimator is asymptotically normal, locally efficient and attains the semi-parametric efficiency bound under certain regularity conditions. We illustrate the proposed approach via simulations and a real data application on home pricing.

Predictive effect of the decline in CD4+ T cell levels in blood on infection in patients with severe hemorrhagic stroke and mechanism.

Objective: The purpose of this research was to evaluate the influence of immunity on infection in patients with severe hemorrhagic stroke and explore the mechanism underlying this connection. Methods: Clinical data obtained from 126 patients with severe hemorrhagic stroke were retrospectively analyzed, and the factors affecting infection were screened by multivariable logistic regression models. Nomograms, calibration curves, the Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis were used to examine the effectiveness of the models in evaluating infection. The mechanism underlying the reduction in CD4+ T-cell levels in blood was explored by analysis of lymphocyte subsets and cytokines in cerebrospinal fluid (CSF) and blood. Results: The results showed that CD4+ T-cell levels of <300/µL was an independent risk factor for early infection. The models for multivariable logistic regression involving the CD4+ T-cell levels and other influencing factors had good applicability and effectiveness in evaluating early infection. CD4+ T-cell levels decreased in blood but increased in CSF. Similarly, interleukin (IL)-6 and IL-8 levels in CSF had a significant increase, generating a substantial concentration gradient between the CSF and the blood. Conclusion: Reduced blood CD4+ T-cell counts among patients who had severe hemorrhagic stroke increased the risk of early infection. CSF IL-6 and IL-8 may be involved in inducing the migration of CD4+ T cells into the CSF and decreasing blood CD4+ T-cell levels.

ß-Arylation of Racemic Secondary Benzylic Alcohols to Access Enantioenriched ß-Arylated Alcohols.

The transformation of alcohols into value-added products is of great importance, as simple alcohols are widespread and can be easily derived from both fossil fuels and biomass. The selective functionalization of a sp3 C-H bond on the alkyl side chain of an alcohol over its hydroxyl group would offer an expedient route to expand the chemical space of alcohols but it remains a challenging task. Harnessing the borrowing hydrogen strategy, the ß-arylation of secondary alcohols with aryl bromides has been achieved in this study, which allows for the selective functionalization of a ß-Csp3 -H bond in an alcohol substrate. Under the catalysis of a Pd complex, secondary alcohols reacted with aryl bromides to afford 1,2-diaryl alcohols with broad substrate scope in the presence of a ketone additive. Furthermore, the enantioconvergent version of the reaction has also been realized, transforming racemic secondary alcohols into enantioenriched chiral 1,2-diaryl alcohols under the cooperative Pd and Ru catalysis. Mechanism studies indicate that the reactions are enabled by borrowing hydrogen catalysis.

Data Integration in Causal Inference.

Integrating data from multiple heterogeneous sources has become increasingly popular to achieve a large sample size and diverse study population. This paper reviews development in causal inference methods that combines multiple datasets collected by potentially different designs from potentially heterogeneous populations. We summarize recent advances on combining randomized clinical trial with external information from observational studies or historical controls, combining samples when no single sample has all relevant variables with application to two-sample Mendelian randomization, distributed data setting under privacy concerns for comparative effectiveness and safety research using real-world data, Bayesian causal inference, and causal discovery methods.

Improving efficiency of inference in clinical trials with external control data.

Suppose we are interested in the effect of a treatment in a clinical trial. The efficiency of inference may be limited due to small sample size. However, external control data are often available from historical studies. Motivated by an application to Helicobacter pylori infection, we show how to borrow strength from such data to improve efficiency of inference in the clinical trial. Under an exchangeability assumption about the potential outcome mean, we show that the semiparametric efficiency bound for estimating the average treatment effect can be reduced by incorporating both the clinical trial data and external controls. We then derive a doubly robust and locally efficient estimator. The improvement in efficiency is prominent especially when the external control data set has a large sample size and small variability. Our method allows for a relaxed overlap assumption, and we illustrate with the case where the clinical trial only contains a treated group. We also develop doubly robust and locally efficient approaches that extrapolate the causal effect in the clinical trial to the external population and the overall population. Our results also offer a meaningful implication for trial design and data collection. We evaluate the finite-sample performance of the proposed estimators via simulation. In the Helicobacter pylori infection application, our approach shows that the combination treatment has potential efficacy advantages over the triple therapy.

Double Negative Control Inference in Test-Negative Design Studies of Vaccine Effectiveness.

The test-negative design (TND) has become a standard approach to evaluate vaccine effectiveness against the risk of acquiring infectious diseases in real-world settings, such as Influenza, Rotavirus, Dengue fever, and more recently COVID-19. In a TND study, individuals who experience symptoms and seek care are recruited and tested for the infectious disease which defines cases and controls. Despite TND's potential to reduce unobserved differences in healthcare seeking behavior (HSB) between vaccinated and unvaccinated subjects, it remains subject to various potential biases. First, residual confounding bias may remain due to unobserved HSB, occupation as healthcare worker, or previous infection history. Second, because selection into the TND sample is a common consequence of infection and HSB, collider stratification bias may exist when conditioning the analysis on testing, which further induces confounding by latent HSB. In this paper, we present a novel approach to identify and estimate vaccine effectiveness in the target population by carefully leveraging a pair of negative control exposure and outcome variables to account for potential hidden bias in TND studies. We illustrate our proposed method with extensive simulation and an application to study COVID-19 vaccine effectiveness using data from the University of Michigan Health System.

Nile tilapia DNA sensor STING is involved in the IFN-ß and AP-1 signaling pathways in the immune response dependent on DDX41.

Stimulator of interferon genes (STING) plays important roles in innate immunology. In this study, we isolated the STING gene in Nile tilapia, termed OnSTING. Using quantitative RT-PCR, we explored the expression patterns of the OnSTING gene. Using dual-luciferase reporter assays, we revealed the effect of STING overexpression on nuclear factor κB (NF-κB), IFN and AP activation in HEK 293 cells. Using coimmunoprecipitation, the interaction of STING and TRIF was studied. The effect of OnSTING overexpression on the antibacterial activity in tilapia was investigated. The results showed that upon stimulation with Streptococcus agalactiae, the OnSTING transcript was upregulated in all the tested tissues. OnSTING mRNA levels were very stable from 2.5 to 8.5 dpf. Moreover, OnSTING, OnIFN and IRF3 expression was induced by LPS, Poly (I:C), S. agalactiae WC1535 and DCPS in Nile tilapia macrophages. Overexpression of OnSTING and OnDDX41 increased NF-κB activation in HEK293T cells and slightly increased IFN-ß activation but had no effect on AP-1 activation. OnSTING interacted with OnDDX41 and OnTBK1. However, OnSTING did not interact with TRIF. OnSTING overexpression in vivo decreased the sensitivity of tilapia to S. agalactiae infection. These results are helpful for clarifying the innate immune response against bacterial infection in Nile tilapia.

Impairment of superovulation on the establishment of pregnancy in mice / 解剖学报

Objective To explore whether superovulation impairs the process of pregnancy establishment in mice by changing the intrauterine environment. Methods The implantation and pregnancy of superovulated and normal mice were compared. The superovulated mice were subjected to unilateral tubal ligation on day 0. 5 and blastocysts were transplanted to the other uterine horn on day 2. 5. The number of implantation sites of bilateral uterine horn was compared. The differences between preimplantation uteri of superovulated and normal pseudopregnancy mice were compared by tissue sections and high-throughput sequencing. Bioinformatics analysis was performed on the differentially expressed genes in two groups. Results Compared with the control group, the pregnancy rate of mice in the superovulation group decreased significantly. The number of implantation sites in the superovulation group was higher than the control. There was no significant difference in the pregnancy rate of the uterine horn between the control side and the transplanted side of the superovulated mice. The endometrium was thinned and the number of glands was reduced in superovulated pseudopregnancy mice. The gene expression patterns of preimplantation uterus in superovulation pseudopregnancy and normal pseudopregnancy mice were different. There were 1097 significantly differentially expressed genes, including 752 up-regulated genes and 345 down-regulated genes. Bioinformatics analysis showed that differentially expressed genes are mainly involved in biological processes, such as decidualization, response to progesterone, positive regulation of angiogenesis. They were mainly enriched in FoxO signaling pathway, cell cycle pathway and steroid biosynthesis pathway. Conclusion Superovulation impaired the process of establishing pregnancy and altered the gene expression patterns of biomarker of uterine receptivity in mice.

Differential expression of LLGL2 in prostate ductal adenocarcinoma and acinar adenocarcinoma and its significance / 中华病理学杂志

Objective: To investigate the expression differences of LLGL2 between prostatic ductal adenocarcinoma (PDA) and prostatic acinar adenocarcinoma, and its potential clinical significance. Methods: Eighteen patients diagnosed of PDA or prostatic acinar adenocarcinoma with PDA component by histopathology during January 2015 and December 2019 in the Beijing Hospital, China were retrospectively studied. The transcriptome analysis was conducted using the tissue of PDA and prostatic acinar adenocarcinoma. Differentially expressed genes and the differences in expression profiles were identified. Further, differentially expressed proteins were verified by immunohistochemistry. Results: The tissue from 8 of the 18 patients were used for transcriptome analysis, the results of which were compared with data from public databases. 129 differentially expressed genes were identified. 45 of them were upregulated while 84 were downregulated. The results of gene enrichment analysis and gene oncology (GO) analysis revealed that the differentially expressed genes were mostly enriched in the hypertrophic cardiomyopathy and interleukin-17 related pathways. GPAT2, LLGL2, MAMDC4, PCSK9 and SMIM6 were differentially expressed between PDA and prostatic acinar adenocarcinoma. Moreover, LLGL2 was more likely expressed in the cytoplasm (P=0.04) than the nucleus (P<0.01) in PDA, compared with prostatic acinar adenocarcinoma. Conclusions: The gene expression profiling indicates that PDA are very similar to prostatic acinar adenocarcinoma. Among the differentially expressed proteins screened and verified in this study, the expression of GPAT2, LLGL2, MAMDC4 and PCSK9 is increased in PDA, while that of SMIM6 is reduced in PDA. The expression of LLGL2 shows significantly different patterns between PDA and prostatic acinar carcinoma, and thus may help differentiate PDA from prostatic acinar adenocarcinoma in clinical practice.

Analysis of 7 cases of delayed diagnosis of primary upper tract urothelial carcinoma with calculi / 现代泌尿外科杂志

【Objective】 To reduce the misdiagnosis rate by analyzing the clinical data of patients with primary upper tract urothelial carcinoma (UTUC) complicated with calculi. 【Methods】 Clinical data of 7 UTUC with calculi patients treated during Sep.2018 and Apr.2022 were retrospectively analyzed, including general data, time from visit to diagnosis, imaging data, urine exudation cytological results, surgical methods, pathological stages and follow-up data. 【Results】 The ratio of male to female was 3∶4, and the mean age was 66.4 (55-72) years. The initiate imaging examination results only showed calculi, but did not indicate suspicious tumor (including 1 case with missing data). The median time from the first visit to diagnosis was 12 months (5-36 months). Of all 7 cases, 2 (2/4) were clinically diagnosed by enhanced CT, 3 (3/4) by MRI, and 2 (2/7) by positive urine exudation cytology. All patients received surgical treatment. Postoperative pathology showed 85.71% (6/7) were high-grade UTUC. Postoperative staging was T1N0M0 in 4 cases, T3N0M0 in 2 cases, and T4N2M0 in 1 case. Adjuvant chemotherapy was conducted in 2 cases. During the median follow-up of 12 months (6-41), 1 case developed multiple systemic metastases in month 9, while the other cases had no recurrence or metastasis. 【Conclusion】 For UTUC patients without obvious filling defect on imaging, especially when ipsilateral calculi were complicated, misdiagnosis should be alerted for timely treatment and better prognosis.

Application of indocyanine green angiography in repair of facial soft tissue defect using superficial temporal artery based forehead flap / 中国修复重建外科杂志

OBJECTIVE@#To explore the feasibility of using indocyanine green angiography in mapping the superficial temporal vessels and assisting design and harvesting of the superficial temporal artery based forehead flap.@*METHODS@#A clinical data of 14 patients with facial soft tissue defects repaired with superficial temporal artery based forehead flaps between October 2015 and November 2022 was retrospectively analyzed. There were 9 males and 5 females with a median age of 9.5 years (range, 3-38 years). The forehead flaps were used to reconstruct facial soft tissue defects following excision of facial scar (8 cases) or congenital melanocyte nevus (6 cases). The size of defects ranged from 3 cm×2 cm to 24 cm×9 cm. Before operation, the indocyanine green angiography was used to map the superficial temporal artery and vein, and to analyze the relationship of the arteries and veins. The forehead flaps with unilateral superficial temporal fascia as the pedicle was transferred to repair the small facial defect in 2 cases. The facial pedicle contained the frontal branch of the superficial temporal artery and 2 cm of the superficial temporal fascia around the vessel, and the tiny accompanying vein of the frontal branch of the superficial temporal artery was used as the outflow of the flap. The forehead flaps with the skin pedicle including bilateral or unilateral superficial temporal fascia and the overlying skin was pre-expanded and transferred to repair the large facial defect in 12 cases. The skin pedicle contained the frontal branch of superficial temporal artery and one of main branches of superficial temporal vein. Among the 12 cases, the frontal branch of superficial temporal vein was used as the outflow in 4 cases, and the parietal branch was used as the outflow in 8 cases. The size of the flaps ranged from 3 cm×2 cm to 30 cm×13 cm. The skin pedicles were divided at 3 weeks after the flap transfer.@*RESULTS@#Indocyanine green angiography could clearly showed the course and branching of the superficial temporal artery and vein. Individual differences existed in the location where the frontal branch of the superficial temporal artery entered the forehead. The superficial temporal vein had great variability and did not follow the artery. One patient had expander-related complication, which resulted in 3-cm flap necrosis. The necrotic tissue was debrided and repaired with skin grafting. The other flaps totally survived and the incisions healed by first intention. All patients were followed up 2-24 months, with a median of 11.5 months. The color, texture, and thickness of the flaps matched well with those of recipient sites. Hypertrophic scar was not observed in recipient or donor site. All patients were satisfied with the reconstructive outcomes.@*CONCLUSION@#Indocyanine green angiography can clearly visualize the course and the branches of the superficial temporal arteries and veins, which can help surgeons understand the position, distribution, and concomitant relationship of the superficial temporal vessels, and make a rational surgical plan of the forehead flap.