Sjögren's syndrome with adult-onset Still's disease: an overlap syndrome?

Adult-onset Still's disease (AOSD) is a rare systemic auto-inflammatory disease that is an exclusive diagnosis that needs to previously exclude infections, tumors, and rheumatic diseases. There are few reports on AOSD overlapping with other rheumatic diseases. We reported a 55-year-old male who presented with a high, daily spiking fever associated with an evanescent salmon-pink rash, arthralgia, and sore throat. He had a history of dryness of the mouth and eyes for decades with no medical treatment. On admission, tests for antinuclear antibody (ANA) and anti-SSA/Ro-52 antibody were positive, and salivary gland biopsy showed focal lymphocytic sialadenitis with a focus score of ≥ 1 foci/4 mm2, which was consistent with a diagnosis of primary Sjögren's syndrome (SS). However, the disease activity of SS was low at the time of the report. Combined with significantly elevated acute phase reactants, the patient also met the classification criteria of both Yamakuchi and Futel for AOSD. His clinical symptoms were relieved quickly with glucocorticoid therapy. We also reviewed the literature on SS with AOSD and AOSD with other rheumatic diseases, and scattered case reports were retrieved. So we think that AOSD is not an absolutely exclusive diagnosis and can occur in patients with other rheumatic diseases. To our knowledge, this is the only literature review of a reported AOSD case in a SS patient.

Tissue eosinophils and mucous inflammatory cytokines for the evaluation of olfactory recovery after endoscopic sinus surgery in patients with nasal polyposis.

The etiologies of chronic rhinosinusitis with nasal polyps (CRSwNP)-associated olfactory dysfunction have several potentially overlapping hypotheses. Understanding the association of tissue eosinophils and mucous inflammatory cytokines with olfactory function and identifying predictors of olfactory outcomes in patients with nasal polyposis after surgery is fundamental for future clinical care and research. METHODS: Eighty-five patients who underwent endoscopic surgery for nasal polyposis were enrolled in this study. Olfactory measurements were performed before surgery and 3-6 months after surgery using a T&T olfactometer. Baseline characteristics of CRSwNP patients were collected, and Spearman's rho correlation was performed to assess the association of olfactory function with tissue eosinophils and mucous inflammatory cytokines. A multivariate logistic regression model was used to assess the independent predictors of olfactory outcomes after surgery. RESULTS: Here, 85 CRSwNP patients, including 25 patients without olfactory disorder and 60 patients with hypo-anosmia, were evaluated. Of the 60 patients with preoperative hypo-anosmia, 22 did not have improved olfactory function, and 38 demonstrated normal olfactory function after surgery based on the T&T olfactometer results. The levels of tissue eosinophil, interleukin-5 (IL-5), IL-13, eotaxin-3, and periostin in the preoperative hypo-anosmia group were higher than those in the preoperative normosmia group. Tissue eosinophil count, IL-5, and periostin levels in patients without olfactory improvement were higher than those in patients with olfactory improvement. The tissue eosinophil count, blood eosinophil count, and nasal mucus levels of IL-5, eotaxin-3, and periostin were significantly correlated with olfactory function in all patients with CRSwNP. The IL-5 level remained a strong predictor of poor olfactory outcomes after surgery. CONCLUSIONS: Both tissue eosinophils and mucous inflammatory cytokines, including IL-5, IL-13, eotaxin-3, and periostin, may contribute to the pathogenesis of CRSwNP-associated olfactory dysfunction. Higher IL-5 levels are associated with a lower chance of olfactory function recovery after each surgical revision.

A Risk Prediction Model of Readmission for Chinese Patients after Coronary Artery Bypass Grafting.

BACKGROUND: Predictive models can be used to assess the risk of readmission for patients after coronary artery bypass grafting (CABG). However, the majority of the existing prediction models have been developed based on data of western population. Our objective was to develop and validate a risk prediction model for Chinese patients after CABG. METHODS: This study was conducted among 1983 patients who underwent CABG in Wuhan Asian Heart Hospital from January 2017 to October 2019. Pearson's chi-squared and multivariate logistic regression were performed to investigate the risk factors of readmission after CABG. The area under the ROC curve and Hosmer-Lemeshow test were used to validate the discrimination and calibration of the model, respectively. RESULTS: Six risk factors were predictive of readmission: age≥65 years (odds ratio [OR] = 2.19; 95% confidence interval [CI]: 1.11-4.34; P = 0.024),  female (OR = 2.46; 95%CI: 1.26-4.80; P = 0.008), private insurance (OR = 4.23; 95%CI: 1.11-16.11; P = 0.034), diabetes (OR = 2.351; 95%CI: 1.20-4.59; P = 0.012), hypertension (OR = 2.33; 95%CI: 1.16-4.66; P = 0.017), and congenital heart disease (OR = 6.93;95%CI: 2.04-23.52; P = 0.002). The area under the curve c-statistic was 0.876 in the derivation sample and 0.865 in the validation sample. Hosmer-Lemeshow test: P=0.561. CONCLUSION: The risk prediction model in our study can be used to predict the risk of readmission in Chinese patients after CABG.

A New Inductive Debris Sensor Based on Dual-Excitation Coils and Dual-Sensing Coils for Online Debris Monitoring.

Lubricants are of key importance for mechanical processing, and exist in nearly every mechanical system. When the equipment is in operation, debris particles will be generated in mechanical lubricants. The detection of debris particles can indicate the wear degree of machinery components, and provide prognosis warning for the system before the fault occurs. In this work, a novel type of inductive debris sensor consisting of two excitation coils and two sensing coils is proposed for online debris monitoring. The developed sensor was proven to be of high sensitivity through experimental verification. The testing results show that, using the designed sensor, ferrous metal debris with a size of 115 µm and nonferrous metal debris with a size of 313 µm in a pipe with an inner diameter of 12.7 mm can be effectively detected. Moreover, the proposed inductive debris sensor structure has better sensitivity at higher throughput and its design provides a useful insight into the development of high-quality sensors with superior performances.

MicroRNA-33a-5p sponges to inhibit pancreatic ß-cell function in gestational diabetes mellitus LncRNA DANCR.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common medical complication associated with pregnancy, which may impose risks on both mother and fetus. Micro RNAs (miRNAs) and long noncoding RNAs (lncRNAs) are implied as vital regulators in GDM. A recent paper revealed dysregulation of miR-33a-5p in placental tissues of GDM patients. However, the biological function of miR-33a-5p in GDM remains elusive. This study focused on exploring the function and underlying mechanisms of miR-33a-5p in GDM. METHODS: 12 GDM pregnancies and 12 healthy pregnancies were enrolled in the study. INS-1 cell line was applied in in vitro experiments. The expression levels of miR-33a-5p, lnc-DANCR (Differentiation Antagonizing Non-Protein Coding RNA), and ABCA1 (ATP-binding cassette transporter 1) mRNA were determined by RT-qPCR assay. Glucose and insulin levels were measured by ELISA assay. Luciferase reporter assay and western blot assay were applied to validate the target of miR-33a-5p. RESULTS: miR-33a-5p was upregulated in the blood samples from GDM, and was positively correlated with blood glucose (p < 0.0001). Overexpression or inhibition of miR-33a-5p significantly inhibited or promoted cell growth and insulin production of INS-1 cells (p < 0.01). Furthermore, ABCA1 is a direct target of miR-33a-5p, and lnc-DANCR functions as a sponge for miR-33a-5p to antagonize the function of miR-33a-5p in INS-1 cells. CONCLUSION: Our study demonstrated that lnc-DANCR-miR-33a-5p-ABCA1 signaling cascade plays a crucial role in the regulation of the cellular function of INS-1 cells.

Application Value of Rapid Predictive Model for Readmission Risk in Patients after CABG.

OBJECTIVE: To explore the value of a rapid risk predictive model for the readmission of patients after CABG in China. METHODS: The rapid predictive model of readmission risk was translated into Chinese, and then validated with data from 758 patients who underwent CABG in Wuhan Asian Heart Hospital from January 2018 to June 2019. The discrimination was tested by area under the ROC curve (AUC), and the calibration was tested by Hosmer-Lemeshow test. RESULTS: The rapid risk predictive model for readmission showed good discrimination and calibration in Chinese CABG patients (The area under ROC curve c-statistic: 0.704, 95% CI: 0.614-0.794; Hosmer-Lemeshow test: P = .955). CONCLUSION: The rapid readmission risk predictive model can be used in Chinese CABG patients soon after admission.

Use of profession-role exchange in an interprofessional student team-based community health service-learning experience.

BACKGROUND: During interprofessional clinical practice, compared to understanding of one's own professional role and function, it might be more difficult to clarify the roles and contributions of the other health-care team members because of the inter-professional barrier. In order to provide students the opportunity for real experience with other professions in team environments and enhance their perceptions of other professions' roles, this study developed a comprehensive and multi-dimension extracurricular interprofessional education (IPE) model through designing and integrating a profession-role exchange component, that was medical students as pharmacists or nurses, pharmacy students as physicians or nurses, and nursing students as physicians or pharmacists in the interprofessional health-care student team, into the service learning experience in a real community setting. METHODS: In this pre/post-intervention study, the effect of integrated profession-role exchange experiences on the students' attitudes towards interprofessional collaboration and their role clarification was evaluated among 60 student volunteers (20 medical students, 20 pharmacy students and 20 nursing students). All involved students were divided into the profession-role exchange intervention group and the control group. Subjects in the control group did not participate the profession-role exchange experiences, the other IPE procedures were the same for both groups. Three survey instruments for attitudes toward interprofessional clinical collaboration were respectively used to measure the students' attitudes toward physician-pharmacist, physician-nurse and nurse-pharmacist collaborations. "Roles and responsibilities" subscale of Readiness for Interprofessional Learning Scale was used to evaluate the overall role clarification during IPE. RESULTS: Compared to the control IPE activity, the addition of profession-role exchange component resulted in the significant increase in students' positive attitudes towards interprofessional collaboration, and the enhancement of students' role awareness. CONCLUSIONS: The profession-role exchange might be more effective and better initiate students to the practice of interprofessional collaboration, and could be used as an effective IPE tool for improving the role awareness of health-care students.

In vivo measurement of the dynamics of norepinephrine in an olfactory bulb following ischemia-induced olfactory dysfunction and its responses to dexamethasone treatment.

Information on the dynamics of molecules following olfactory dysfunction remains essential for understanding the molecular events involved in the pathological process of olfactory dysfunction. This study for the first time demonstrates a method based on the combination of in vivo microdialysis with high performance liquid chromatography (HPLC) and electrochemical detection (ECD) for the measurement of the dynamics of norepinephrine (NE) in the olfactory bulbs of Sprague-Dawley rats following olfactory dysfunction induced by brain ischemia and its responses toward dexamethasone treatment. The method possesses a high spatial resolution and benefits from in vivo microdialysis and high selectivity and is thus capable of measuring NE in the olfactory bulb of rats. With this method, the basal level of NE in the olfactory bulb was evaluated to be ca. 235 ± 25 nM (n = 6). This level was found to increase by 260 ± 90% at a time point of 240 min after brain ischemia with bilateral ligation of both common carotid arteries. The increase was found to be suppressed upon the treatment of the animals with 0.2% dexamethasone in the olfactory bulb. These results suggest that NE is involved in the pathological process of ischemia-induced olfactory dysfunction and this information is useful to further understand the molecular events involved in olfactory dysfunction.

Label-free detection of fibrinogen based on the fibrinogen-enhanced peroxidase activity of a fibrinogen-hemin composite.

A simple, label-free colorimetric method for the determination of fibrinogen (Fib) in plasma is presented. In this work, it was observed that Fib interacted with hemin to form a hemin-Fib composite. Because Fib prevented hemin from the formation of m-oxo-dimers, the hemin-Fib composite possesses excellent peroxidase-like activity. Importantly, the peroxidase-like activity of Fib-hemin increased with the increase in the Fib. This allows us to utilize the H2O2-ABTS colorimetric system for the quantitative analysis of Fib. This optimized method provided a linear determination range of 2.0-100 pM with a correlation of 0.9975. The limit of detection for Fib was experimentally determined to be 0.7 pM based on a signal-to-noise ratio (S/N) of 3. This novel approach provides a rapid, sensitive, cost efficient and robust bioassay for detection of Fib in pathology and clinical applications.

Pharmacy and nursing students' attitudes toward nurse-pharmacist collaboration at a Chinese university.

BACKGROUND: The collaborative working relationship of nurses with pharmacists has increasingly captured considerable attention. This study measured pharmacy and nursing students' attitudes toward nurse-pharmacist collaboration at a university in China. METHODS: This cross-sectional study was conducted to assess the attitudes toward nurse-pharmacist collaboration using a self-developed scale delivered to a sample involving 202 nursing students and 258 pharmacy students enrolled in Wuhan University of Science and Technology. RESULTS: Completed instruments were returned by 192 nursing students (95.0% effective response rate) and 249 pharmacy students (96.5% effective response rate). The average students' score of attitudes toward nurse-pharmacist collaboration was 78.85 out of a total of 100. No significance was found for the attitudes toward nurse-pharmacist collaboration between two professions or between gender. The college freshmen (first-year) students had the maximum scores suggesting the most positive attitude toward nurse-pharmacist collaboration, followed by second- and third-year students, while final-year (fourth-year) students had the least. CONCLUSION: The students had somewhat positive attitudes toward nurse-pharmacist collaboration, but there is still room for improvement.

Online electrochemical system as an in vivo method to study dynamic changes of ascorbate in rat brain during 3-methylindole-induced olfactory dysfunction.

This study demonstrates the application of an online electrochemical system (OECS) as an in vivo method to investigate the dynamic change of microdialysate ascorbate in the olfactory bulb (OB) of rats during the acute period of olfactory dysfunction induced by intraperitoneal (i.p.) injection of 3-methylindole (3-MI). The OECS is developed by directly coupling an electrochemical detector to in vivo microdialysis for the direct monitoring of ascorbate. The system benefits from the good electrochemical activity of single-walled carbon nanotubes towards the oxidation of ascorbate and exhibits high selectivity, good stability, reproducibility and linearity for the measurement of ascorbate in the OB under physiological conditions. With this method, the basal level of microdialysate ascorbate in the OB is determined to be 48.64 ± 5.44 µM. The administration of 3-MI clearly increases the microdialysate ascorbate in the OB after 3-MI treatments and this increase is obviously alleviated by intravenous administration of ascorbate and glutathione (GSH) within 10 min after i.p. injection of 3-MI. These observations with the OECS suggest that ascorbate may be involved in chemical processes during the early stages of 3-MI-induced olfactory dysfunction. This study essentially validates the OECS as an in vivo method for effective measurement of ascorbate in the OB in rat brain and such a method will find interesting applications in investigating chemical process associated with ascorbate underlying olfactory dysfunction.

Molecular epidemiology of the enteroviruses associated with hand, foot and mouth disease/herpangina in Dongguan, China, 2015.

Enteroviruses (EVs) are the etiological agents involved in most cases of hand, foot and mouth disease (HFMD) and herpangina (HA). Information on the epidemiology profiles of EVs in China is very limited, as the present surveillance system of China focuses on CAV16 and EV71, and no published data are available in Dongguan. The aim of this study is to determine the prevalence of EVs among patients with HFMD and HA in Dongguan, China, during 2015. A total of 271 clinical stool specimens that were clinically determined to be positive for enteroviruses were genotyped by semi-nested polymerase chain reaction (PCR) for the VP1 genes of EVs. The results showed that a total of 14 enterovirus genotypes were identified among HFMD and HA patients in this study. CVA6 was the most common genotype for HFMD, and CVA2 accounted for the majority of HA cases in this study. Sequence and phylogenetic analysis showed that all of the CVA6 and CVA2 strains identified in our study displayed a close genetic relationship to strains identified in other cities in China. This study also demonstrates that there are associations between particular causative enterovirus genotypes and some clinical symptoms, which may provide useful information for improving case prevention, diagnosis and treatment of HFMD and HA.

Brief Report: Databases in the Asia-Pacific Region: The Potential for a Distributed Network Approach.

BACKGROUND: This study describes the availability and characteristics of databases in Asian-Pacific countries and assesses the feasibility of a distributed network approach in the region. METHODS: A web-based survey was conducted among investigators using healthcare databases in the Asia-Pacific countries. Potential survey participants were identified through the Asian Pharmacoepidemiology Network. RESULTS: Investigators from a total of 11 databases participated in the survey. Database sources included four nationwide claims databases from Japan, South Korea, and Taiwan; two nationwide electronic health records from Hong Kong and Singapore; a regional electronic health record from western China; two electronic health records from Thailand; and cancer and stroke registries from Taiwan. CONCLUSIONS: We identified 11 databases with capabilities for distributed network approaches. Many country-specific coding systems and terminologies have been already converted to international coding systems. The harmonization of health expenditure data is a major obstacle for future investigations attempting to evaluate issues related to medical costs.

Correlation of Eosinophils and Type 2 Inflammatory Mediators with Osteitis in Chronic Rhinosinusitis with Nasal Polyps.

Objective: Osteitis is more prevalent in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), making the disease refractory and prone to recurrence. However, the pathophysiologic mechanism of osteitis formation in CRS has not been fully elucidated, and this study aimed to further elucidate the association of eosinophils and type 2 inflammatory mediators with osteitis in patients with CRSwNP. Methods: This retrospective study collected clinical data on 125 cases of CRSwNP. The participants were categorized into two groups based on the presence or absence of osteitis in their sinus CT scan. The groups were classified as the osteitis group and the non-osteitis group. The clinical baseline data, type 2 inflammatory mediators, and eosinophils were compared between the two groups. The correlation between these factors and the Global Osteitis score scale (GOSS) was also evaluated. Results: There were 69 cases in the osteitis group and 56 cases in the non-osteitis group of CRSwNP patients. The prevalence of concomitant asthma (P=0.009), SNOT-22 score, LUND-MAKAY score, and LUND-KEDENY score were significantly higher in the osteitis group than in the non-osteitis group (All P values were < 0.001); the absolute values of IL-13 (P<0.001), periosteal proteins (P<0.001), and tissue eosinophils (P < 0.05) were significantly higher in the osteitis group as compared with the non-osteitis group. Logistic regression analysis showed that IL-13 and periosteal proteins were risk factors for CRSwNP osteitis (P<0.001). ROC curve analysis revealed that IL-13 had the highest predictive value (AUC=0.786) with a cut-off value of 5.8059 pg/mL, the sensitivity of 58.0%, and a specificity of 89.3% respectively. Conclusion: Osteitis could indicate the more severe symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), and elevated IL-13, periosteal proteins, and tissue eosinophils are risk factors for osteitis formation in patients with CRSwNP.

Prediction of Vasoactive-Inotropic Score on Prolonged Mechanical Ventilation in Adult Congenital Heart Disease Patients After Surgical Treatment Combined with Coronary Artery Bypass Grafting.

INTRODUCTION: This study aimed to investigate the predictive value of the vasoactive-inotropic score (VIS) at different time points for postoperative prolonged mechanical ventilation (PMV) in adult congenital heart disease patients undergoing surgical treatment combined with coronary artery bypass grafting. METHODS: Patients were divided into two groups that developed PMV or not. The propensity score matching method was applied to reduce the effects of confounding factors between the two groups. VIS at different time points (VIS at the end of surgery, VIS6h, VIS12h, and VIS12h max) after surgery were recorded and calculated. The value of VIS in predicting PMV was analyzed by the receiver operating characteristic (ROC) curve, and multivariate logistic regression was used to analyze independent risk factors. RESULTS: Among 250 patients, 52 were in the PMV group, and 198 were in the non-PMV group. PMV rate was 20.8%. After propensity score matching, 94 patients were matched in pairs. At each time point, the area under the ROC curve predicted by VIS for PMV was > 0.500, among which VIS at the end of surgery was the largest (0.805). The optimal cutoff point for VIS of 6.5 could predict PMV with 78.7% sensitivity and 72.3% specificity. VIS at the end of surgery was an independent risk factor for PMV (odds ratio=1.301, 95% confidence interval 1.091~1.551, P<0.01). CONCLUSION: VIS at the end of surgery is an independent predictor for PMV in patients with adult congenital heart disease surgical treatment combined with coronary artery bypass grafting.

Progress in the treatment of diabetic cardiomyopathy, a systematic review.

Diabetic cardiomyopathy (DCM) is a condition characterized by myocardial dysfunction that occurs in individuals with diabetes, in the absence of coronary artery disease, valve disease, and other conventional cardiovascular risk factors such as hypertension and dyslipidemia. It is considered a significant and consequential complication of diabetes in the field of cardiovascular medicine. The primary pathological manifestations include myocardial hypertrophy, myocardial fibrosis, and impaired ventricular function, which can lead to widespread myocardial necrosis. Ultimately, this can progress to the development of heart failure, arrhythmias, and cardiogenic shock, with severe cases even resulting in sudden cardiac death. Despite several decades of both fundamental and clinical research conducted globally, there are currently no specific targeted therapies available for DCM in clinical practice, and the incidence and mortality rates of heart failure remain persistently high. Thus, this article provides an overview of the current treatment modalities and novel techniques pertaining to DCM, aiming to offer valuable insights and support to researchers dedicated to investigating this complex condition.

Using phonocardiography to investigate maternal cardiac reserve function in gestational hypertension and pre-eclampsia.

AIM: This study used phonocardiography to investigate maternal cardiac reserve function in gestational hypertension and pre-eclampsia. METHOD: Ninety-nine pregnant women with gestational hypertension (50 cases) and pre-eclampsia (49 cases) were included in the study; 99 normotensive pregnant women acted as controls. Using phonocardiography, cardiac reserve function parameters for all participants were recorded: heart rate, the ratio of the first heart sound magnitude to the second heart sound magnitude (S1/S2) and the ratio of the diastolic duration to the systolic duration (D/S). RESULTS: The average values for S1/S2 in the pre-eclampsia and gestational hypertension groups were 4.3±2.2 and 2.2±1.1 respectively. The average D/S of the pre-eclampsia and gestational hypertension groups were 1.1±0.3 and 1.4±0.3 respectively. Cases of postnatal adverse maternal outcomes were only observed in the pre-eclampsia group. A small proportion (2 out of 28) suffered cardiac-related complications, with one of these two patients dying from cardiac failure. Both these cases had notably poor cardiac reserve function (S1/S2>5.00 and D/S<1) before delivery. The index S1/S2 increases and the index D/S decreases with increasing severity of hypertension-complicated pregnancies. CONCLUSIONS: Our findings indicate that cardiac reserve function declines with the increasing severity of hypertension during pregnancy. Phonocardiography is a useful, convenient and clinically worthwhile technique to monitor cardiac reserve function parameters of pregnant women with pre-eclampsia.

Ecological of human health risk of total petroleum hydrocarbons and four metals in seawater of the southeastern Bohai Sea, China.

To obtain systematic knowledge on the waterborne pollution status and ecological and human health risk of total petroleum hydrocarbons (TPHs) and metals in the southeastern Bohai Sea, seawater samples were collected in three seasons from 2014 to 2018. TPHs and mercury (Hg) levels were determined by ultraviolet spectrophotometry and cold atomic absorption spectrometry, respectively, and concentrations of copper (Cu), lead (Pb), and cadmium (Cd) were detected by anodic stripping voltammetry. Spatial distribution patterns indicated that these waterborne pollutants are mainly sourced from terrestrial inputs. Temporal variation showed that Pb contents decreased in the past five years, and summer exhibited higher concentrations of Hg, Cu, and Cd than spring and autumn. Spearman's rank correlation coefficients demonstrated that temperature correlated positively with Cu content, while dissolved oxygen, pH, and suspended particulate material correlated negatively with pollutant concentrations. While hazard quotient values were lower than 1 for TPHs, Hg, Pb, and Cd, the hazard quotient of Cu (4.88) was greater than 1, suggesting potential ecological risks of this element in seawater of the southeastern Bohai Sea. The total target hazard quotients of Hg, Cu, Pb, and Cd in seawater of the southeastern Bohai Sea were all lower than 1, which indicated that there was no noncarcinogenic risk caused by heavy metals in seawater of the southeastern Bohai Sea. However, the carcinogenic risk of Cd (1.54 × 10-5) was in the range of 10-6-10-4, which may lead to the occurrence of cancer. This study sounds an alarm for stricter control of metal emissions into this sea area.

Case report: ADULT syndrome: a rare case of congenital lacrimal duct abnormality.

Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare autosomal dominant inherited disease caused due to mutations in the TP63 gene. More commonly, mutations in the TP63 gene result in ectodermal dysplasia and/or orofacial cleft. ADULT syndrome is a type of ectoderm-related tissue dysplasia. This case report describes a patient with chronic tearing, congenital atresia, and obstruction of the lacrimal ducts, which are the main clinical manifestations of ADULT syndrome. This patient also presented with some clinical manifestations that were different from those of ADULT syndrome, namely, mild eyelid fusion and abnormal development of the fifth finger (a stiff fifth finger with camptodactyly that was shortened in length). The gene mutation in this patient was also at a site different from those usually reported in the literature. In this patient, c.518G > T resulted in p. G173V (accession number: NM_003722; exon4). We performed successful dacryocystorhinostomy and artificial lacrimal duct implantation. As shown above, we discussed the clinical characteristics and genetics of the disease in detail. In sharing this case, we aim to contribute to the current understanding of the genes and clinical manifestations of ADULT syndrome and to assist clinicians in the clinical diagnosis of TP63 mutation-related diseases.

Investigating subtypes of lung adenocarcinoma by oxidative stress and immunotherapy related genes.

Lung adenocarcinoma (LUAD) is one of the most widespread and fatal types of lung cancer. Oxidative stress, resulting from an imbalance in the production and accumulation of reactive oxygen species (ROS), is considered a promising therapeutic target for cancer treatment. Currently, immune checkpoint blockade (ICB) therapy is being explored as a potentially effective treatment for early-stage LUAD. In this research, we aim to identify distinct subtypes of LUAD patients by investigating genes associated with oxidative stress and immunotherapy. Additionally, we aim to propose subtype-specific therapeutic strategies. We conducted a thorough search of the Gene Expression Omnibus (GEO) datasets. From this search, we pinpointed datasets that contained both expression data and survival information. We selected genes associated with oxidative stress and immunotherapy using keyword searches on GeneCards. We then combined expression data of LUAD samples from both The Cancer Genome Atlas (TCGA) and 11 GEO datasets, forming a unified dataset. This dataset was subsequently divided into two subsets, Dataset_Training and Dataset_Testing, using a random bifurcation method, with each subset containing 50% of the data. We applied consensus clustering (CC) analysis to identify distinct LUAD subtypes within the Dataset_Training. Molecular variances associated with oxidative stress levels, the tumor microenvironment (TME), and immune checkpoint genes (ICGs) were then investigated among these subtypes. Employing feature selection combined with machine learning techniques, we constructed models that achieved the highest accuracy levels. We validated the identified subtypes and models from Dataset_Training using Dataset_Testing. A hub gene with the highest importance values in the machine learning model was identified. We then utilized virtual screening to discover potential compounds targeting this hub gene. In the unified dataset, we integrated 2,154 LUAD samples from TCGA-LUAD and 11 GEO datasets. We specifically selected 1,311 genes associated with immune and oxidative stress processes. The expression data of these genes were then employed for subtype identification through CC analysis. Within Dataset_Training, two distinct subtypes emerged, each marked by different levels of immune and oxidative stress pathway values. Consequently, we named these as the OX+ and IM+ subtypes. Notably, the OX+ subtype showed increased oxidative stress levels, correlating with a worse prognosis than the IM+ subtype. Conversely, the IM+ subtype demonstrated enhanced levels of immune pathways, immune cells, and ICGs compared to the OX+ subtype. We reconfirmed these findings in Dataset_Testing. Through gene selection, we identified an optimal combination of 12 genes for predicting LUAD subtypes: ACP1, AURKA, BIRC5, CYC1, GSTP1, HSPD1, HSPE1, MDH2, MRPL13, NDUFS1, SNRPD1, and SORD. Out of the four machine learning models we tested, the support vector machine (SVM) stood out, achieving the highest area under the curve (AUC) of 0.86 and an accuracy of 0.78 on Dataset_Testing. We focused on HSPE1, which was designated as the hub gene due to its paramount importance in the SVM model, and computed the docking structures for four compounds: ZINC3978005 (Dihydroergotamine), ZINC52955754 (Ergotamine), ZINC150588351 (Elbasvir), and ZINC242548690 (Digoxin). Our study identified two subtypes of LUAD patients based on oxidative stress and immunotherapy-related genes. Our findings provided subtype-specific therapeutic strategies.