AIM: To investigate the characteristics of anterior segment structure in first-degree relatives of patients with primary angle-closure glaucoma(PACG).METHODS: A total of 48 first-degree relatives of PACG patients aged 40-60 who were treated in the Affiliated Eye Hospital of Nanchang University from September 2020 to October 2022 were selected as the observation group. Additionally, 40 cases(40 eyes)of healthy individuals without glaucoma and family history of glaucoma at the same age group were collected as the control group. They were divided into younger group(40-49 years old)and elder group(50-60 years old). All subjects were examined with ultrasound biomicroscopy(UBM)and were measured using camera measure software. The parameters mainly included anterior chamber depth(ACD), anterior chamber area(ACA), anterior chamber width(ACW), anterior segment depth(ASD), angle open distance(AOD500), trabecular iris angle(TIA), trabecular iris area(TISA500), lens vault(LV), iris curve(IC), iris thickness(IT500), scleral ciliary process angle(SCPA), and iris ciliary process distance(ICPD).RESULTS: ACD, ACA, AOD500, TISA500 and TIA in the observation group were lower than those of the control group, and LV and IC were higher than those of the control group(all P<0.05). ACD, ACA, AOD500, TISA500, and TIA of the elder group were lower than those in the age-matched control group, while LV and IC were larger than those of the age-matched control group(all P<0.05). ACD, AOD500, TISA500, and TIA of the younger observation group were smaller than those of the age-matched control group, but LV and IC were significantly larger than those of the age-matched control group(all P<0.05). ACD, ACA, AOD500, TISA500 and TIA of the elder observation group were significantly lower than those of the younger observation group, and LV and IC were significantly larger than those of the younger observation group(all P<0.05). There was a difference in the distribution of ACD between the observation group and the control group(P<0.05), and the proportion of moderate to severe shallow anterior chambers was 10 times that of the control group. Correlation analysis showed that TISA500 was positively correlated with ACD and ACA, and negatively correlated with LV and IC, and TISA500 was mainly influenced by LV. IC had a positive correlation with LV and a negative correlation with ACD and ACA.CONCLUSION: First-degree relatives of PACG with normal axial length have a high risk of angle closure. The anterior segment structures of first-degree relatives of PACG are more crowded than normal individuals, and the lens forward shift may be the initial influencing factor for narrow angle.

Objective:To analyze the intraoperative hemodynamic management by hypotension prediction index(HPI)in one patient underwent robot-assisted laparoscopic cystectomy,and to provide the reference for anesthesia monitoring and hemodynamic management in the similar major surgery.Methods:The clinical data,intraoperative hemodynamic data,usage and dosage of vasoactive drugs,and clinical outcomes of one patient underwent robot-assisted laparoscopic cystectomy with HPI-guided intraoperative hemodynamic management were retrospectively analyzed,and the relevant literatures were reviewed.Results:The patient,a 72-year-old female,was admitted due to macroscopic hematuria for 5 months accompanied by dysuria for 3 months.The cystoscope results showed a 7 cm× 7 cm× 5 cm mass on the right side of the bladder trigone and a 4 cm × 3 cm × 3 cm mass near the bladder neck.The positron emission tomography/computed tomography(PET/CT)results showed thickening of the right posterior bladder wall with high metabolism,and the preliminary diagnosis was bladder malignancy.After preoperative anesthesia evaluation,the robot-assisted laparoscopic cystectomy was planned.After entering the operating room,the routine monitoring was conducted,and the monitor equipped with HPI software was used to guide intraoperative hemodynamic management.After routine anesthesia induction,the tracheal intubation was performed by video laryngoscope.The patient experienced intraoperative hypotension(IOH)for six times,the cumulative time of mean arterial pressure(MAP)＜65 mmHg was 13.7 min,accounting for 4.40％of the anesthesia duration,and the time-weighted average of MAP＜65 mmHg was 0.28 mmHg.The time range with HPI≥85 roughly overlapped with and included the period of MAP＜65 mmHg.At 146 time points with HPI≥85,the MAP remained greater than 65 mmHg at 68.5％(100/146)of the points.At 47 time points with MAP＜65 mmHg,HPI≥85 occurred at 97.9％(46/47)of the points.On the first postoperative day,the patient's hypersensitive cardiac troponin I was＜0.01 μg·L-1,and no perioperative adverse events occurred.The patient was discharged on the eighth day.Conclusion:HPI can promptly and accurately predict the occurrence of IOH in the patients undergoing robot-assisted laparoscopic cystectomy.The use of HPI-based hypotension correction strategies during surgery can maintain the time-weighted average of MAP＜65 mmHg at a lower level.

Objective:To explore the effects of body mass index (BMI) on the incidence of nocturnal hypertension in patients with hypertension.Methods:Totally 341 hospitalized hypertensive patients treated at the Affiliated Hospital of Jining Medical University from February to May 2023 were selected by convenience sampling. Patients' general information, clinical data, and 24-hour ambulatory blood pressure results were collected. A binomial Logistic regression analysis was conducted to investigate the factors affecting the occurrence of nocturnal hypertension in these patients. The relationship between BMI and the incidence of nocturnal hypertension was examined using threshold effect tests and smooth curve fitting.Results:The binomial Logistic regression analysis indicated that blood phosphate level was a factor influencing the occurrence of nocturnal hypertension in hypertensive patients ( P<0.05). Smooth curve fitting and threshold effect test results showed that the relationship between BMI and the incidence of nocturnal hypertension was curve-correlated, with a turning point at 24.61 kg/m 2. To the left of the turning point, there was no correlation ( P=0.130) ; to the right, there was a correlation ( P=0.016) . Conclusions:When the BMI of hypertensive patients exceeds 24.61 kg/m 2, the likelihood of nocturnal hypertension increases with rising BMI, providing a precise intervention target for weight management-based patient care in hypertension.

Objective:To explore the incidence of secondary hemophagocytic lymphohistiocytosis (sHLH) in elderly patients with severe SARS-CoV-2 infection, and to analyze and summarize its clinical features and risk factors for early identification of high-risk groups.Methods:A retrospective cohort study was conducted. From January to May 2020, No. 960 Hospital of People's Liberation Army, the Second Hospital Affiliated to Cheeloo College of Medicine of Shandong Province, the First Rehabilitation Hospital of Shandong Province, the Public Health Clinical Center Affiliated to Shandong University, and Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine received 248 patients over 60 years old who were diagnosed with severe SARS-CoV-2 infection during their assistance to Hubei or support for diagnosis and treatment of SARS-CoV-2 infection in Shandong Province. The clinical data of patients were collected. According to the hemophagocytic lymphohistiocytosis diagnosis scoring (HScore) criteria, the patients were divided into sHLH group (HScore > 169) and non-sHLH group (HScore < 98). The demographic data, clinical features, laboratory results, the proportion of organ failure and 60-day mortality of patients were collected and compared between the two groups. The risk factors of sHLH and 60-day death were evaluated through binary multivariate Logistic regression analysis in elderly patients with severe SARS-CoV-2 infection. The receiver operator characteristic curve (ROC curve) was plotted to analyze the diagnostic value of indicators only or combined for sHLH.Results:Among 248 elderly patients with severe SARS-CoV-2 infection, 82 patients with incomplete data and untraceable clinical outcomes, and 35 patients with HScore of 98-169 were excluded. Finally, 131 patients were enrolled in the final follow-up and statistics, including 25 patients in the sHLH group and 106 patients in the non-sHLH group. Compared with the non-sHLH group, plasma albumin (ALB), hemoglobin (Hb), lymphocyte count (LYM), platelet count (PLT), fibrinogen (Fib) and prealbumin (PAB) in the sHLH group were significantly reduced, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), MB isoenzyme of creatine kinase (CK-MB), serum creatinine (SCr), C-reactive protein (CRP), D-dimer, ferritin (Fer), lactate dehydrogenase (LDH), procalcitonin (PCT), cardiac troponin I (cTnI), triglycerides (TG), interleukin-6 (IL-6), total bilirubin (TBil) were significantly higher. The fever and fatigue in the sHLH group were more severe than those in the non-sHLH group, and the patients in the sHLH group had higher rates of shock, acute kidney injury, liver dysfunction, and cardiac injury than the non-sHLH group. The 60-day mortality of patient in the sHLH group was significantly higher than that in the non-sHLH group [84.0% (21/25) vs. 40.6% (43/106), P < 0.01]. Binary multivariate Logistic regression analysis showed that high Fer [odds ratio ( OR) = 0.997, 95% confidence interval (95% CI) was 0.996-0.998], D-dimer ( OR = 0.960, 95% CI was 0.944-0.977), LDH ( OR = 0.998, 95% CI was 0.997-0.999) and TG ( OR = 0.706, 95% CI was 0.579-0.860) were independent risk factors for sHLH in elderly patients with severe SARS-CoV-2 infection (all P < 0.01), while elevated Fer ( OR = 1.001, 95% CI was 1.001-1.002), LDH ( OR = 1.004, 95% CI was 1.002-1.005) and D-dimer ( OR = 1.036, 95% CI was 1.018-1.055) were independent risk factors for 60-day death of patients (all P < 0.01). The death risk of the sHLH patients was 7.692 times higher than that of the non-sHLH patients ( OR = 7.692, 95% CI was 2.466-23.987, P = 0.000). ROC curve analysis showed that a three-composite-index composed of LDH, D-dimer and TG had good diagnostic value for sHLH in elderly patients with severe SARS-CoV-2 infection [area under the ROC curve (AUC) = 0.920, 95% CI was 0.866-0.973, P = 0.000]. Conclusions:Elderly patients with severe SARS-CoV-2 infection complicated by sHLH tend to be critically ill and have refractory status and worse prognosis. High Fer, LDH, D-dimer and TG are independent risk factors for sHLH, and are highly suggestive of poor outcome. The comprehensive index composed of LDH, D-dimer and TG has good diagnostic value, and can be used as an early screening tool for sHLH in elderly patients with severe SARS-CoV-2 infection.

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M₄) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M₄ positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M₄ PET ligand that allows the non-invasive visualization of M₄ in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [¹⁸F] 12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [¹⁸F] 12 for the M₄-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [¹⁸F] 12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [¹⁸F] 12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [¹⁸F] 12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M₄ PET radioligand with promising attributes. The availability of a clinically validated M₄ PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

PiggyBac is a transposable DNA element originally discovered in the cabbage looper moth (Trichoplusia ni). The T. ni piggyBac transposon can introduce exogenous fragments into a genome, constructing a transgenic organism. Nevertheless, the comprehensive analysis of endogenous piggyBac-like elements (PLEs) is important before using piggyBac, because they may influence the genetic stability of transgenic lines. Herein, we conducted a genome-wide analysis of PLEs in the brown planthopper (BPH) Nilaparvata lugens (Stål) (Hemiptera: Delphacidae), and identified a total of 28 PLE sequences. All N. lugens piggyBac-like elements (NlPLEs) were present as multiple copies in the genome of BPH. Among the identified NlPLEs, NlPLE25 had the highest copy number and it was distributed on five chromosomes. The full length of NlPLE25 consisted of terminal inverted repeats and sub-terminal inverted repeats at both terminals, as well as a single open reading frame transposase encoding 546 amino acids. Furthermore, NlPLE25 transposase caused precise excision and transposition in cultured insect cells and also restored the original TTAA target sequence after excision. A cross-recognition between the NlPLE25 transposon and the piggyBac transposon was also revealed in this study. These findings provide useful information for the construction of transgenic insect lines.
Amino Acid Sequence ; Animals ; Animals, Genetically Modified ; DNA Transposable Elements/genetics* ; Hemiptera/genetics* ; Transposases/genetics*

Cardiomyopathy, Dilated/metabolism* ; Humans ; Microfilament Proteins/metabolism* ; Models, Cardiovascular ; Mutation ; Myocytes, Cardiac ; Pluripotent Stem Cells/metabolism* ; Transcription Factors/metabolism* ; Troponin T/metabolism*

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M
Antiviral Agents/therapeutic use* ; Binding Sites ; COVID-19/virology* ; Coronavirus Papain-Like Proteases/metabolism* ; Crystallography, X-Ray ; Drug Evaluation, Preclinical ; Drug Repositioning ; High-Throughput Screening Assays/methods* ; Humans ; Imidazoles/therapeutic use* ; Inhibitory Concentration 50 ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Naphthoquinones/therapeutic use* ; Protease Inhibitors/therapeutic use* ; Protein Structure, Tertiary ; Recombinant Proteins/isolation & purification* ; SARS-CoV-2/isolation & purification*

Objective:Analyze the hemagglutinin(HA) gene of influenza A strains in Liaoning Province from 2018 to 2019, calculate and evaluate the matching degree of influenza A strains and vaccine strains.Methods:49 influenza A strains from 2018 to 2019 were selected for sequencing, and the HA gene was analyzed for evolution; the mutation of antigen epitopes, glycosylation sites and receptor binding sites were studied; the matching degree between the epidemic strain and the vaccine was analyzed by pepidope model.Results:The 2018-2019 influenza pandemic season was concentrated in November-March, and the main pandemic strain was H1N1 pdm virus. Through evolutionary analysis, H1N1 pdm virus belonged to the 6B.1 branch, and the seasonal H3N2 strain was distributed in the 3C.2a branch, all of which belonged to the same branch as the vaccine strain this year. Some strains mutated at epitope and receptor binding sites. In some strains, glycosylation sites increased or were absent compared with vaccine strains, and no new glycosylation sites were present. The Pepitope model was used to evaluate the vaccine effect. H1N1 pdm virus vaccine of this year showed good protective effect, but the seasonal H3N2 vaccine strain showed negative protective effect for epidemic strain, which could not play an effective protective role. Conclusions:In 2018-2019, H1N1 epidemic strain in Liaoning Province had some variation, and the matching degree between H3N2 subtype epidemic strain and 2018-2019 vaccine strain was low. We should pay close attention to the gene variation of the epidemic strains and update the vaccine strains in time.

To Track the source of the infection through an investigation of a clustering of coronavirus disease 2019(COVID-19), and provide scientific basis and Strategy for the effective control of the aggregated epidemic situation of COVID-19. Field epidemiological method was used to survey the cases and related close contacts in a family clustering epidemic of COVID-19 in Dandong city of Liaoning Province. We obtained survey data for a descriptive analysis.Real time RT-PCR technique was used to detect 2019-nCoV nucleic acid in samples collected from cases and related close contacts combined with serum specific antibody detection. A total of 3 confirmed cases and 2 asymptomatic infection cases were discovered in the clustering epidemic, with 34 close contacts.Of eight close family contacts visiting from other province, one patient was on the same flight as the confirmed case, and her antibody IgG was positive. The family clustering was caused by past infection case who visited her friend through Wuhan from other provinces to local area.