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Jing-Hui Hu,1,2,* Hai-Jing Shi,1,2,* Zhen-Yu Han,3,* Hong Liu,4 Fu-Hai Ji,1,2 Ke Peng1,2 1Departments of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 4Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, USA*These authors contributed equally to this workCorrespondence: Ke Peng, Department of Anesthesiology, First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-159-6215-5989, Email pengke0422@163.comPurpose: Chronic postsurgical pain (CPSP) is a common complication after thoracic surgery and associated with long-term adverse outcomes. This study aims to develop two prediction models for CPSP after video-assisted thoracic surgery (VATS).Methods and Analysis: This single-center prospective cohort study will include a total of 500 adult patients undergoing VATS lung resection (n = 350 for development and n = 150 for external validation). Patients will be enrolled continuously at The First Affiliated Hospital of Soochow University in Suzhou, China. The cohort for external validation will be recruited in another time period. The outcome is CPSP, which is defined as pain with the numerical rating scale score of 1 or higher 3 months after VATS. Univariate and multivariable logistic regression analyses will be performed to develop two CPSP prediction models based on patients’ data of postoperative day 1 and day 14, respectively. For internal validation, we will use the bootstrapping validation technique. For external validation, the discrimination capability of the models will be assessed using the area under the receiver operating characteristic curve, and the calibration will be evaluated using the calibration curve and Hosmer–Lemeshow goodness-of-fit statistic. The results will be presented in model formulas and nomograms.Conclusion: Based on the development and validation of the prediction models, our results contribute to early prediction and treatment of CPSP after VATS.Trial Registration: Chinese Clinical Trial Register (ChiCTR2200066122).Keywords: chronic postsurgical pain, prediction, video-assisted thoracoscopic surgery

Hye Jin Shi, Jae Hee Wee, Joong Sik Eom Division of Infectious Diseases, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, KoreaCorrespondence: Joong Sik EomDivision of Infectious Diseases, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, (21565) 774 Beon-gil 21, Namdongdae-ro, Namdong-gu, Incheon, KoreaTel +82-32-460-2630Fax +82-32-460-2631Email helppl@gachon.ac.krBackground: Urinary tract infections (UTIs) caused by extended spectrum beta-lactamase (ESBL) producing pathogens have increased and are treated with carbapenem in general. Carbapenem use is associated with prolonged hospitalization or daily outpatient visit. The aim of this study was to investigate patients with UTIs by ESBL-producing pathogens for early discharge using an old oral antibiotic, trimethoprim-sulfamethoxazole (TMP-SMX), which is susceptible to ESBL-producing pathogens.Methods: Data on UTIs caused by ESBL-producing pathogens from a single tertiary hospital were collected retrospectively. Patients who had been treated with intravenous carbapenems or oral TMP/SMX were included. Patients’ clinical and microbiological outcomes were compared between oral TMP/SMX and ertapenem treatment groups.Results: A total of 103 patients were included, 21 of whom had been treated with TMP/SMX, whereas 82 with ertapenem. Clinical outcomes between the two groups were not significantly different (TMP/SMX: 90.5%; ertapenem: 84.1%, p = 0.73). The microbiological cure rate was higher in the TMP/SMX group than in the ertapenem group (90.5% vs 58.5%, respectively, p = 0.01). The mean duration of hospitalization was significantly shorter in the TMP/SMX group than in the ertapenem group (8.00 ± 10.50 days vs 14.00 ± 37.00 days, p = 0.07). The mean duration of antibiotic treatment was longer in the ertapenem group than in the TMP/SMX group (16.45 ± 4.77 vs 12.76 ± 5.37 days, p = 0.006).Conclusion: For susceptible pathogens, TMP/SMX may enable early discharge as an effective oral antibiotic treatment option for UTIs caused by ESBL-positive pathogens. Additionally, use of oral antibiotics can shorten hospital stays and reduce medical costs.Keywords: oral antibiotics, ESBL, UTI, TMP/SMX, outpatient treatment

Hye Jin Shi,1 Jin Seo Lee,2 Yong Kyun Cho,1 Joong Sik Eom1 1Division of Infectious Diseases, Department of Internal Medicine, Gil Medical Center, Gachon University School of Medicine, Incheon, Republic of Korea; 2Division of Infectious Diseases, Department of Internal Medicine, Kangdong Sacred Hospital, Hallym University School of Medicine, Seoul, Republic of KoreaCorrespondence: Joong Sik EomDivision of Infectious Diseases, Department of Internal Medicine, Gil Medical Center, Gachon University School of Medicine, 774 Namdongdaero, Namdong-Gu, Incheon 21565, South KoreaTel +82-32-460-2630Fax +82-32-460-4884Email helppl@gachon.ac.krPurpose: The incidences of carbapenem-resistant gram-negative bacilli (CRGNB) and vancomycin-resistant Enterococci (VRE) have increased rapidly in South Korea since 2000. The mortality rate for CRGNB or VRE bacteremia cases is higher than that for non-resistant bacteremia cases. The factors associated with higher mortality are unclear. We investigated the factors associated with mortality from CRGNB or VRE bacteremia and compared the relative risk of these factors.Patients and Methods: We retrospectively collected data from adult patients with CRGNB or VRE bacteremia. Patients were grouped according to whether they survived or died. The data from both groups were compared.Results: During the study period, 171 cases of CRGNB or VRE bacteremia were identified, of which 100 were CRGNB bacteremia cases and 71 were VRE bacteremia cases. Multivariate analysis revealed significant associations with Pitt bacteremia score (PBS) (odds ratio [OR] 1.329, 95% confidence interval [CI] 1.049– 1.684). In the multivariate analysis, negative conversion of follow-up blood culture (FUBC) was related with one-week mortality from CRGNB or VRE bacteremia (OR 17.623, 95% CI 5.726– 54.244). In the multivariate analysis of risk factors for 28-day mortality for CRGNB or VRE bacteremia, the significant risk factors were bacteremia of respiratory origin (OR 4.491, 95% CI 1.622– 12.435) and positive FUBC (OR 4.082, 95% CI 1.626– 10.204).Conclusion: Despite the high mortality rate in patients with CRGNB or VRE bacteremia, the related mortality could be predicted by independent risk factors of PBS, positive FUBC, and bacteremia of respiratory origin.Keywords: prognostic factor, carbapenem-resistant, vancomycin-resistant, bacteremia, mortality

Objective: Green tea has been widely acknowledged in Japan to induce a pleasurable mental feeling. Recent laboratory studies have suggested positive psychological effects as a result of consuming green tea. The present study examined whether green tea consumption in everyday life in Japan is associated with positive mental health.Design: A cross-sectional study was performed in February-March 2002.Setting and Subjects: The subjects of the study consisted of a general population of 600 Japanese aged 20-69 years. Responses of 380 subjects, obtained by home-visit interview, were analysed. The questionnaire inquired about consumption of brewed green tea and other beverages, perceived mental health status, lifestyle and others. The 12-item General Health Questionnaire (GHQ 12) was used for the assessment of mental ill-health (GHQ score >or=4).Results: After adjustments for age, area, perceived mental stress, lifestyle and daily caffeine intake, the consumption of brewed green tea was not statistically associated with any decrease in risk of mental ill-health among either males or females (odds ratio (OR)=0.78, 95% confidence interval (CI)=0.47-1.29 for males; OR=0.77, 95% CI=0.51-1.14 for females). Daily caffeine intake (100 mg) inclusive of green tea, black tea, coffee and other caffeine-containing beverages was associated with a higher risk of mental ill-health among females (OR=1.26, 95% CI=1.01-1.56).Conclusions: The results provide population-based evidence on the consumption of brewed green tea in everyday life and mental health, together with information on consumption patterns of various beverages and lifestyles. [ABSTRACT FROM AUTHOR]

Background: Mortality from colorectal cancer is mainly due to metastatic liver disease. Improved understanding of the molecular events underlying metastasis is crucial for the development of new methods for early detection and treatment of colorectal cancer. Loss of chromosome 8p is frequently seen in colorectal cancer and implicated in later stage disease and metastasis, although a single metastasis suppressor gene has yet to be identified. We therefore examined 8p for genes involved in colorectal cancer progression.Methods: Loss of heterozygosity analyses were used to map genetic loss in colorectal liver metastases. Candidate genes in the region of loss were investigated in clinical samples from 44 patients, including 6 with matched colon normal, colon tumour and liver metastasis. We investigated gene disruption at the level of DNA, mRNA and protein using a combination of mutation, semi-quantitative real-time PCR, western blotting and immunohistochemical analyses.Results: We mapped a 2 Mb region of 8p21-22 with loss of heterozygosity in 73% of samples; 8/11 liver metastasis samples had loss which was not present in the corresponding matched primary colon tumour. 13 candidate genes were identified for further analysis. Both up and down-regulation of 8p21-22 gene expression was associated with metastasis. ADAMDEC1 mRNA and protein expression decreased during both tumourigenesis and tumour progression. Increased STC1 and LOXL2 mRNA expression occurred during tumourigenesis. Liver metastases with low DcR1/TNFRSF10C mRNA expression were more likely to present with extrahepatic metastases (p = 0.005). A novel germline truncating mutation of DR5/TNFRSF10B was identified, and DR4/TNFRSF10A SNP rs4872077 was associated with the development of liver metastases (p = 0.02).Conclusion: Our data confirm that genes on 8p21-22 are dysregulated during colorectal cancer progression. Interestingly, however, instead of harbouring a single candidate colorectal metastasis suppressor 8p21-22 appears to be a hot-spot for tumour progression, encoding at least 13 genes with a putative role in carcinoma development. Thus, we propose that this region of 8p comprises a metastatic susceptibility locus involved in tumour progression whose disruption increases metastatic potential. [ABSTRACT FROM AUTHOR]

A unique meso Ce(III)-containing antimonotungstate, {Na(OAc)(H 2 O) 2 [Ce 4 (tar)(Htar) 2 (Sb 2 W 21 O 72 ) 2 (H 2 O) 7 ]} 2 44- ( Ce 4 tar 3 ; H 4 tar = tartaric acid), consisting of two enantiomeric parts with a butterfly-like configuration, was successfully synthesized by a one-pot in situ method and characterized. The coordination of d- or l-tar ligands induced the formation of Dawson-like {Ce 2 Sb 2 W 21 } with right or left configurations, thereby determining the d/l configurations of {Na(OAc)(H 2 O) 2 [Ce 4 (tar)(Htar) 2 (Sb 2 W 21 O 72 ) 2 (H 2 O) 7 ]} 22- . Carboxyl groups link these two enantiomeric parts with Ce(III) ions from each other around the symmetric center of the P 1̅ space group. The three types of tar ligands exhibit distinct coordination modes, and all coordinate with at least one W(VI) atom using one carboxylate oxygen atom and one α-OH. Ce 4 tar 3 represents the largest case among those meso -dl-tar-functionalized polyoxometalates. Furthermore, Ce 4 tar 3 exhibits excellent catalytic activity for synthesizing isoindolinones via the three-component reaction of 2-acetylbenzoic acids, amines, and phosphine oxides.

Background: Multimodal analgesic strategy is pivotal for enhanced recovery after surgery. The objective of this trial was to assess the effect of subanesthetic esketamine vs. placebo combined with erector spinae plane block (ESPB) vs. intercostal nerve block (ICNB) on postoperative recovery following thoracoscopic lung resection., Materials and Methods: This randomized, controlled, 2×2 factorial trial was conducted at a university hospital in Suzhou, China. One hundred adult patients undergoing thoracoscopic lung surgery were randomized to one of four groups (esketamine-ESPB, esketamine-ICNB, placebo-ESPB, and placebo-ICNB) to receive i.v. esketamine 0.3 mg/kg or normal saline placebo combined with ESPB or ICNB using 0.375% ropivacaine 20 mL. All patients received flurbiprofen axetil and patient-controlled fentanyl. The primary outcome was quality of recovery (QoR) at 24 h postoperatively, assessed using the QoR-15 scale, with a minimal clinically important difference of 6.0., Results: The median age was 57 years and 52% were female. No significant interaction effect was found between esketamine and regional blocks on QoR (P=0.215). The QoR-15 score at 24 h was 111.5±5.8 in the esketamine group vs. 105.4±4.5 in the placebo group (difference=6.1, 95% CI, 4.0-8.1; P<0.001); 109.7±6.2 in the ESPB group vs. 107.2±5.6 in the ICNB group (difference=2.5, 95% CI, 0.2-4.9; P=0.033; not statistically significant after Bonferroni correction). Additionally, esketamine resulted in higher QoR-15 scores at 48 h (difference=4.6) and hospital discharge (difference=1.6), while ESPB led to a higher QoR-15 score at 48 h (difference=3.0)., Conclusions: For patients undergoing thoracoscopic lung resection, subanesthetic esketamine improved QoR after surgery, while ICNB can be used interchangeably with ESPB as a component of multimodal analgesia., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Multimodal analgesia plays a key role in enhanced recovery after surgery. Herein, we describe a trial protocol investigating the effects of oxycodone-vs. sufentanil-based patient-controlled analgesia in combination with quadratus lumborum block (QLB) vs. transverse abdominis plane block (TAPB) on quality of recovery following major laparoscopic gastrointestinal surgery., Methods: and analysis: This is a prospective, randomized, controlled clinical trial with a 2 × 2 factorial design. A total of 120 adult patients undergoing laparoscopic major gastrointestinal surgery will be randomized, in a 1:1:1:1 ratio, to receive one of two patient-controlled analgesia regimens (based on oxycodone or sufentanil) and one of two regional blocks (QLB or TAPB). The primary outcome measure of this trial is the quality of recovery at 24 h after surgery, assessed using the 15-item quality of recovery (QoR-15) scale. The secondary outcomes include QoR-15 scores at 48 and 72 h after surgery; visceral and incisional pain at rest and while coughing at 1, 6, 24 and 48 h postoperatively; analgesic consumption within 0-24 h and 24-48 h postoperatively; need for rescue analgesia; postoperative flatus time; postoperative adverse events (sedation, nausea and vomiting, use of antiemetics, respiratory depression, and dizziness); and length of postoperative hospital stay., Discussion: The results of this trial will provide evidence for the optimal multimodal analgesic strategy to improve the quality of recovery for patients undergoing laparoscopic major gastrointestinal surgery., Trial Registration: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR2400080766)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: Urinary tract infection is one of the most prevalent bacterial infectious diseases in outpatient treatment, and 50-80% of women experience it more than once, with a recurrence rate of 40-50% within a year; consequently, preventing re-hospitalization of patients is critical. However, in the field of urology, no research on the analysis of the re-hospitalization status for urinary tract infections using machine learning algorithms has been reported to date. Therefore, this study uses various machine learning algorithms to analyze the clinical and nonclinical factors related to patients who were re-hospitalized within 30 days of urinary tract infection., Methods: Data were collected from 497 patients re-hospitalized for urinary tract infections within 30 days and 496 patients who did not require re-hospitalization. The re-hospitalization factors were analyzed using four machine learning algorithms: gradient boosting classifier, random forest, naive Bayes, and logistic regression., Results: The best-performing gradient boosting classifier identified respiratory rate, days of hospitalization, albumin, diastolic blood pressure, blood urea nitrogen, body mass index, systolic blood pressure, body temperature, total bilirubin, and pulse as the top-10 factors that affect re-hospitalization because of urinary tract infections. The 993 patients whose data were collected were divided into risk groups based on these factors, and the re-hospitalization rate, days of hospitalization, and medical expenses were observed to decrease from the high- to low-risk group., Conclusions: This study showed new possibilities in analyzing the status of urinary tract infection-related re-hospitalization using machine learning. Identifying factors affecting re-hospitalization and incorporating preventable and reinforcement-based treatment programs can aid in reducing the re-hospitalization rate and average number of days of hospitalization, thereby reducing medical expenses., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

To study a new method for establishing animal models of prenatal bronchopulmonary dysplasia (BPD), we used lung ultrasound score (LUS) to semi-quantitatively assess the severity of lung lesions in model rats. Lipopolysaccharide (LPS) was injected into the right lung of the fetus of the rat under ultrasound-guided, and the right lung of the neonates were scanning for LUS. Specimens were collected for pathological scoring and detection of pulmonary surfactant-associated glycoprotein (SP)-C and vascular endothelial growth factor (VEGF) expression quantity. The correlation between LUS and pathological scores was analyzed. (1) The animal models were consistent with the pathological manifestations of BPD. (2) It showed a strong positive correlation between LUS and pathological scores in animal models (r = 0.84, P < 0.005), and the expression quantity of SP-C and VEGF in lung tissue were decreased (both P < 0.05). Animal models established by ultrasound-guided puncture of the lung of rats and injection of LPS were consistent with the manifestation of BPD. This method could be used to establish animal models of BPD before birth, and the severity of BPD could be assessed by using LUS., (© 2024. The Author(s).)

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Chronic stress leads to social avoidance and anhedonia in susceptible individuals, a phenomenon that has been observed in both human and animal models. Nevertheless, the underlying molecular mechanisms underpinning stress susceptibility and resilience remain largely unclear. There is growing evidence that epigenetic histone deacetylase (HDAC) mediated histone acetylation is involved in the modulation of depressive-related behaviors. We hypothesized that histone deacetylase 5 (HDAC5), which is associated with stress-related behaviors and antidepressant response, may play a vital role in the susceptibility to chronic stress. In the current study, we detected the levels of HDAC5 and acetylation of histone 4 (H4) in the hippocampus subsequent to chronic social defeat stress (CSDS) in C57BL/6J mice. We found that CSDS induces a notable increase in HDAC5 expression, concomitant with a reduction in the acetylation of histone H4 at lysine 12 (H4K12) in the hippocampus of susceptible mice. Meanwhile, intrahippocampal infusion of HDAC5 shRNA or HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) both reversed the depression susceptibility in susceptible mice that subjected to CSDS. Furthermore, HDAC5 overexpression was sufficient to induce depression susceptibility following microdefeat stress, accompanied by a significant reduction in H4K12 level within the hippocampus of mice. Additionally, the Morris water maze (MWM) results indicated that neither CSDS nor HDAC5 exerted significant effects on spatial memory function in mice. Taken together, these investigations indicated that HDAC5-modulated histone acetylation is implicated in regulating the depression susceptibility, and may be serve as potential preventive targets for susceptible individuals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Postoperative sleep disturbance (PSD) occurs frequently in patients who undergo major abdominal surgical procedures. Dexmedetomidine is a promising agent to improve the quality of sleep for surgical patients. We designed this trial to investigate the effects of two different doses of intraoperative dexmedetomidine on the occurrence of PSD in elderly patients who have major abdominal surgery., Methods: In this randomized, double-blind, controlled trial, 210 elderly patients aged ≥65 years will be randomized, with an allocation ratio of 1:1:1, to two dexmedetomidine groups (intraoperative infusion of 0.3 or 0.6 μg/kg/h) and a normal saline placebo group. The primary endpoint is the occurrence of PSD on the first night after surgery, assessed using the Athens Insomnia Scale. The secondary endpoints are (1) the incidence of PSD during the 2nd, 3rd, 5th, 7th, and 30th nights postoperatively; (2) pain at rest and on movement at 24 and 48 h postoperatively, assessed using the Numerical Rating Scale; (3) the incidence of postoperative delirium during 0-7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method; (4) depressive symptoms during 0-7 days postoperatively or until hospital discharge, assessed using the 15-items Geriatric Depression Scale; and (5) quality of recovery on postoperative days 1, 2, and 3, assessed using the 15-items Quality of Recovery Scale. Patients' sleep data will also be collected by Xiaomi Mi Band 7 for further analysis., Discussion: The findings of this trial will provide clinical evidence for improving the quality of sleep among elderly patients undergoing major abdominal surgery., Ethics and Dissemination: This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University (No. 2023-160). The results will be published in a peer-reviewed journal., Trial Registration: Chinese Clinical Trial Registry (ChiCTR2300073163)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Objectives: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China., Methods: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed., Results: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis., Conclusions: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in depression is a topic of debate, and the underlying mechanisms remain largely unclear. We now elucidate hippocampal excitation-inhibition (E/I) balance underlies the regulatory effects of 5-HT2CR in depression. Molecular biological analyses showed that chronic mild stress (CMS) reduced the expression of 5-HT2CR in hippocampus. We revealed that inhibition of 5-HT2CR induced depressive-like behaviors, reduced GABA release and shifted the E/I balance towards excitation in CA3 pyramidal neurons by using behavioral analyses, microdialysis coupled with mass spectrum, and electrophysiological recording. Moreover, 5-HT2CR modulated neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction through influencing intracellular Ca2+ release, as determined by fiber photometry and coimmunoprecipitation. Notably, disruption of nNOS-CAPON by specific small molecule compound ZLc-002 or AAV-CMV-CAPON-125C-GFP, abolished 5-HT2CR inhibition-induced depressive-like behaviors, as well as the impairment in soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly-mediated GABA vesicle release and a consequent E/I imbalance. Importantly, optogenetic inhibition of CA3 GABAergic neurons prevented the effects of AAV-CMV-CAPON-125C-GFP on depressive behaviors in the presence of 5-HT2CR antagonist. Conclusively, our findings disclose the regulatory role of 5-HT2CR in depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To investigate the influence of prenatal stressful life event (SLE) exposure on child emotional and behavioral problem at age 2-6 years and identify the most risk exposure period. Methods: A total of 2 524 mother-child pairs were selected from Shanghai Maternal-Child Pairs Cohort based on pregnant women form 2016 to 2018 in Shanghai. Prenatal SLE exposure was assessed by Life Events Scale for Pregnant Women Questionnaire during the first and third trimester of pregnancy. Child emotional and behavioral problem was evaluated by Strengths and Difficulties Questionnaire at age 2-6 years. Multivariate binary logistic regression model and generalized estimating equation were conducted to quantify the association between prenatal SLE exposure and child emotional and behavioral problem at age 2-6 years, and identify the pregnancy period with strongest adverse effect. Results: The 2 524 mother-child pairs were divided into 4 groups: group with consistent low exposure to SLE (61.8%), group with high exposure to SLE in the first trimester (13.2%), group with high exposure to SLE in the third trimester (13.2%) and group with consistent high exposure to SLE (11.8%). The detection rates of emotional problem, hyperactivity, peer interaction problem and total difficulty score in children aged 3-6 years were highest in the group with consistent high exposure to SLE. Generalized estimating equation analysis showed that after controlling the confounding factors, compared with the consistent low exposure group, the children in the group with high exposure to SLE in the first trimester had significant increased risk for conduct problem at age 2-6 years (a OR =1.41, 95% CI :1.07-1.87). The children in the group with consistent high exposure to SLE were at increased risk for emotional problem, peer interaction problem, and high total difficulty score with the a OR of 1.41 (95% CI : 1.09-1.83), 1.46 (95% CI : 1.15-1.86) and 1.51(95% CI : 1.17-1.93). Conclusion: These findings indicated that prenatal exposure to SLE have adverse effect on child emotional and behavioral problem at age 2-6 years, especially the exposure in the first trimester.

Cytomegalovirus (CMV) is the most important opportunistic viral pathogen in solid organ transplant (SOT) recipients. The Korean guideline for the prevention of CMV infection in SOT recipients was developed jointly by the Korean Society for Infectious Diseases and the Korean Society of Transplantation. CMV serostatus of both donors and recipients should be screened before transplantation to best assess the risk of CMV infection after SOT. Seronegative recipients receiving organs from seropositive donors face the highest risk, followed by seropositive recipients. Either antiviral prophylaxis or preemptive therapy can be used to prevent CMV infection. While both strategies have been demonstrated to prevent CMV infection post-transplant, each has its own advantages and disadvantages. CMV serostatus, transplant organ, other risk factors, and practical issues should be considered for the selection of preventive measures. There is no universal viral load threshold to guide treatment in preemptive therapy. Each institution should define and validate its own threshold. Valganciclovir is the favored agent for both prophylaxis and preemptive therapy. The evaluation of CMV-specific cell-mediated immunity and the monitoring of viral load kinetics are gaining interest, but there was insufficient evidence to issue recommendations. Specific considerations on pediatric transplant recipients are included., Competing Interests: WBP is associate editor and NJK, LS-O, KRP are editorial board of Infect Chemother; however, they did not involve in the peer reviewer selection, evaluation, and decision process of this article., (Copyright © 2024 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Background: Previous studies demonstrated a controversial relationship between sarcopenia (SP) and osteoarthritis (OA) and their genetic causality is unclear. Thus, we conducted a Mendelian randomization (MR) analysis to evaluate the possible causal association between sarcopenia-related traits (appendicular lean mass (ALM), grip strength, usual walking pace) and OA. Method: We used pooled genetic data from the UK Biobank for ALM(n = 450,243), left-hand grip strength (n = 461,026), right-hand grip strength (n = 461,089) and usual walking pace (n = 459,915). Moreover, summary statistics for OA were obtained from the latest study conducted by the Genetics of Osteoarthritis Consortium, including all OA (n = 826,690), hand OA (n = 303,7782), hip OA (n = 353,388) and knee OA (n = 396,054). The primary method for estimating causal effects was the inverse-variance weighted (IVW) method, with the utilizing of false discovery rate adjusted p values ( P FDR ). Additional MR methods such as MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median were employed as supplementary analyses. Results: We discovered ALM (odds ratio (OR) = 1.103, 95% confidence interval (CI) = 1.052-1.156, P FDR = 2.87E-04), hand grip strength (left, IVW OR = 0.823, 95% CI = 0.712 to 0.952, P FDR = 0.020; right, OR = 0.826, 95% CI = 0.718 to 0.950, P FDR = 0.020), and usual walking pace (OR = 0.339, 95% CI = 0.204 to 0.564, P FDR = 2.38E-04) were causally associated with OA risk. In the reverse MR analysis, we identified a causal effect of OA on ALM (β = -0.258, 95% CI = -0.369 to 0.146, P FDR = 0.6.07E-06), grip strength (left, β = -0.064, 95% CI = -0.104 to 0.024, P FDR = 0.002; right, β = -0.055, 95% CI = -0.095 to 0.014, P FDR = 0.008), and usual walking pace (β = -0.104, 95% CI = -0.147 to 0.061, P FDR = 1.61E-05). Conclusion: This present study suggests an obvious causality of SP on OA, with condition exhibiting site-specific effects, while evidence was also provided for the causal effect of OA on SP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jia, Deng, Su, Shi, Qin, Yu, Yin, Liu and Shi.)

Scatophagus argus is an important marine culture fish in South and South-East Asia, including Southeast coastal areas of China. Artificial propagation technology for S. argus is not optimum; thus further studies on its reproduction biology are required. Although previous studies have shown that leptin (Lep) can regulate fish reproduction, the role of lep genes in S. argus is unknown. Herein, in silico analysis showed that S. argus has two lep genes (lepa and lepb). Protein 3D-structure prediction showed that Lepa has four α-helices (similar to mammals), while Lepb only has three. Tissue distribution analysis showed that lepa is highly expressed in the liver, whereas lepb was not detected in any tissue. Notably, lepr was expressed in all tissues. Lepa mRNA expression levels in the liver and serum Lep, estradiol (E 2 ) and vitellogenin (Vtg) levels of female fish were significantly higher in ovaries at stage IV than in ovaries at stage II. Serum E 2 levels were significantly positively correlated with Vtg levels in female fish at different development stages, while serum E 2 was not correlated with Lep levels. Consistently, in vitro incubation of the liver with E 2 significantly up-regulated vtga, while it did not affect lepa expression. Recombinant Lep (10 nM) significantly up-regulated chicken gonadotropin-releasing hormone (cGnRH/GnRH-II) in the hypothalamus and GnRH receptor (GnRHR) and luteinizing hormone beta (Lhb) in the pituitary. These results suggest that lepa regulates female reproduction in S. argus., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To compare physical activity and its influencing factors in patients with chronic obstructive pulmonary disease (COPD) between China and the United Kingdom. Methods: We analyzed baseline data from China Kadoorie Biobank and the United Kingdom Biobank among COPD patients who were diagnosed with a one-second rate (FEV 1 /FVC) less than 70%. Physical activity level was calculated as metabolic equivalent (MET) and divided into three levels: low, medium, and high, according to tertiles stratified by gender and age. Multiple logistic regression was used to estimate OR s and 95% CI s for COPD and Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade about physical activity level, and subgroup analysis was conducted. Results: A total of 506 073 Chinese adults and 231 884 British adults were included. After adjusting for potential confounders, COPD was associated with lower physical activity levels in both Chinese and British COPD patients, with OR (95% CI ) of 1.07(1.03-1.10) and 1.03(1.01-1.06) compared with non COPD patients, respectively. The GOLD grade was inversely correlated with physical activity level, particularly in a dose-response manner in the CKB population (trend test P <0.001). The negative relationship was stronger among the elderly, people with less education and lower economic status, and those with a smoking or chronic disease history. Chinese rural COPD patients were at high risk of decline of physical activity. Conclusions: Physical activity is inversely related to COPD, with a dose-response connection to GOLD grade. Therefore, physical activity maintenance and improvement should be encouraged and promoted in COPD patients, especially in high-risk groups.

Background: Nocardiosis is a rare, but potentially life-threatening condition. It is difficult to diagnose, and bacterial culture identification can be time consuming. We investigated the characteristics of nocardiosis and the suitability of the treatment approach in Korea., Materials and Methods: This retrospective study was conducted at 5 medical institutions between 2011 and 2021. We reviewed the medical records of patients with microbiologically confirmed nocardiosis. Appropriate antibiotic selection was defined as follows: (1) selecting antibiotics according to the species, (2) if the species of Nocardia was unknown, trimethoprim-sulfamethoxazole-based therapy or linezolid-based therapy was administered, and (3) selection of antibiotics using the antibiotic susceptibility test. The appropriate treatment periods for antibiotics were defined as treatment maintained from 3 to 12 months, depending on involvement of the organs. Descriptive analysis and Fisher exact test were used. Statistical significance was set at P -values of <0.05., Results: Thirty patients were enrolled. Of these patients, 18 (60.0%) were male. The median age was 70.5 years. Among the diagnosed patients, 12 (40.0%) had an immunocompromised status. Eight (30.0%) patients received optimal treatment for the appropriate treatment period. Appropriate dosing duration was observed in 3 of the 12 (25.0%) immunocompromised patients. There was no significant difference between the presence or absence of immunosuppression and the adequacy of treatment for nocardiosis ( P = 1.000). Skin and soft tissue (14 patients) were most frequently involved in this study. Nocardia species (spp.) were isolated from culture at a median of 6.0 days. There were 7 cases with N. farcinica (23.3%)., Conclusion: We found that 60.0% of the patients with nocardiosis did not have an immunocompromised status. Further, 26.7% of the total patients received adequate treatment for nocardiosis. The reasons for suboptimal management of nocardiosis in Korea are presumed to be diagnostic difficulties, lack of awareness about nocardiosis, and difficulties in selecting antibiotics for Nocardia spp. among clinicians. The lack of antibiotic susceptibility tests for Nocardia spp. could be the source of these problems. Nocardiosis should be suspected in cases of recurrent infections with skin and soft tissue, musculoskeletal, or respiratory system involvement with or without an immunocompromised status. Clinical microbiological support is required for the diagnosis and selection of antibiotics in Korea. High clinical index of suspicion and clinical microbiological support are required for the accurate diagnosis of nocardiosis in Korea., Competing Interests: No conflict of interest., (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Background: The purpose of this study was to investigate the mechanism of sanguinarine (SAN) against nasopharyngeal carcinoma (NPC) by means of network pharmacology, molecular docking technique, and experimental verification., Methods: The SAN action targets were predicted using the Swiss Target Prediction database, the related NPC targets were determined using the GEO database, and the intersection of drug and disease pathway targets were considered to be the potential targets of SAN against NPC. The target-protein interaction network map was constructed using the STRING database, and the core target genes of SAN against NPC were obtained via topological network analysis. "R" language gene ontology (GO) function and Kyoto encyclopedia of genes and genome (KEGG) pathway enrichment analyses were used to dock the core target genes with SAN with the help of AutodockVina. Cell proliferation was detected using MTT and xCELLigence real-time cell analysis. Apoptosis was identified via Hoechst 33342 staining, JC-1 mitochondrial membrane staining, and annexin V-FITC/PI double fluorescence staining, while protein expression was quantified using western blotting., Results: A total of 95 SAN against NPC targets were obtained using target intersection, and 8 core targets were obtained by topological analysis and included EGFR, TP53, F2, FN1, PLAU, MMP9, SERPINE1, and CDK1. Gene ontology enrichment analysis identified 530 items, and 42 items were obtained by Kyoto encyclopedia of genes and genome pathway enrichment analysis and were mainly related to the PI3K/AKT, MAPK, and p53 signaling pathways. Molecular docking results showed that SAN had good binding activity to the core target. SAN inhibited the proliferation of NPC cells, induced apoptosis, reduced the expression levels of survivin and Bcl2, and increased the expression levels of Bax and cleaved caspase-8. It also decreased the expression levels of the key proteins p-c-Raf, p-MEK, and p-ERK1/2 in the MAPK/ERK signaling pathway in NPC cells., Conclusion: SAN inhibits the proliferation and induces the apoptosis of NPC cells through the MAPK/ERK signaling pathway., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Currently, clinical analysis of male infertility mainly relies on parameters of semen and sperm cells. However, the high diagnostic failure rates indicate that the current assessment methods are not sufficient and a new approach to evaluating sperm function still needs to be developed. Here we explored the feasibility of single-cell inductively coupled plasma mass spectrometry (sc-ICP-MS)-derived profiles to determine the elemental characteristics in viable capacitated sperm under normal and deficient conditions. To validate the measurements, we used male sterile Pmca4-knockout (KO) mice with impaired calcium clearance, known to be dysregulated due to loss of calcium efflux capacity during sperm capacitation. Consistently, we observed significantly increased calcium intensities in Pmca4-KO sperm upon capacitation stimulation compared with control sperm from the caudaepididymides of wild-type control (WT) mice. More importantly, we explored that the characteristic signatures of calcium intensities in individual spikes derived from sc-ICP-MS was consistent with the dynamics of relative calcium levels in single sperm reported in the literature. Prominent alterations were also observed in the dynamic signatures of sc-ICP-MS-derived profiles of essential elements, particularly the redox-labile elements including copper, iron, manganese, selenium, and zinc in Pmca4-KO sperm compared to WT controls. Therefore, our study demonstrates that elementomics of sc-ICP-MS-derived signals can reveal ionic dysregulation in plasma membrane Ca2+-ATPase isoform 4 protein deficient sperm, and that sc-ICP-MS assay can be applied for functional analysis of viable sperm in functional activities, such as capacitation stimulation. We propose that cell elementomics can be used as an alternative approach to assessing sperm quality and male fertility at the single-cell level., (© The Author(s) 2023. Published by Oxford University Press.)

We present a summary of the evidence on testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and organ procurement from deceased donors and provide recommendations based on current clinical data and the guidelines from major transplant organizations. Because of the limited historical experience with coronavirus disease 2019 (COVID-19), certain recommendations in this document are based on theoretical rationales rather than clinical data. The recommendations in this manuscript may be subject to revision as subsequent clinical studies provide definitive evidence regarding COVID-19 in organ procurement.

Background: To explore the independent association between lumbar endplate damage and bone mineral density (BMD) in patients with degenerative disc disease (DDD)., Methods: This retrospective investigation was based out of a prospectively collected database from the Affiliated Kunshan Hospital of Jiangsu University. Data from 192 DDD patients, collected between December 2018 and January 2022, were chosen for the final analysis. The average total endplate score (TEPS) of lumbar(L) 1-L4 was assessed by magnetic resonance imaging (MRI), and represents the extent of endplate damage. Osteoporosis severity was assessed via the L1-L4 BMD evidenced by dual-energy x-ray absorptiometry (DXA). Other analyzed information included gender, age, body mass index (BMI), and osteophyte score (OSTS). Uni- and multivariate linear regression analyses were employed to evaluate the association between average TEPS and BMD of L1-L4. Moreover, the generalized additive model (GAM) was employed for non-linear association analysis., Results: Upon gender, age, BMI, and OSTS adjustments, a strong independent inverse relationship was observed between average TEPS and BMD (β, -0.021; 95% CI, -0.035 to -0.007, P-value = 0.00449). In addition, the gender stratification analysis revealed a linear relationship in males, and a non-linear relationship in females. Specifically, there was a significantly stronger negative relationship between average TEPS and BMD in females, when the average TEPS was < 3.75 (β, -0.063; 95% CI, -0.114 to -0.013; P-value = 0.0157). However, at an average TEPS > 3.75, the relationship did not reach significance (β, 0.007; 95% CI, -0.012 to 0.027; P-value = 0.4592)., Conclusions: This study demonstrated the independent negative association between average TEPS and BMD values of L1-L4. Upon gender stratification, a linear relationship was observed in males, and a non-linear association in females. The findings reveal that patients with osteoporosis or endplate damage require more detailed examinations and treatment regimen., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Post-induction hypotension (PIH) is a common event in elderly surgical patients and is associated with increased postoperative morbidity and mortality. This study aims to develop and validate a PIH prediction model for elderly patients undergoing elective non-cardiac surgery to identify potential PIH in advance and help to take preventive measures., Methods and Analysis: A total of 938 elderly surgical patients (n=657 for development and internal validation, n=281 for temporal validation) will be continuously recruited at The First Affiliated Hospital of Soochow University in Suzhou, China. The main outcome is PIH during the first 15 min after anaesthesia induction or before skin incision (whichever occurs first). We select candidate predictors based on published literature, professional knowledge and clinical expertise. For model development, we will use the least absolute shrinkage and selection operator regression analysis and multivariable logistic regression. For internal validation, we will apply the bootstrapping technique. After model development and internal validation, temporal validation will be conducted in patients recruited in another time period. We will use the discrimination, calibration and max-rescaled Brier score in the temporal validation cohort. Furthermore, the clinical utility of the prediction model will be assessed using the decision curve analysis, and the results will be presented in a nomogram and a web-based risk calculator., Ethics and Dissemination: Ethical approval was obtained from the Ethics Committee of the First Affiliated Hospital of Soochow University (Approval No. 2023-012). This PIH risk prediction model will be published in a peer-reviewed journal., Trial Registration Number: ChiCTR2200066201., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Schools play an organizational role in managing myopia-related behavioral habits among students. We evaluated the effects of school myopia management measures on myopia onset and progression in a school-based prospective 1-year observational study., Methods: In total, 8319 children from 26 elementary schools were included. Online questionnaire completed by a parent, in which school myopia management experience including outdoor activities in recess or physical education class, teachers' supervision, and teaching facilities. Variables were defined as implemented well or poorly, according to the Comprehensive Plan to Prevent Myopia among Children and Teenagers. Children underwent ophthalmic examinations, and the incidence and progression of myopia from 2019 to 2020 were estimated. Multilevel logistic regression models were constructed to analyze the association between school management measures and myopia development in 8,9 years and 10,11 years students., Results: From 2019 to 2020, the incidence of myopia among primary school students was 36.49%; the mean difference of spherical equivalent in myopic children was - 0.29 ± 1.22 diopters. The risk of incident myopia was reduced by 20% in 8,9 years participants with well-implemented class recess compared with those with poorly implemented class recess (adjusted odds ratio [aOR]: 0.80, p = 0.032). PE outdoor time was significantly associated with myopia incidence in 10,11 years students (aOR: 0.76, p = 0.043). Compared with poorly implemented reading and writing posture, desk and chair height, 10,11 participants with well-implemented desk and chair height were less likely to have rapid myopic progression (p = 0.029, p = 0.022)., Conclusion: In Shanghai, children's myopia is associated with better implementation of school myopia management measures. The present findings suggest that outdoor activities during class recess or PE class, providing suitable desks and chairs, and adequate instruction in reading and writing postures might protect against pathological eye growth. An age-specific myopia prevention and control programs in school is of primary importance., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Organic-inorganic hybrid metal halides for high-temperature phase transition have become increasingly popular owing to their wide operating temperature range in practical applications, e.g. , energy storage, permittivity switches and opto-electronic devices. This paper describes the subtle assembly of two new hybrid perovskite crystals, [Cl-C 6 H 4 -(CH 2 ) 2 NH 3 ] 2 CdX 4 (X = Br 1; Cl 2), undergoing high- T reversible phase transformations around 335 K/356 K. Differential scanning calorimetry (DSC), differential thermal analysis (DTA) and VT PXRD tests uncover their reversible first-order phase transition behaviors. Furthermore, the compounds exhibit switchable dielectricity near T , making them potential dielectric switching materials. Hirshfeld surface analysis well discloses a distinct difference in hydrogen-bonding interaction between 1 and 2. UV spectra and computational analysis demonstrate that the compounds are a type of direct-band-gap semiconductor. This research will contribute an effective approach to the structure and development of multifunctional molecular hybrid crystals.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused the death of thousands of patients worldwide. Although age is known to be a risk factor for morbidity and mortality in COVID-19 patients, critical illness or death is occurring even in the younger age group as the epidemic spreads. In early 2022, omicron became the dominant variant of the COVID-19 virus in South Korea, and the epidemic proceeded on a large scale. Accordingly, this study aimed to determine whether young adults (aged ≤ 50 years) with critical COVID-19 infection during the omicron period had different characteristics from older patients and to determine the risk factors for mortality in this specific age group., Methods: We evaluated 213 critical adult patients (high flow nasal cannula or higher respiratory support) hospitalized for polymerase chain reaction-confirmed COVID-19 in nine hospitals in South Korea between February 1, 2022 and April 30, 2022. Demographic characteristics, including body mass index (BMI) and vaccination status; underlying diseases; clinical features and laboratory findings; clinical course; treatment received; and outcomes were collected from electronic medical records (EMRs) and analyzed according to age and mortality., Results: Overall, 71 critically ill patients aged ≤ 50 years were enrolled, and 142 critically ill patients aged over 50 years were selected through 1:2 matching based on the date of diagnosis. The most frequent underlying diseases among those aged ≤ 50 years were diabetes and hypertension, and all 14 patients who died had either a BMI ≥ 25 kg/m² or an underlying disease. The total case fatality rate among severe patients (S-CFR) was 31.0%, and the S-CFR differed according to age and was higher than that during the delta period. The S-CFR was 19.7% for those aged ≤ 50 years, 36.6% for those aged > 50 years, and 38.1% for those aged ≥ 65 years. In multivariate analysis, age (odds ratio [OR], 1.084; 95% confidence interval [CI], 1.043-1.127), initial low-density lipoprotein > 600 IU/L (OR, 4.782; 95% CI, 1.584-14.434), initial C-reactive protein > 8 mg/dL (OR, 2.940; 95% CI, 1.042-8.293), highest aspartate aminotransferase > 200 IU/L (OR, 12.931; 95% CI, 1.691-98.908), and mechanical ventilation implementation (OR, 3.671; 95% CI, 1.294-10.420) were significant independent predictors of mortality in critical COVID-19 patients during the omicron wave. A similar pattern was shown when analyzing the data by age group, but most had no statistical significance owing to the small number of deaths in the young critical group. Although the vaccination completion rate of all the patients (31.0%) was higher than that in the delta wave period (13.6%), it was still lower than that of the general population. Further, only 15 (21.1%) critically ill patients aged ≤ 50 years were fully vaccinated. Overall, the severity of hospitalized critical patients was significantly higher than that in the delta period, indicating that it was difficult to find common risk factors in the two periods only with a simple comparison., Conclusion: Overall, the S-CFR of critically ill COVID-19 patients in the omicron period was higher than that in the delta period, especially in those aged ≤ 50 years. All of the patients who died had an underlying disease or obesity. In the same population, the vaccination rate was very low compared to that in the delta wave, indicating that non-vaccination significantly affected the progression to critical illness. Notably, there was a lack of prescription for Paxlovid for these patients although they satisfied the prescription criteria. Early diagnosis and active initial treatment was necessary, along with the proven methods of vaccination and personal hygiene. Further studies are needed to determine how each variant affects critically ill patients., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

PIWI-clade proteins harness piRNAs of 24-33 nt in length. Of great puzzles are how PIWI-clade proteins incorporate piRNAs of different sizes and whether the size matters to PIWI/piRNA function. Here we report that a PIWI-Ins module unique in PIWI-clade proteins helps define the length of piRNAs. Deletion of PIWI-Ins in Miwi shifts MIWI to load with shorter piRNAs and causes spermiogenic failure in mice, demonstrating the functional importance of this regulatory module. Mechanistically, we show that longer piRNAs provide additional complementarity to target mRNAs, thereby enhancing the assembly of the MIWI/eIF3f/HuR super-complex for translational activation. Importantly, we identify a c.1108C>T (p.R370W) mutation of HIWI (human PIWIL1) in infertile men and demonstrate in Miwi knock-in mice that this genetic mutation impairs male fertility by altering the property of PIWI-Ins in selecting longer piRNAs. These findings reveal a critical role of PIWI-Ins-ensured longer piRNAs in fine-tuning MIWI/piRNA targeting capacity, proven essential for spermatid development and male fertility., (© 2023. Science China Press.)

Background: Medications are biologically plausible and potentially modifiable risk factors for delirium. Therapies for delirium might involve more specific strategies such as avoiding the use of delirium-inducing drugs to reduce the incidence of delirium. The association between opioid exposure within 24 hours prior to delirium assessment and the risk of delirium was studied., Materials and Methods: Using three large databases, the MIMIC III v1.4, MIMIC-IV v0.4 and eICU Collaborative Research, we performed a multicenter, observational cohort study with two cohorts to estimate the relative risks of outcomes among patients administered opioids within 24 hours prior to delirium assessment. Propensity score matching was performed to generate a balanced 1 : 1 matched cohort and to identify potential prognostic factors. The outcomes included mortality, length of intensive care unit (ICU) stay, length of hospitalization, and odds of being discharged home., Results: Propensity matching successfully balanced the covariates for the 9,529 patients in each group. Opioid use was associated with a significantly higher risk for delirium than not using opioids (p < 0.001). Additionally, treatment with opioids was associated with higher mortality and a longer ICU stay (p < 0.001) than treatment without opioids. However, patients treated with opioids were more likely to be discharged home (p < 0.001)., Conclusion: Opioids may be an independent risk factor for delirium in critically ill patients.

Background: We aimed to identify the genes of 35 pathogens, including viruses, bacteria, and protozoa that cause waterborne infectious diseases, and to assess the feasibility of a wastewater-based surveillance system., Materials and Methods: Wastewater was aseptically sampled once a month from 2 sites. A total of 1 L of wastewater from each site underwent 0.2 µm filtration to generate the sample A. Subsequently, 200 ul of the filtered water was ultra-filtered and concentrated to generate the sample B, which was mixed with sample A in a 1:1 ratio. We performed a Filmarray ® Gastrointestinal (GI) panel (BioFire Diagnnostics', Salt Lake City, UT, USA) test to simultaneously detect 13 enterobacteria, 5 enterovirus, and 4 protozoa. RNA was extracted to assess 18 types of viruses., Results: Severe acute respiratory syndrome coronavirus 2 adenovirus, bocavirus, and rhinovirus was detected at both site. Norovirus GI/GII was continuously detected at both sites. Moreover, adenovirus, group A rotaviruses, and hepatitis A virus were frequently detected; however, hepatitis E virus was absent at either site. Campylobacter, enteroaggregative Escherichia coli , enterotoxigenic E. coli , Shiga toxin-producing E. coli , and Clostridioides difficile toxin A/B were detected at both sites. Giardia lamblia was also detected in both sites., Conclusion: We analyze multiple infectious disease pathogens under sample surveillance with incidence. Further in-depth studies on wastewater-based surveillance will be feasible and important., Competing Interests: No conflict of interest., (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Anxiety disorders are currently a major psychiatric and social problem, the mechanisms of which have been only partially elucidated. The hippocampus serves as a major target of stress mediators and is closely related to anxiety modulation. Yet so far, its complex anatomy has been a challenge for research on the mechanisms of anxiety regulation. Recent advances in imaging, virus tracking, and optogenetics/chemogenetics have permitted elucidation of the activity, connectivity, and function of specific cell types within the hippocampus and its connected brain regions, providing mechanistic insights into the elaborate organization of the hippocampal circuitry underlying anxiety. Studies of hippocampal neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, dopaminergic, and serotonergic systems, have contributed to the interpretation of the underlying neural mechanisms of anxiety. Neuropeptides and neuroinflammatory factors are also involved in anxiety modulation. This review comprehensively summarizes the hippocampal mechanisms associated with anxiety modulation, based on molecular, cellular, and circuit properties, to provide tailored targets for future anxiety treatment., (© 2023. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Since the switchable spontaneous polarization of ferroelectric materials endows it with many useful properties such as a large pyroelectric coefficient, switchable spontaneous polarization, and semiconductor, it has a wide range of application prospects, and the research of high-performance molecular ferroelectric materials has become a hot spot. We obtained a 0D organic-inorganic hybrid ferroelectric [(CH 3 ) 3 NCH 2 CH 2 CH 3 ] 2 FeCl 4 ( 1 ) with well-defined ferroelectric domains and excellent domain inversion and exhibited a relatively large spontaneous polarization ( P s = 9 μC/m -2 ) and a Curie temperature ( T c ) of 394 K. Furthermore, compound 1 belongs to the non-centrosymmetrical space group Cmc 2 1 and has a strong second-harmonic generation signal. Interestingly, we also performed magnetic tests on 1 , which confirmed that it is a magnetic material. This work provides clues for exploring the application of high-performance molecular ferroelectric materials in future multifunctional smart devices.

Advanced paternal age has been overlooked, and its effect on fertility remains controversial. Previous studies have focused mainly on intracytoplasmic sperm injection (ICSI) cycles in men with oligozoospermia. However, few studies have reported on men with semen parameters within reference ranges. Therefore, we conducted a retrospective cohort study analyzing the reproductive outcomes of couples with non-male-factor infertility undergoing in vitro fertilization (IVF) cycles. In total, 381 cycles included were subgrouped according to paternal age (<35-year-old, 35-39-year-old, or ≥40-year-old), and maternal age was limited to under 35 years. Data on embryo quality and clinical outcomes were analyzed. The results showed that fertilization and high-quality embryo rates were not significantly different (all P > 0.05). The pregnancy rate was not significantly different in the 35-39-year-old group (42.0%; P > 0.05), but was significantly lower in the ≥40-year-old group (26.1%; P < 0.05) than that in the <35-year-old group (40.3%). Similarly, the implantation rate significantly decreased in the ≥40-year-old group (18.8%) compared with that in the <35-year-old group (31.1%) and 35-39-year-old group (30.0%) (both P < 0.05). The live birth rate (30.6%, 21.7%, and 19.6%) was not significantly different across the paternal age subgroups (<35-year-old, 35-39-year-old, and ≥40-year-old, respectively; all P > 0.05), but showed a declining trend. The miscarriage rate significantly increased in the 35-39-year-old group (44.8%) compared with that in the <35-year-old group (21.0%; P < 0.05). No abnormality in newborn birth weight was found. The results indicated that paternal age over 40 years is a key risk factor that influences the assisted reproductive technology success rate even with good semen parameters, although it has no impact on embryo development., Competing Interests: None

Objective: To investigate the association between exposures to maternal affective and stress-related factors during pregnancy and allergies in children from birth to 2 years of age., Methods: We enrolled a total of 4178 children from the Shanghai Maternal-Child Pairs Cohort and measured maternal stress, anxiety, and depression during pregnancy by applying the Life Events Scale for Pregnant Women, Self-Rating Anxiety Scale, and the Center for Epidemiologic Studies-Depression Scale, respectively. Children's allergies were assessed by community physicians at 2, 6, 12, and 24 months, respectively; these included eczema, atopic dermatitis, food allergy, wheezing, asthma, and atopic rhinitis. We applied a latent class analysis (LCA) to these factors and analyzed the impacts of maternal affective and stress-related factors on childhood allergies by exploiting multivariate logistic regression., Results: Three distinct classes of children were revealed by LCA: healthy (79.8%), transient allergy (15.2%), and persistent allergy (4.9%). High maternal stress in both early and late pregnancy was associated with an increased risk of infant eczema at 2 months (aOR = 1.30, 95% CI = 1.01-1.67; aOR = 1.64, 95% CI = 1.14-2.36). Moreover, high maternal stress in late pregnancy was also associated with food allergy at 6 months, rhinitis at 2 years of age, and persistent allergy (aOR = 3.22, 95% CI = 1.27-8.12; aOR = 1.78, 95% CI = 1.01-3.15; and aOR = 1.93, 95% CI = 1.10-3.40)., Conclusions: The associations of maternal affective and stress-related factors during pregnancy with childhood allergies may vary by type and disease onset. We postulate that maternal stress in late pregnancy may exert a sustained negative effect on early childhood allergic diseases., Competing Interests: Declaration of Competing Interest The authors declare that: (i) no support, financial or otherwise, has been received from any organization that may have an interest in the submitted work; and (ii) there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Minimally invasive liver surgery (MILS) has been progressively adopted on a nationwide scale. The aim of this study is to investigate MILS implementation in a high-volume Dutch hepato-pancreato-biliary and transplant center, which is considered a moderate to low-volume center from a European standpoint., Methods: All patients who underwent MILS at Erasmus Medical Center between April 2010 and December 2021 were retrospectively reviewed. Patients' surgical outcomes were compared after stratification according to resections' difficulty and liver cirrhosis., Results: A total of 212 cases were included. Major liver resections were performed in 24 patients (11%), while minor resections were performed in 188 patients (89%). Among those, 177 (94%) resections were classified as technically minor and 11 (6%) as technically major. Major morbidity was reported in 14/177 patients (8%) after technically minor resections and in 3/24 patients (13%) after major resections. Anatomically and technically major resections had higher intraoperative blood losses (425 (0-2100) vs. 240 (50-110) vs. 100 (0-2400) mL; p-value < 0.001) and longer hospital stay (6 (3-25) vs. 5 (2-9) vs. 3 (1-44); p-value < 0.001) when compared with the technically minor counterpart. Perioperative outcomes were similar when comparing cirrhotic MILS with the non-cirrhotic cohort., Conclusion: MILS program implementation can lead to encouraging surgical outcomes even in low- to moderate-volume centers. Although low procedural volume might be predictive of impaired outcomes, long-standing experience in the HPB and liver transplant field could mitigate low-case volume effects on surgical outcomes., (© 2022. The Author(s).)

Depressive disorder is the leading cause of disability worldwide, yet the mechanisms underlying depression are not fully understood. Vesicle release is essential for synaptic neurotransmission, the abnormalities of vesicle release and synaptic plasticity are associated with various neuropsychiatric disorders. Neural circuits are ensembles of interconnected neurons that collectively perform specific functions. To some extent, depression may be caused by a disruption in the structural and functional connections of the neural circuits underlying emotion regulation. In this review, we summarized the role of abnormalities of vesicle release and synaptic transmission, as well as the related regulatory molecules and signal pathways in the regulation of depression., (Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19., Methods: This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021., Results: A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04-1.15) and parity (OR, 1.703, 95% CI, 1.13-2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns' amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2., Conclusion: At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis., Competing Interests: The authors have no potential conflicts of interest to disclosure., (© 2022 The Korean Academy of Medical Sciences.)

Background: Coronavirus disease 2019 (COVID-19) during pregnancy is associated with increased disease severity and an increased risk of perinatal complications. However, few studies of pregnant women with COVID-19 have been conducted in Korea. The purpose of this study was to describe the clinical course and pregnancy outcomes of pregnant women admitted to our hospital with COVID-19 according to the severity., Materials and Methods: This retrospective cohort study included women aged 18 years of age or older who were hospitalized in the Gachon University Gil Medical Center with COVID-19 during pregnancy between July 1, 2021 and January 31, 2022. COVID-19 severity was classified according to the "Criteria for severity classification by symptoms of COVID-19" presented by the Korea Disease Control and Prevention Agency. Severe cases were defined as those who required oxygen treatment administered via a high-flow nasal cannula or invasive mechanical ventilation or should be applied extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy., Results: A total of 103 pregnant women were hospitalized with COVID-19 during the study period. Their mean age was 33 (± 4.14) years, and 4 (3.9%) had been vaccinated against COVID-19. At the time of diagnosis of COVID-19, 3 (2.9%), 33 (32.0%), and 67 (65.1%) patients were in the first, second, and third trimester, respectively. The most common symptoms were cough (99 patients, 96.1%) and fever (85 patients, 82.5%). There was 1 (1.0%) asymptomatic patient. Forty patients (38.8%) required supplemental oxygen and 19 patients (18.4%) had severe disease. Of the 19 severe cases, 7 were in the 2nd trimester and 12 were in the 3rd trimester. Forty-one (39.8%) patients delivered, including two twin deliveries. Of the 41 cases of delivery, 14 were premature, 4 out of 21 (19.0%) in mild, 4 out of 12 (25.0%) in moderate, and 6 out of 8 (75.0%) in severe. Severe disease was associated with an increased rate of preterm birth ( P = 0.012). Four of the 43 neonates (9.1%) received oxygen treatment., Conclusion: Pregnant women with COVID-19 had a high rate of severe disease and a high preterm delivery rate, especially among those with severe disease., Competing Interests: No conflict of interest., (Copyright © 2022 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Objective: To assess the trend of incidence and survival stratified by age, race, gender and SES and the differences in time between groups in stage III-IV upper tract urothelial carcinoma (UTUC) patients., Methods: 7,505 stage III-IV UTUC patients between 2004 and 2015 were extracted from the Surveillance, Epidemiology and End Results (SEER) database. The overall survival (OS) and the cancer-specific survival (CSS) rates were assessed using the Kaplan-Meier curve and log-rank test as well as multivariate Cox regression analysis., Results: Among the 7,505 patients, 3,584 were classified as young, 2,464 were classified as middle-aged, and 1,461 were classified as elderly. The years of diagnosis were divided into three periods including 2004-2007, 2008-2011 and 2012-2015. The incidence rates for UTUC were 0.69, 0.74, and 0.77 per 100,000 in the first, second, and third period, respectively. Disparities in the long-term survival rate between male and female patients and among patients of different races narrowed over time. There was no difference in prognosis between races (p = 0.078 for OS and p = 0.167 for CSS). The difference in survival rate between the poor and rich groups narrowed along with the three time periods., Conclusions: Survival rate disparities according to sex, race, and socioeconomic status narrowed in time, except in patients aged 74-82 years. Increased age, black race, and poverty are associated with worse survival outcomes. In general, the long-term survival rate improved continuously across the three periods., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Postmeiotic spermatids use a unique strategy to coordinate gene expression with morphological transformation, in which transcription and translation take place at separate developmental stages, but how mRNAs stored as translationally inert messenger ribonucleoproteins in developing spermatids become activated remains largely unknown. Here, we report that the RNA binding protein FXR1, a member of the fragile X-related (FXR) family, is highly expressed in late spermatids and undergoes liquid-liquid phase separation (LLPS) to merge messenger ribonucleoprotein granules with the translation machinery to convert stored mRNAs into a translationally activated state. Germline-specific Fxr1 ablation in mice impaired the translation of target mRNAs and caused defective spermatid development and male infertility, and a phase separation-deficient FXR1 L351P mutation in Fxr1 knock-in mice produced the same developmental defect. These findings uncover a mechanism for translational reprogramming with LLPS as a key driver in spermiogenesis.

42Sp50 is an isoform of the eukaryotic translation elongation factor 1 A (eEF1A) and is vital for fish ovarian development. Spotted scat ( Scatophagus argus ) is a popular marine cultured fish species in Southern Asia and China, and its artificial reproduction is complicated, with a relatively low success ratio in practice. In this study, the 42Sp50 gene was cloned from spotted scat. Tissue distribution analysis showed that 42Sp50 was mainly expressed in the ovary. qRT-PCR showed that 42Sp50 expression levels gradually decreased insignificantly in the ovaries from phase II to IV. Western blot analysis showed that 42Sp50 was highly expressed in the ovary, while it was almost undetectable in the testis. Immunohistochemistry analysis stained 42Sp50 mainly in the cytoplasm of the previtellogenic oocytes in ovaries of normal XX-female and sex-reversed XY-female. Aside from fish and amphibians, 42Sp50 was also identified in some reptile species using genomic database searching. Analyses of the transcriptome data from four different fish species (Hainan medaka ( Oryzias curvinotus ), silver sillago ( Sillago sihama ), Nile tilapia ( Oreochromis niloticus ), and Hong Kong catfish ( Clarias fuscus )) revealed ovaries biased expression of 42Sp50 in all, similar to spotted scat. While the neighbor genes of 42Sp50 did not show ovary biased expression in the fish species analyzed. Bisulfite Sequencing PCR (BSP) results showed that the DNA methylation level of 42Sp50 promoter was low in ovaries, testes, and muscles. The luciferase reporter assay demonstrated that Dmrt4 activated 42Sp50 expression in the presence of Sf1 or Foxh1 . These results suggest that 42Sp50 may be involved in regulating the early phase oocytes development of spotted scat., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhi, Jiang, Mustapha, Li, Shi, Li and Zhu.)