BackgroundBoth modified Suanzaoren Decoction and estazolam serve as effective treatments for chronic insomnia disorder （CID）. Default mode network （DMN） dysfunction is recognized as the primary pathophysiological mechanism underlying CID. However， it remains unclear whether the two treatments exert their therapeutic effects via convergent modulation of DMN functional connectivity. ObjectiveTo investigate the convergent remodeling characteristics of bidirectional effective connectivity （EC） of core DMN nodes with both the intra-network and the remaining whole-brain regions in CID patients with Yin-deficiency and fire-hyperactivity syndrome following the treatment with modified Suanzaoren Decoction or estazolam， so as to provide neuroimaging evidence for the convergent neural mechanisms underlying the therapeutic effects of both therapies in treating CID. MethodsEighty-two patients diagnosed with CID according to the International Classification of Sleep Disorder， third edition （ICSD-3） were consecutively recruited from the outpatient clinic of the Inner Mongolia Autonomous Region Mental Health Center from October 2020 to September 2023. Based on treatment preference， patients were assigned to receive a 6-week intervention in either the modified Suanzaoren Decoction group （n=52） or the estazolam group （n=30）. Ultimately， 66 patients completed follow-up assessments （modified Suanzaoren Decoction group， n=41； estazolam group， n=25）. All CID patients underwent resting-state functional magnetic resonance imaging scanning before and after treatment. Core DMN nodes including medial prefrontal cortex （mPFC）， bilateral inferior parietal lobule （IPL）， and precuneus （PCUN） were selected as seed regions. Granger causality analysis （GCA） was employed to assess bidirectional EC between the seed regions and both the other intra-DMN nodes and the remaining whole-brain regions. Hepatic and renal function indices were detected pre- and post-treatment to evaluate the safety profiles of both treatments. ResultsAt baseline， significant between-group differences were identified in EC from the left IPL to the left middle fronto-orbital gyrus/gyrus rectus （t=5.24， Z=4.84， voxel-level P<0.001， cluster-level P<0.05， GRF-corrected）， with the modified Suanzaoren Decoction group exhibiting stronger EC than the estazolam group. No significant between-group differences were observed in EC between other core DMN nodes and remaining whole-brain regions （P>0.05）. Within-group pre- to post-treatment comparisons demonstrated consistent connectivity alterations in both groups. Specifically， EC from the left IPL to the supplementary motor area （SMA） decreased after treatment （modified Suanzaoren Decoction group： t=-6.28， Z=5.208； estazolam group： t=-5.58， Z=4.425）. Conversely， EC from the SMA to the left IPL increased （modified Suanzaoren Decoction group： t=5.89， Z=4.968； estazolam group： t=6.15， Z=4.720）. Furthermore， both groups demonstrated reduced EC from the PCUN to the left IPL （modified Suanzaoren Decoction group： t=-5.85， Z=4.94； estazolam group： t=-5.75， Z=4.515）， and elevated EC from the left IPL to the PCUN （modified Suanzaoren Decoction group： t=5.29， Z=4.579； estazolam group： t=4.55， Z=3.826） （voxel-level P<0.001， cluster-level P<0.05， GRF-corrected）. No significant pre- to post-treatment differences were observed in hepatic or renal function indices in either group （P>0.05）. ConclusionIn CID patients with Yin-deficiency and fire-hyperactivity syndrome， both modified Suanzaoren Decoction and estazolam induce convergent bidirectional remodeling of EC between the left IPL and the SMA and the PCUN. ［Funded by Natural Science Fund Project of Inner Mongolia Autonomous Region （number， 2019MS08099）； ClinicalTrials.gov number， NCT06452953］

OBJECTIVE Aimed to investigate the impact of comorbid asthma on chronic rhinosinusitis with nasal polyps(CRSwNP)and identify key proteins and signaling pathways.METHODS Proteomic methods were employed to analyze differentially expressed proteins(DEPs)in nasal lavage fluid(NLF)from control,CRSwNP,and CRSwNP with asthma groups.DIA quantitative analysis technology was used to assess the gradient changes of DEPs among the three groups to determine key proteins affected by comorbid asthma in CRSwNP.RESULTS Compared to the control group,1 377 and 1 006 DEPs were identified in the CRSwNP and CRSwNP with asthma groups,respectively.Peroxiredoxin-5(PRDX5),Ran-Binding Protein 1(RanBP1)(upregulated),and Keratin 9(KRT9)(downregulated)were identified as key proteins affecting CRSwNP with asthma.CONCLUSION Comorbid asthma may promote the occurrence and development of nasal polyps through specific key proteins and signaling pathways,providing new molecular insights into the interaction between CRSwNP and asthma.

Objective:To investigate the impact of tumor origin (ventral pancreatic origin and dorsal pancreatic origin) on prognosis in patients with pancreatic head cancer.Methods:A retrospective analysis was performed on the clinical data of 150 patients with pancreatic head cancer who received surgical treatment at the First Affiliated Hospital of the Naval Medical University from October 2014 to December 2017. Among these patients, 92 were male and 58 were female, aged (61.2±8.8) years. The 150 patients were divided into two groups based on tumor origin: the ventral pancreatic cancer group ( n=72) and the dorsal pancreatic cancer group ( n=78). A comparative analysis of clinical, pathological, and imaging charac-teristics was conducted between the two groups. Univariate and multivariable Cox proportional hazards models were used to analyze the association between pancreatic head cancer origin and overall survival (OS). Results:Patients with pancreatic head carcinoma arising from the ventral and dorsal pancreas accounted for 48%(72/150) and 52%(78/150) of the study cohort, respectively. Pancreatic head carcinoma arising from the dorsal pancreas were more likely to show pathological features of pancreatic parenchymal atrophy [73.1%(57/78) vs. 47.2%(34/72), χ2=10.49, P=0.001] and pancreatitis [44.9%(35/78) vs. 29.2%(21/72), χ2=3.95, P=0.047]. In contrast, patients with pancreatic head carcinoma arising from the ventral pancreas was more frequently associated with contact with the superior mesenteric artery [25.0%(18/72) vs. 1.3%(1/78), χ2=19.04, P<0.001], perineural invasion [100%(72/72) vs. 88.5%(69/78), χ2=8.84, P=0.003], and positive surgical margins [15.3%(11/72) vs. 2.6%(2/78), χ2=7.65, P=0.006], with all differences statistically significant. The ventral pancreatic cancer group demonstrated cumulative survival rates of 33.2% and 0 at 1-year and 2-year postoperative intervals, respectively, while the dorsal pancreatic cancer group exhibited rates of 56.7% and 24.8% at the corresponding timepoints. Comparison of Kaplan-Meier survival curves between the two groups showed a statistically significant difference ( χ2=6.00, P=0.014). Multivariable Cox proportional hazards analysis identified dorsal pancreatic origin pancreatic head cancer as an independent predictor of increased mortality risk compared to ventral origin tumors ( HR=2.75, 95% CI: 1.52-4.98, P=0.001). Conclusion:The embryonic origin of pancreatic head cancer determines its clinical, pathological, and imaging heterogeneity, and pancreatic head cancer arising from the ventral pancreas demonstrates significantly worse prognostic outcomes compared to dorsal pancreatic origin.

Objective To explore the promoting effect of long-term administration of nicotiflorin on the recovery of neurological function in rats with cerebral ischemia-reperfusion injury （CIRI）. Methods The CIRI model was established and nicotiflorin was injected intraperitoneally after 1 hour of obstruction for 8 weeks. Tail suspension deflection experiment, balance beam experiment and water maze test were performed in the 2nd, 4th and 8th weeks. After 8 weeks, TTC staining was used to observe the volume of infarct atrophy, transcriptome sequencing was employed to screen differential expressed genes （DEGs） and highly enriched pathways were analyzed, Western-bloting and Elisa were used to assess proteins expression related to the pyroptosis pathway and inflammatory cytokines IL-1β and IL-18. Results By long-term administration of nicotiflorin, the contralateral deflection rate was significantly reduced and beam experiment score of CIRI rats was balanced, the number of crossing the platform in water maze test was increased （P<0.05）, the volume of cerebral infarction atrophy was decreased （P<0.01）, which significantly promoted the recovery of neurological function in rats. Transcriptome sequencing found that the expression of genes in the pyroptosis-related signaling pathways in the brain tissue of rats in the nicotiflorin group was significantly down-regulated （P<0.05）. Western-blot and Elisa experiments showed that nicotiflorin reduced the expression levels of Caspase-1 and GSDMD-N and other pyroptosis-related proteins, and at the same time, the release of inflammatory factors IL-1β and IL-18 was significantly reduced （P<0.05）, indicating that nicotiflorin could inhibit the inflammatory process of pyroptosis. Conclusion Nicotiflorin exhibited a significant long-term promotion effect on the recovery of neurological function in CIRI rats, which potentially attributed from its ability to inhibit pyroptosis.

Objective:To investigate the predictive value of anti-Müllerian hormone (AMH) on the outcome of microscopic testicular sperm extraction (micro-TESE) in patients with non-mosaic Klinefelter syndrome (KS) of the clinical data and to identify effective predictors for successful micro-TESE.Methods:A retrospective case-control study was conducted on the clinical data of 118 non-mosaic KS patients treated at the Center for Reproductive Medicine of the First Affiliated Hospital of Zhengzhou University between May 2018 and September 2023. Patients were divided into two groups based on whether sperm were successfully retrieved via micro-TESE: the sperm retrieved group ( n=45) and the no sperm retrieved group ( n=73). Differences between the two groups were compared, and multivariate logistic regression analysis was used to identify factors influencing sperm retrieval. Changes in testicular volume and sex hormone levels before and after surgery were also assessed. Results:The sperm retrieval rate was 38.1% (45/118). Patients in the sperm retrieved group were significantly younger [(26.93±3.80) years] than those in the no sperm retrieved group [(28.27±3.92) years, P=0.029], and the AMH level was significantly higher [0.44 (0.18, 1.13) μg/L] than that in the no sperm retrieved group [0.10 (0.03, 0.22) μg/L, P<0.001]. AMH was identified as an independent predictor of micro-TESE outcome in non-mosaic KS patients ( OR=7.867, 95% CI: 2.727-27.242, P=0.001). The area under the receiver operating characteristic curve was 0.802 (95% CI: 0.722-0.883), and the optimal reference threshold for AMH was ≥0.265 μg/L. Postoperatively, testosterone levels decreased significantly by a median of 0.27 μg/L ( P=0.019), while luteinizing hormone levels increased by a median of 2.08 U/L ( P=0.049), with a more significant decline in testosterone levels observed in the no sperm retrieved group by a median of 0.29 μg/L ( P=0.022). Conclusion:AMH can predict successful micro-TESE in non-mosaic KS patients, with higher AMH levels indicating a higher likelihood of success.

Objective To develop and validate a model to predict the risk of radiation-induced lung injury (RILI) and assess its clinical feasibility. Methods Clinical data from 125 patients with non-small cell lung cancer (NSCLC) were included in the study. The patients were divided into training group (88 cases) and validation group (38 cases). Key predictive factors were identified using univariate and multivariate logistic regression analyses combined with least absolute shrinkage and selection operator (LASSO) regression. A predictive model was constructed and evaluated using a nomogram, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. Results The key variables identified by the model were tumor volume (P = 0.017), Eastern Cooperative Oncology Group performance status score (P = 0.035), 95% of the minimum dose to the target volume (P = 0.028), percentage of bilateral lung volume receiving 20 Gy of radiation (P < 0.001), and neutrophil-to-lymphocyte ratio (P = 0.021). The ROC curve showed that the areas under the curve (AUC) for the model in the training and validation groups were 0.987 and 0.992, respectively, indicating good predictive ability. The calibration curve and decision curve further confirmed the accuracy and clinical practicability of the model. Conclusion The predictive model proposed in this study can accurately assess the risk of developing RILI in patients with NSCLC who have undergone radiotherapy, demonstrating its potential value in clinical practice.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective:To investigate the predictive value of anti-Müllerian hormone (AMH) on the outcome of microscopic testicular sperm extraction (micro-TESE) in patients with non-mosaic Klinefelter syndrome (KS) of the clinical data and to identify effective predictors for successful micro-TESE.Methods:A retrospective case-control study was conducted on the clinical data of 118 non-mosaic KS patients treated at the Center for Reproductive Medicine of the First Affiliated Hospital of Zhengzhou University between May 2018 and September 2023. Patients were divided into two groups based on whether sperm were successfully retrieved via micro-TESE: the sperm retrieved group ( n=45) and the no sperm retrieved group ( n=73). Differences between the two groups were compared, and multivariate logistic regression analysis was used to identify factors influencing sperm retrieval. Changes in testicular volume and sex hormone levels before and after surgery were also assessed. Results:The sperm retrieval rate was 38.1% (45/118). Patients in the sperm retrieved group were significantly younger [(26.93±3.80) years] than those in the no sperm retrieved group [(28.27±3.92) years, P=0.029], and the AMH level was significantly higher [0.44 (0.18, 1.13) μg/L] than that in the no sperm retrieved group [0.10 (0.03, 0.22) μg/L, P<0.001]. AMH was identified as an independent predictor of micro-TESE outcome in non-mosaic KS patients ( OR=7.867, 95% CI: 2.727-27.242, P=0.001). The area under the receiver operating characteristic curve was 0.802 (95% CI: 0.722-0.883), and the optimal reference threshold for AMH was ≥0.265 μg/L. Postoperatively, testosterone levels decreased significantly by a median of 0.27 μg/L ( P=0.019), while luteinizing hormone levels increased by a median of 2.08 U/L ( P=0.049), with a more significant decline in testosterone levels observed in the no sperm retrieved group by a median of 0.29 μg/L ( P=0.022). Conclusion:AMH can predict successful micro-TESE in non-mosaic KS patients, with higher AMH levels indicating a higher likelihood of success.

The diagnostic value of Mycobacterium tuberculosis(MTB)complex and rifampicin resistance test kits(fluorescence PCR method)in detecting for MTB complex and rifampicin resistancein sputum samples was evaluated.A total of 271 patients with suspected tuberculosis were prospectively and consecutively enrolled at Hunan Chest Hospital between April 1,2024,and November 30,2024.Of these,229 patients were confirmed to have tuberculosis,whereas 42 patients were not-tuberculosis samples were col-lected from all patients and subjected to fluorescence PCR,Xpert MTB/RIF(abbreviated as Xpert),and MGIT 960 culture and drug sensitivity testing.Clinical diagnosis and MTB culture results served as reference standards for TB diagnosis,whereas phenotypic drug susceptibility testing and Xpert served as reference standards to for assessment of rifampicin resistance.The sensitivity,specificity,positive predictive value,and negative predictive value of the fluorescence PCR method were analyzed.Kappa tests were performed to analyze the concordance between detection techniques.With clinical diagnosis as the gold standard,the sensitivity and specificity of the fluorescence PCR method for the diagnosis of TB were 65.1%(149/229)and 97.6%(41/42),and the consistency test for the fluo-rescence PCR and Xpert methods showed high consistency(Kappa value=0.993).With the MGIT 960 liquid culture as the reference standard,the positive detection rate of the fluorescence PCR method for the detection of patients with positive cultures was 91.9%(102/111,95%CI:85.2%-96.2%),and the positive detection rate for 147 patients with sputum culture-negative TB was 27.9%(41/147,95%CI:21.3%-35.6%).With the phenotypic drug sensitivity test as the gold standard,the sensitivity and specificity of the fluo-rescence PCR method for the detection of rifampicin resistance were 100.0%(31/31)and 96.6%(28/29)respectively,and the consis-tency between tests was high(Kappa value=0.967).With Xpert as the gold standard,the sensitivity and specificity of fluorescence PCR for the detection of rifampicin resistance were 95.8%(46/48)and 99.0%(99/100),respectively,and the consistency between tests was high(Kappa value=0.953).Finally,samples with rifampicin resistance detected with the fluorescence PCR method had a clear rpoB gene mutation type according to one-generation sequencing.In conclusion,the fluorescence PCR method showed high sen-sitivity in detecting MTB complex groups and rifampicin resistance,and had high concordance with Xpert.Therefore,this technique can serve a rapid test for TB diagnosis to increase the rate of positive TB pathology and detection of rifampicin resistance.This method is particularly suitable for use in lower-income countries and economically disadvantaged grassroots communities.

OBJECTIVE To establish skin contamination models with sulfur mustard analogue 1-chloro-2-ethylsulfanyl ethane(CEES),and evaluate the therapeutic efficacy of reactive skin decontamination lotion kit(RSDL).METHODS ①Kunming,BALB/c,BALB/c-nu,and C57BL/6N were contaminted with CEES 75 μL·kg-1 using exposed method and covered method for 10 min on the dorsal skin.Wound healing times and areas were assessed to determine the stock of mice and exposure method.② BALB/c mice were exposed to a gradient of CEES at the doses of 75,150,250,350 and 500 μL·kg-1(10 min)using the covered method.Wound healing times,areas and Kaplan-Meier survival curves were used to determine the optimal dose.③ BALB/c mice were exposed to CEES 150 μL·kg-1 for varying durations(5,10 and 20 min)using the covered method.Wound healing times,areas and Kaplan-Meier survival curves were analyzed to determine the optimal exposure time.④ BALB/c mice were divided into four groups:control(exposed with the covered method at 150 μL·kg-1,10 min),treatment(20 μL RSDL treatment after exposure,as the control group),5 min treatment(20 μL RSDL treatment after 5 min of exposure,followed by 5 min of coverage)and immediate-treatment(exposed with the exposed method at 150 μL·kg-1,immediately treated with 20 μL RSDL,followed by 10 min of coverage).The therapeutic efficacy was evaluated based on the wound area,subcutaneous microvesicle count,epidermal thick-ness,and inflammatory cytokine(IL-6 and TNF-α)expressions.RESULTS ① The covered method caused more severe and prolonged wounds than the exposed method.BALB/c mice exhibited a high sensitivity to CEES with delayed wound healing and were therefore selected as the model animal.② Survival rates in BALB/c mice dropped below 50%at doses of 250,350 and 500 μL·kg-1,whereas an 83.3%survival rate was observed at 150 μL·kg-1.③ The mice exposed to CEES(150 μL·kg-1,20 min)died within 3 days.The wound area was consistently smaller in the 5 min covered group than in the 10 min covered group.④CEES-induced skin injury led to epidermal nuclear pyknosis,follicular disrup-tion,inflammatory infiltration,and microvesicle formation in both treatment and poisoned control groups.As more immediate treatment,the wound area significantly decreased.While the IL-6 expres-sion showed no significant intergroup difference,the TNF-α expression was significantly higher in the treatment group.CONCLUSION A CEES-induced skin contamination model has been established in BALB/c mice using the covered method(150 μL·kg-1,10 min covered).However,RSDL should be ad-ministered in 10 min post-contamination.