OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

Objective To compare the efficacy and safety between thermal ablation combined with synchronous transcatheter arterial chemoembolization(TACE)and TACE in patients with liver metastasis of neuroendocrine tumors of different pathologic grades.Methods A retrospective analysis was performed on patients with liver metastases of neuroendocrine tumors admitted to Department of Interventional Radiology,Zhongshan Hospital,Fudan University from Nov 1,2006 to Jul 31,2022.The patients were divided into synchronous ablation group and TACE group according to treatment mode and subgroups according to pathological grade.The lesions were evaluated by postoperative imaging examination.The patients were followed up until Jul 31,2023,and surgery-related complications were recorded.The endpoint of prognosis were progression-free survival(PFS)and overall survival(OS).Results A total of 86 patients with neuroendocrine tumor were collected,including 34 patients in simultaneous ablation group and 52 patients in TACE group.According to WHO classification,21 patients at G1 stage,45 patients at G2 stage and 20 patients at G3 stage were included.No serious postoperative complications occurred in all patients.The median OS was 47.0(95%CI:31.2-62.8)months in the TACE group and 56.0(95%CI:8.3-73.4)months in the synchronous ablation group,with no statistical difference between the two groups(P=0.50).The median PFS was 18.0(95%CI:6.0-30.0)months in the TACE group and 29.0(95%CI:10.0-48.0)months in the synchronous ablation group,with no statistical difference between the two groups(P=0.22).Of the 45 patients at G2 stage,27 received TACE with a median OS of 47.0 months,and 18 received synchronous ablation with a median OS of 59.0 months,and there was no statistical difference between the two groups(P=0.45).The median PFS was 12.0 months in the TACE group and 32.0 months in the synchronous ablation group,and the difference between the two groups was statistically significant(P=0.03).Conclusion Comparing with TACE,simultaneous ablation can delay disease progression in patients with liver metastasis of neuroendocrine tumors to a certain extent and has good safety,especially for patients with liver metastases of neuroendocrine tumors with intermediate or low grade.

Objective: To understand the changes in pain and its effects in patients with the diagnosis of herpes zoster. Methods: A total of 3 487 patients diagnosed with herpes zoster (HZ) for the first time at the outpatient department of Miyun District Hospital from January 1, 2017, to December 31, 2019, were included in the study. The information of patients was registered and issued with a record card. Patients were required to record the time of pain and rash by themselves. Telephone follow-up was conducted at 21, 90, 180 and 365 days after the onset of rashes, including hospitalization, location of rash and pain, and the time of start and end. The impact of pain on life was evaluated by the Zoster Brief Pain Inventory (ZBPI). Results: The age of 2 999 HZ patients included in the analysis were (53±16) years old, including 1 377 (45.91%) males and 1 903 (63.45%) patients aged 50 years and older. After 21 days of rash, mild, moderate and severe pain accounted for 20.87% (626 cases), 37.98% (1 139 cases) and 33.81% (1 014 cases), respectively. Only 5.07% (152 cases) had no pain or discomfort, and 2.27% (68 cases) had no pain but discomfort. Most of the pain sites were consistent with the rash sites. The chest and back and waist and abdomen were the most common, accounting for 35.58% (1 067 cases) and 29.18% (875 cases), respectively, followed by the limbs and face and neck, accounting for 16.74% (502 cases) and 16.40% (492 cases), respectively. The M (Q₁, Q₃) of pain days in the HZ patients was 14 (8, 20) days, and the incidence of post-herpetic neuralgia (PHN) was 6.63% (171/2 580) (excluding 419 patients who refused to visit or lost to visit on 90 days after the onset of rash). The pain score of HZ patients within 21 days after the rash was (5.19±2.73) points, and the pain score of PHN patients was (7.61±2.13) points, which was significantly higher than that of non-PHN patients [(5.04±2.69) points] (P<0.001). Daily activities, emotions, walking ability, work, social interaction, sleep and recreation were affected for 21 days after the rash in HZ patients, ranging from 60.79% to 83.83%, with sleep being the most affected (83.83%). The impact scores of pain and life dimensions in PHN patients ranged from 4.59 to 7.61 points on the ZBPI scale, which were higher than those in non-PHN patients (2.49-5.04) (t values ranged from 8.86 to 11.67, all P values <0.001). Conclusion: The proportion of pain in HZ patients after the diagnosis is high, and the pain is more obvious in patients with PHN and HZ patients aged 50 and older, which has a greater impact on their daily lives.
Male ; Humans ; Middle Aged ; Aged ; Adult ; Female ; Beijing ; Follow-Up Studies ; Herpes Zoster/epidemiology* ; Pain/epidemiology* ; Exanthema

Objective: To understand the changes in pain and its effects in patients with the diagnosis of herpes zoster. Methods: A total of 3 487 patients diagnosed with herpes zoster (HZ) for the first time at the outpatient department of Miyun District Hospital from January 1, 2017, to December 31, 2019, were included in the study. The information of patients was registered and issued with a record card. Patients were required to record the time of pain and rash by themselves. Telephone follow-up was conducted at 21, 90, 180 and 365 days after the onset of rashes, including hospitalization, location of rash and pain, and the time of start and end. The impact of pain on life was evaluated by the Zoster Brief Pain Inventory (ZBPI). Results: The age of 2 999 HZ patients included in the analysis were (53±16) years old, including 1 377 (45.91%) males and 1 903 (63.45%) patients aged 50 years and older. After 21 days of rash, mild, moderate and severe pain accounted for 20.87% (626 cases), 37.98% (1 139 cases) and 33.81% (1 014 cases), respectively. Only 5.07% (152 cases) had no pain or discomfort, and 2.27% (68 cases) had no pain but discomfort. Most of the pain sites were consistent with the rash sites. The chest and back and waist and abdomen were the most common, accounting for 35.58% (1 067 cases) and 29.18% (875 cases), respectively, followed by the limbs and face and neck, accounting for 16.74% (502 cases) and 16.40% (492 cases), respectively. The M (Q₁, Q₃) of pain days in the HZ patients was 14 (8, 20) days, and the incidence of post-herpetic neuralgia (PHN) was 6.63% (171/2 580) (excluding 419 patients who refused to visit or lost to visit on 90 days after the onset of rash). The pain score of HZ patients within 21 days after the rash was (5.19±2.73) points, and the pain score of PHN patients was (7.61±2.13) points, which was significantly higher than that of non-PHN patients [(5.04±2.69) points] (P<0.001). Daily activities, emotions, walking ability, work, social interaction, sleep and recreation were affected for 21 days after the rash in HZ patients, ranging from 60.79% to 83.83%, with sleep being the most affected (83.83%). The impact scores of pain and life dimensions in PHN patients ranged from 4.59 to 7.61 points on the ZBPI scale, which were higher than those in non-PHN patients (2.49-5.04) (t values ranged from 8.86 to 11.67, all P values <0.001). Conclusion: The proportion of pain in HZ patients after the diagnosis is high, and the pain is more obvious in patients with PHN and HZ patients aged 50 and older, which has a greater impact on their daily lives.
Male ; Humans ; Middle Aged ; Aged ; Adult ; Female ; Beijing ; Follow-Up Studies ; Herpes Zoster/epidemiology* ; Pain/epidemiology* ; Exanthema

Bivalves are species-rich mollusks with prominent protective roles in coastal ecosystems.Across these ancient lineages,colony-founding larvae anchor themselves either by byssus produc-tion or by cemented attachment.The latter mode of sessile life is strongly molded by left-right shell asymmetry during larval development of Ostreoida oysters such as Crassostrea hongkongensis.Here,we sequenced the genome of C.hongkongensis in high resolution and compared it to reference bivalve genomes to unveil genomic determinants driving cemented attachment and shell asymmetry.Importantly,loss of the homeobox gene Antennapedia(Antp)and broad expansion of lineage-specific extracellular gene families are implicated in a shift from byssal to cemented attachment in bivalves.Comparative transcriptomic analysis shows a conspicuous divergence between left-right asymmetrical C.hongkongensis and symmetrical Pinctada fucata in their expression profiles.Especially,a couple of orthologous transcription factor genes and lineage-specific shell-related gene families including that encoding tyrosinases are elevated,and may cooperatively govern asymmet-rical shell formation in Ostreoida oysters.

Ovarian cancer is one of the three most common gynecological cancers in the world, and is regarded as a priority in terms of women's cancer. In the past few years, many researchers have attempted to develop and apply artificial intelligence (AI) techniques to multiple clinical scenarios of ovarian cancer, especially in the field of medical imaging. AI-assisted imaging studies have involved computer tomography (CT), ultrasonography (US), and magnetic resonance imaging (MRI). In this review, we perform a literature search on the published studies that using AI techniques in the medical care of ovarian cancer, and bring up the advances in terms of four clinical aspects, including medical diagnosis, pathological classification, targeted biopsy guidance, and prognosis prediction. Meanwhile, current status and existing issues of the researches on AI application in ovarian cancer are discussed.
Artificial Intelligence ; Female ; Humans ; Magnetic Resonance Imaging ; Ovarian Neoplasms/diagnostic imaging* ; Prognosis ; Tomography, X-Ray Computed

Objective We developed a universal lesion detector (ULDor) which showed good performance in in-lab experiments. The study aims to evaluate the performance and its ability to generalize in clinical setting via both external and internal validation. Methods The ULDor system consists of a convolutional neural network (CNN) trained on around 80K lesion annotations from about 12K CT studies in the DeepLesion dataset and 5 other public organ-specific datasets. During the validation process, the test sets include two parts: the external validation dataset which was comprised of 164 sets of non-contrasted chest and upper abdomen CT scans from a comprehensive hospital, and the internal validation dataset which was comprised of 187 sets of low-dose helical CT scans from the National Lung Screening Trial (NLST). We ran the model on the two test sets to output lesion detection. Three board-certified radiologists read the CT scans and verified the detection results of ULDor. We used positive predictive value (PPV) and sensitivity to evaluate the performance of the model in detecting space-occupying lesions at all extra-pulmonary organs visualized on CT images, including liver, kidney, pancreas, adrenal, spleen, esophagus, thyroid, lymph nodes, body wall, thoracic spine,
Computer Simulation ; Computers ; Neural Networks, Computer ; Tomography, X-Ray Computed

In mammals, the gonad is composed of germ cells and somatic cells. The gonads have the potential of bidirectional differentiation before sex determination. The differentiation of somatic cells in the gonad determines the development of testis or ovary, and this process is regulated by many factors. SRY, SOX9, SOX3, SOX8, SOX10, FGF9/FGFR2, PGD2, AMH, and DMRT1 are involved in the differentiation of testis. By contrast, FOXL2, CTNNB1, RSPO1, WNT4, Follistatin, ERα/β, and BMP2 play important roles in ovary development. If these molecular regulatory networks are damaged by endogenous or exogenous factors, disorders of sex differentiation, even sex reversal, will occur. In this review, the regulation of somatic cell fate during gonad primordium formation and sex determination in mouse model was discussed.

As a member of the nuclear receptor superfamily, the pregnane X receptor (PXR) is a ligand-activated transcription factor. PXR is highly expressed in liver and intestinal tissues, and also found in other tissues and organs, such as stomach and kidney. After heterodimerization with retinoid X receptor (RXR), PXR recruits numerous co-activating factors, and binds to specific DNA response elements to perform transcriptional regulation of the downstream target genes. As an acknowledged receptor for xenobiotics, PXR was initially considered as a nuclear receptor regulating drug metabolizing enzymes and transporters. However, nowadays, PXR has also been recognized as an important endobiotic receptor. Recent studies have shown that PXR activation can regulate glucose metabolism, lipid metabolism, steroid endocrine homeostasis, detoxification of cholic acid and bilirubin, bone mineral balance, and immune inflammation in vivo. This review focuses on the role of PXR in metabolism of endogenous substances.
Animals ; Gene Expression Regulation ; Humans ; Pregnane X Receptor ; metabolism ; Xenobiotics ; metabolism

OBJECTIVE: To investigate the effect of transurethral resection of bladder neck on primary female bladder neck obstruction and to analyze the expression of three kinds of sex hormone receptor (SR) in female bladder neck tissues diagnosed as primary bladder neck obstruction by the immunochemistry and statistics. METHODS: The clinical data of 40 female patients, admitted into Peking University People's Hospital for difficulty of voiding during Oct.2008 and Dec.2013 and eventually diagnosed as bladder outlet obstruction (BOO) by urodynamics, were retrospectively reviewed. BOO was defined as a maximum flow rate (Q_max) less than 12 mL/s together with a detrusor pressure at maximum flow rate (Pdet Q_max) more than 25 cmH₂O in urodynamic study in the absence of neurological disorders. Diagnosis was confirmed by the cystoscopy. Preoperative and postoperative AUASS scores were recorded and analyzed for observation of curative effects and complications. The immunochemical expression of SR of primary female bladder neck obstruction (PBNO) tissues and normal control was examined and applied to statistical analysis. RESULTS: There were significant changes postoperatively in voiding scores, storage scores and total scores (P<0.001). Postoperatively, 1 patient newly presented with overactive bladder (OAB), 4 patients newly presented with hematuria, and 1 patient underwent cystostomy. The symptoms of urinary retention with overflow incontinence in 2 patients disappeared after the surgery, and 3 patients complicated with OAB complained without urgency. In addition, pre-hydronephrosis improved postoperatively in six patients. The subjective satisfactory rate to the surgery of TURBN was 77.5% (31/40). Sex hormone receptor, including androgen receptor (AR), estrogen receptor (ER), progesterone receptor (PR), expressed in both bladder neck tissues of normal control and PBNO patients. In PBNO group, the expression of PR was significantly lower than that of control group (P<0.05), while the other 2 SRs expressed with no significantly statistical difference. PBNO patients were divided into 2 groups, according to their symptoms scores, and the expression of SRs showed no significant differences among the mild, moderate and severe groups (P>0.05). CONCLUSION The transurethral bladder neck resection is valid in treating with female PBNO patients, with rarely occurrence of complications. PR expressed less in the female bladder neck tissues, and is possibly correlated with the occurrence of female PBNO.
Female ; Humans ; Retrospective Studies ; Urinary Bladder Neck Obstruction/surgery* ; Urodynamics