Anxiety disorder is a highly prevalent psychological illness, and research has shown that obesity is a significant risk factor for its development. This study explored the ameliorative effects and mechanisms of saponins from Panax japonicus(SPJ) on anxiety disorder in mice fed a high-fat diet(HFD). Fifty C57BL/6J mice were randomly divided into normal control diet(NCD) group, HFD group, and low-and high-dose SPJ groups. At week 12, six mice from the HFD group were further divided into a control group(treated with DMSO) and an exogenous fibroblast growth factor 21(FGF21) group(administered rFGF21). The anxiety-like behavior of the mice was assessed using the open field test and elevated plus maze test. Hematoxylin-eosin(HE) staining and oil red O staining were performed to observe pathological changes in the liver and adipose tissue. Glucose metabolism was evaluated through the glucose tolerance test(GTT) and insulin tolerance test(ITT). Western blot analysis was performed to detect the expression of FGF21 and its downstream-related proteins in the liver and cortex, along with the expression of brain-derived neurotrophic factor(BDNF), disks large homolog 4(DLG4), and synaptophysin(SYP) in the cortex. Real-time quantitative fluorescent PCR(qPCR) was used to detect the expression of FGF21 and its receptor genes in the liver and cortex. Immunofluorescence staining was employed to examine the expression of neuronal activator c-Fos, FGF21, and the FGF21 co-receptor β-klotho in the cerebral cortex. The results showed that SPJ significantly improved the frequency of activity in the open arms of the elevated plus maze and the central area of the open field in HFD mice, up-regulated the expression of BDNF, DLG4, and SYP, and effectively alleviated anxiety-like behaviors in HFD mice. Compared with the NCD group, HFD mice exhibited up-regulated expression of FGF21 in the liver and cerebral cortex, while the expression of fibroblast growth factor receptor 1(FGFR1) and β-klotho was significantly down-regulated, suggesting that HFD mice exhibited FGF21 resistance. SPJ markedly up-regulated the β-klotho levels in HFD mice, reversing FGF21 resistance. Further comparison with exogenously administered FGF21 revealed that SPJ activates brain cortical regions in a consistent manner, and additionally, SPJ promotes the number and colocalization of c-Fos and β-klotho positive cells in the brain cortex. In summary, SPJ effectively alleviates anxiety-like behaviors in HFD mice. Its mechanism is associated with up-regulation of β-klotho expression in the brain, reversal of FGF21 resistance, and subsequent activation of neurons in the cerebral cortex and amygdala.
Animals ; Diet, High-Fat/adverse effects* ; Fibroblast Growth Factors/genetics* ; Mice ; Male ; Panax/chemistry* ; Mice, Inbred C57BL ; Anxiety/etiology* ; Saponins/administration & dosage* ; Brain-Derived Neurotrophic Factor/genetics* ; Humans ; Liver/metabolism* ; Drugs, Chinese Herbal/administration & dosage*

OBJECTIVE: To investigate lymph node metastasis (LNM) in the prostatic anterior fat pad (PAFP) of PCa patients after robot-assisted radical prostatectomy (RARP), and analyze the clinicopathological features and prognosis of LNM in the PAFP. METHODS: We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urology of PLA General Hospital from January 2017 to December 2022. All the patients underwent routine removal of the PAFP during RARP and pathological examination, with the results of all the specimens examined and reported by pathologists. Based on the presence and locations of LNM, we grouped the patients for statistical analysis, compared the clinicopathological features between different groups using the Student's t, Mann-Whitney U and Chi-square tests, and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio. RESULTS: Lymph nodes were detected in 77 (7.7%) of the 1 003 PAFP samples, and LNM in 11 (14.3%) of the 77 cases, with a positive rate of 1.1% (11/1 003). Of the 11 positive cases, 9 were found in the upgraded pathological N stage, and the other 2 complicated by pelvic LNM. The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group (81.8% ［9/11］ vs 36.2% ［359/992］, P = 0.005), and so did the cases with Gleason score ≥8 (87.5% ［7/8］ vs 35.5% ［279/786］, P = 0.009). No statistically significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the patients with PAFP LNM only and those with pelvic LNM only. CONCLUSION The PAFP is a potential route to LNM, and patients with LNM in the PAFP are characterized by poor pathological features. There is no statistically significant difference in biochemical recurrence-free survival between the patients with PAFP LNM only and those with pelvic LNM only. Routine removal of the PAFP and independent pathological examination of the specimen during RARP is of great clinical significance.
Humans ; Male ; Prostatectomy/methods* ; Robotic Surgical Procedures ; Lymphatic Metastasis ; Retrospective Studies ; Prognosis ; Prostatic Neoplasms/pathology* ; Adipose Tissue/pathology* ; Prostate/pathology* ; Lymph Nodes/pathology* ; Middle Aged ; Aged

BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

Japanese spotted fever(JSF)is an infectious disease caused by Rickettsia japonica,with nonspecific clinical symptoms and a high risk of misdiagnosis.We reported a case of JSF,in which Rickettsia japonica was detected in blood cells by metagenomic next-generation sequencing.The patient recovered after treatment with doxycycline.This report provides a reference for the clinical diagnosis and treatment of JSF.
Humans ; High-Throughput Nucleotide Sequencing ; Metagenomics ; Rickettsia/isolation & purification* ; Spotted Fever Group Rickettsiosis/microbiology*

Objective:To explore the application effect of microsurgical thinning optimized anterolateral thigh flap in the repair of limb tumor wounds.Methods:A retrospective analysis was conducted on the clinical data of patients with limb tumors at the Microsurgery and Reconstruction Department of Xuzhou Renci Hospital from January 2019 to January 2021. All patients underwent surgical resection of the lesions and were repaired with microsurgical thinning optimized anterolateral thigh flap. The outpatient follow-up was conducted after surgery. One year after surgery, limb function and appearance were evaluated using the Musculoskeletal Tumor Society (MSTS) bone tumor limb salvage surgery limb energy scale and efficacy satisfaction score. The total score is 30 points, and a higher score indicates better function. The limb appearance was evaluated using a satisfaction score scale, with a total score of 5-10 points being satisfactory, 0-4 points being average, and -5 to -1 points considered unsatisfactory. Descriptive methods were used for statistical analysis, and normally distributed measurement data were expressed as Mean±SD.Results:A total of 11 patients were included, comprising 7 males and 4 females, aged between 19 and 55 years, with an average age of 31.5 years. Among them, there were 3 cases of dermatofibrosarcoma protuberans, 4 cases of invasive fibroma, 1 case of mucinous fibrosarcoma, 2 cases of malignant fibrous histiocytoma, and 1 case of squamous cell carcinoma of the skin. The tumor lesion ranged from 5.5 cm × 8.0 cm to 9.0 cm × 19.0 cm, and the tumor resection range during surgery was from 6.5 cm × 9.0 cm to 10.0 cm × 20.0 cm. The size of the skin flap ranged from 7.5 cm × 11.0 cm to 10.0 cm × 22.5 cm. The average thickness of the flap before thinning was 2.2 cm (1.6-3.5 cm), and the average thickness after thinning was 1.2 cm (0.9-1.7 cm). One case of superficial necrosis occurred at the edge of the flap measuring 1.5 cm × 2.0 cm after surgery, and the wound healed after dressing changes. One case of arterial crisis occurred 48 hours after surgery, and thrombus formation was detected at the distal end of the anastomosis during exploration. After reanastomosis, blood flow was restored. The remaining flaps survived well, and the incisions healed in one stage. The average postoperative follow-up period was 14.5 months (12-18 months) with no tumor recurrence. The MSTS score for limb function was (25.2±2.1) points, and the satisfaction score for limb appearance efficacy was (7.4±1.6) points, with a satisfaction rate of 10 out of 11.Conclusion:The application of microsurgical thinning optimized anterolateral thigh flap in the plastic surgery of limb tumors can restore satisfactory limb function and appearance, making it an ideal surgical method.

Objective:To explore the application effect of microsurgical thinning optimized anterolateral thigh flap in the repair of limb tumor wounds.Methods:A retrospective analysis was conducted on the clinical data of patients with limb tumors at the Microsurgery and Reconstruction Department of Xuzhou Renci Hospital from January 2019 to January 2021. All patients underwent surgical resection of the lesions and were repaired with microsurgical thinning optimized anterolateral thigh flap. The outpatient follow-up was conducted after surgery. One year after surgery, limb function and appearance were evaluated using the Musculoskeletal Tumor Society (MSTS) bone tumor limb salvage surgery limb energy scale and efficacy satisfaction score. The total score is 30 points, and a higher score indicates better function. The limb appearance was evaluated using a satisfaction score scale, with a total score of 5-10 points being satisfactory, 0-4 points being average, and -5 to -1 points considered unsatisfactory. Descriptive methods were used for statistical analysis, and normally distributed measurement data were expressed as Mean±SD.Results:A total of 11 patients were included, comprising 7 males and 4 females, aged between 19 and 55 years, with an average age of 31.5 years. Among them, there were 3 cases of dermatofibrosarcoma protuberans, 4 cases of invasive fibroma, 1 case of mucinous fibrosarcoma, 2 cases of malignant fibrous histiocytoma, and 1 case of squamous cell carcinoma of the skin. The tumor lesion ranged from 5.5 cm × 8.0 cm to 9.0 cm × 19.0 cm, and the tumor resection range during surgery was from 6.5 cm × 9.0 cm to 10.0 cm × 20.0 cm. The size of the skin flap ranged from 7.5 cm × 11.0 cm to 10.0 cm × 22.5 cm. The average thickness of the flap before thinning was 2.2 cm (1.6-3.5 cm), and the average thickness after thinning was 1.2 cm (0.9-1.7 cm). One case of superficial necrosis occurred at the edge of the flap measuring 1.5 cm × 2.0 cm after surgery, and the wound healed after dressing changes. One case of arterial crisis occurred 48 hours after surgery, and thrombus formation was detected at the distal end of the anastomosis during exploration. After reanastomosis, blood flow was restored. The remaining flaps survived well, and the incisions healed in one stage. The average postoperative follow-up period was 14.5 months (12-18 months) with no tumor recurrence. The MSTS score for limb function was (25.2±2.1) points, and the satisfaction score for limb appearance efficacy was (7.4±1.6) points, with a satisfaction rate of 10 out of 11.Conclusion:The application of microsurgical thinning optimized anterolateral thigh flap in the plastic surgery of limb tumors can restore satisfactory limb function and appearance, making it an ideal surgical method.

Objective:To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR.Methods:A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m 2 day 1, cisplatin 25 mg/m 2 days 1-3, and capecitabine 800 mg/m 2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results:A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm 3. The T stage ( OR=12.71, 95% CI: 1.4-112.5, P=0.022) and the volume ( OR=7.1, 95% CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion:The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.