Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Liver cancer is one of the most common cancers,and its common surgical treatment methods include tran-scatheter arterial chemoembolization,radiofrequency ablation,and liver transplantation surgery.However,the treatment effect of these surgeries on patients with mid-to late-stage liver cancer is not ideal.In recent years,with the continuous development of tumor gene therapy and tumor immunology,tumor treatment methods have transitioned from traditional models to targeted onco-lytic virus therapy.With the advantages of fast replication,the oncolytic virus can kill tumor cells without damaging other normal cells and realize the targeted treatment of liver cancer through mechanisms such as activating the immune system and improving the tumor microenvironment.In addition,immunotherapy can reduce tumor recurrence and metastasis,thereby exerting therapeutic effects on liver cancer.This article reviews the research progress of oncolytic virus and immunotherapy for liver cancer,aiming to provide a reference for the clinical treatment of liver cancer.

Objective:To investigate the risk factors of postoperative recurrence of parastomal hernia repair.Methods:The clinical and follow-up data of 128 patients undergoing parastomal hernia repair at the the Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technology from Jan 1, 2013 to Dec 31, 2022 was analyzed retrospectively.Results:Postoperative recurrence was confirmed in 32 patients during follow-up, and the recurrence rates were 13.8% , 24.8% and 25.0% at 1',3' and 5 years .Univariate analysis showed that body mass index (BMI) , chronic obstructive pulmonary disease (COPD), type of stoma, prophylactic stoma displacement, and surgical options were the risk factors for recurrence after parastomal hernia repair. Multiple Logistic regression analysis showed that BMI, COPD, prophylactic stoma displacement, and surgical options were independent risk factors for the recurrence after parastomal hernia ( P< 0.05). Conclusion:The occurrence of hernia recurrence after parastomal hernia repair is closely related to patients' BMI, COPD, prophylactic stoma displacement and the surgical options.

Objective To explore the application of MRI in the differential diagnosis of high-and low-risk thymoma.Methods The data of patients with pathologically confirmed thymoma were collected bidirectionally,and the differences in clinical data,MRI image characteristics of lesions,signal characteristics and apparent diffusion coefficient(ADC)values were compared and analyzed between high-and low-risk thymoma according to the pathological subtype.The receiver operating characteristic(ROC)curve analysis was used to screen out meaningful features,then the diagnostic efficacy and combined prediction probability of indicators were evaluated.Results There was no significant difference in clinical data(P＞0.001).The morphology of high-risk lesions was mainly irregular,while that of low-risk lesions was mainly regular.The edges of high-risk lesions were mostly not smooth,and the edges of low-risk lesions were mostly smooth.The enhancement degree of high-risk lesions was higher than that of low-risk lesions,and the ADC value was lower than that of low-risk lesions,with statistical significance(P＜0.001),in which the ADC value area under the curve(AUC)was higher than other indicators(AUC=0.968),and the combined prediction probability of indicators was the highest(AUC=0.981).Conclusion MRI shows great potential application value in preoperative differential diagnosis of high-and low-risk thymoma.

Objective:To compare the differences in distribution and prognosis of cervical cancer patients in the 2009 and 2018 editions of International Federation of Gynecology and Obstetrics (FIGO) staging, and to analyze the prognostic factors of cervical cancer patients.Methods:The clinical data of 524 cervical cancer patients admitted to the First Affiliated Hospital of Soochow University from January 2010 to December 2018 were retrospectively analyzed. The cases were staged according to the 2009 and 2018 FIGO staging, and the Kendall τb coefficient was calculated to compare the consistency of the distribution of the two stages. Kaplan-Meier was used for survival analysis, and log-rank test was used to test the difference of prognosis in each stage. Cox-regression was used to analyze the prognostic factors of cervical cancer patients.Results:In the 2009 FIGO edition of staging, 1 case of stage ⅠB1 was reduced to stage ⅠA1 due to the microscopic infiltration depth <5 mm, 51 cases of stage ⅠB1 were raised to stage ⅠB2 due to 2 cm4 cm. A total of 119 cases raised to stage ⅢC1 due to pelvic lymph node metastasis, and 11 cases raised to stage ⅢC2 due to para-aortic lymph node metastasis. The distribution of cases in the two stages was consistent (τb=0.61, P<0.001). There were statistically significant differences in overall survival (OS) ( χ2=107.13, P<0.001; χ2=93.02, P<0.001; χ2=92.74, P<0.001) and progression-free survival (PFS) ( χ2=91.95, P<0.001; χ2=77.69, P<0.001; χ2=73.27, P<0.001) among patients with different stages of FIGO in 2018 (ⅠA, ⅠB, Ⅱ, ⅢA, ⅢB, ⅢC1, ⅢC2, Ⅳ) and 2009 (ⅠA, ⅠB, Ⅱ, ⅢA, ⅢB, Ⅳ) and patients with different T stages (T 1, T 2, T 3, T 4). There were statistically significant differences in OS ( χ2=20.71, P<0.001) and PFS ( χ2=24.25, P<0.001) in 2018 FIGOⅠB and ⅢC stages, and there was a statistically significant difference in OS between stage ⅢC1 and stage ⅠB2 ( χ2=6.18, P=0.013). Multivariate analysis showed that age ( HR=1.88, 95% CI: 1.08-3.28, P=0.026), pathological type ( HR=2.11, 95% CI: 1.04-4.27, P=0.038), lymph node metastasis ( HR=2.18, 95% CI: 1.34-3.56, P=0.002), parametrial spread ( HR=2.56, 95% CI: 1.52-4.29, P<0.001), maximum tumor diameter ( HR=1.98, 95% CI: 1.18-3.30, P=0.009), squamous cell carcinoma antigen (SCCA) positive after treatment ( HR=4.49, 95% CI: 2.09-9.68, P<0.001) and Hemoglobin (HB) level before treatment ( HR=0.58, 95% CI: 0.35-0.96, P=0.035) were independent risk factors for OS in patients with cervical cancer. According to the 2018 FIGO stage, the 5-year OS rates of patients with stage ⅠB1, ⅠB2, ⅠB3 were 100%, 97.1% and 87.9% respectively, with a statistically significant difference ( χ2=7.79, P=0.020), and there was a statistically significant difference between stage ⅠB1 and ⅠB3 ( χ2=5.55, P=0.019). According to the 2009 FIGO stage, the 5-year OS rates of patients with stage ⅠB1 and ⅠB2 were 95.7% and 84.3% respectively, with a statistically significant difference ( χ2=9.08, P=0.003). For patients with 2018 FIGO stage ⅠB, SCCA positive after treatment ( HR=1 172.50, 95% CI: 10.37-132 554.51, P=0.003) was an independent risk factor for OS, and differentiation degree ( HR=0.09, 95% CI: 0.01-0.81, P=0.032), treatment method ( HR=0.17, 95% CI: 0.04-0.71, P=0.015) and SCCA positive after treatment ( HR=190.68, 95% CI: 14.27-2 547.67, P<0.001) were independent risk factors for PFS. For patients with 2018 FIGO stage ⅠB, stage ( HR=9.56, 95% CI: 2.38-38.32, P=0.001), SCCA positive after treatment ( HR=126.32, 95% CI: 12.36-1 290.60, P<0.001) and lymph node metastasis ( HR=20.07, 95% CI: 3.63-111.11, P=0.001) were independent risk factors for OS, and differentiation degree ( HR=0.11, 95% CI: 0.02-0.63, P=0.013), treatment method ( HR=0.22, 95% CI: 0.06-0.75, P=0.015) and SCCA positive after treatment ( HR=43.83, 95% CI: 7.94-241.84, P<0.001) were independent risk factors for PFS. According to the 2018 FIGO stage, the 5-year OS rates of patients with stage ⅡA and ⅡB were 95.7% and 75.6% respectively, with a statistically significant difference ( χ2=13.96, P<0.001). The 5-year PFS rates of patients with stage ⅡA and ⅡB were 83.1% and 67.1% respectively, with a statistically significant difference ( χ2=7.61, P=0.006). According to the 2009 FIGO stage, the 5-year OS rates of patients with stage ⅡA and ⅡB were 90.9% and 75.0% respectively, with a statistically significant difference ( χ2=8.85, P=0.003). The 5-year PFS rates of patients with stage ⅡA and ⅡB were 75.7% and 66.7% respectively, with a statistically significant difference ( χ2=4.07, P=0.044). For patients with 2018 FIGO stage Ⅱ, pathological type ( HR=20.28, 95% CI: 2.93-140.32, P=0.002) and stage ( HR=4.35, 95% CI: 1.02-18.55, P=0.047) were independent risks factors for OS. For patients with 2009 FIGO stage Ⅱ, pathological type ( HR=5.82, 95% CI: 1.62-20.94, P=0.007) was an independent risk factor for OS, and pathological type ( HR=3.09, 95% CI: 1.22-7.85, P=0.017) and lymph node metastasis ( HR=2.07, 95% CI: 1.22-3.51, P=0.007) were independent risk factors for PFS. For patients with 2018 FIGO stage Ⅲ, maximum tumor diameter ( HR=3.31, 95% CI: 1.45-7.56, P=0.005) and SCCA positive after treatment ( HR=4.67, 95% CI: 1.22-17.86, P=0.024) were independent risk factors for OS, and pathological type ( HR=4.15, 95% CI: 1.47-11.77, P=0.007) and SCCA positive after treatment ( HR=3.96, 95% CI: 1.45-10.86, P=0.007) were independent risk factors for PFS. Conclusion:The 2018 and 2009 FIGO staging have a good distribution consistency in the cervical cancer patients, and the 2018 FIGO stage ⅠB has more advantages in judging the prognosis, but stage ⅢC cannot accurately judge the prognosis. Lymph node metastasis and maximum tumor diameter are more important prognostic factors.

Humans ; Nephrectomy ; Hemostatics/therapeutic use* ; Laparoscopy ; Kidney Neoplasms/surgery* ; Minimally Invasive Surgical Procedures

Genome-scale metabolic network model (GSMM) is an extremely important guiding tool in the targeted modification of industrial microbial strains, which helps researchers to quickly obtain industrial microbes with specific traits and has attracted increasing attention. Here we reviewe the development history of GSMM and summarized the construction method of GSMM. Furthermore, the development and application of GSMM in industrial microorganisms are elaborated by using four typical industrial microorganisms (Bacillus subtilis, Escherichia coli, Corynebacterium glutamicum, and Saccharomyces cerevisiae) as examples. In addition, prospects in the development trend of GSMM are proposed.
Corynebacterium glutamicum/genetics* ; Escherichia coli/genetics* ; Metabolic Engineering ; Metabolic Networks and Pathways/genetics*

Objective:To explore the clinical pathological characteristics and initial 131I curative responses of familial differentiated thyroid cancer (FDTC) and sporadic differentiated thyroid cancer (SDTC). Methods:A total of 66 FDTC patients (19 males, 47 females, age (39.8±11.7) years) and 1 701 SDTC patients (442 males, 1 259 females, age (40.9±11.3) years) who underwent 131I therapy in Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2010 and August 2018 were retrospectively enrolled. The clinical pathological characteristics, preablative stimulated thyroglobulin (ps-Tg), preablative stimulated thyroglobulin antibody (ps-TgAb) and response to initial therapy (excellent response, indeterminate response, biochemical incomplete response, structural incomplete response) of two groups were analyzed and compared. The clinical pathological parameters included age, gender, pathological type, tumour maximum diameter, bilateral, multifoci, nodules goiter, thyroiditis, thyroid membrane invasion, lymph node metastasis (LNM), invasion of the surrounding soft tissues, distant metastasis, TNM staging and American Thyroid Association (ATA) risk stratification (low-risk, intermediate-risk, high-risk). χ2 test or Fisher exact test and independent-sample t test were used to compare the data between two groups. Results:Comparing with SDTC group, FDTC group showed higher proportion of bilateral foci (45.5%(30/66) vs 31.2%(530/1 701); χ2=5.999, P=0.010), thyroid membrane invasion (43.9%(29/66) vs 26.6%(452/1 701); χ2=9.672, P=0.002) and distant metastasis (15.2%(10/66) vs 6.2%(105/1 701); χ2=8.418, P=0.004). There was a statistical difference in risk stratification between two groups (high-risk: 18.2%(12/66) vs 9.2%(156/1 701); intermediate-risk: 68.2%(45/66) vs 72.7%(1 237/1 701); low-risk: 13.6%(9/66) vs 18.1%(308/1 701); χ2=6.898, P=0.030). But the tumor maximum diameter of FDTC group was smaller than that of SDTC group ((1.24±0.74) vs (1.50±0.92) cm; t=-2.275, P=0.020). There were no significant differences in other clinical pathological parameters between FDTC group and SDTC group ( t=-0.804, χ2 values: 0.101-5.359, all P>0.05). There were no significant differences between two groups in the postoperation ps-Tg, ps-TgAb levels and the response to initial therapy after 131I treatment ( χ2 values: 0.059-1.915, all P>0.05). Conclusions:The FDTC group displays distinct characteristics as increased aggressiveness at diagnosis. But after accurately treatment, there is no significant difference in the response to therapy between two groups.

Objective:To establish a standard colorectal neoplasm tissue biobank with complete clinical information to provide high quality samples for fundamental and clinical research of colorectal neoplasm.Methods:Based on Affiliated Jinhua Hospital, Zhejiang University School of Medicine, to conduct structural design of colorectal neoplasm tissues, normal tissues and related information. Establish standard operating procedures from the collection and storage of tissue samples, standardize the entry of basic information, medical history, pathology and other relevant clinical information of the patients, and conduct random quality inspections on the pathological morphology and molecular level on a regular basis.Results:A tissue biobank of colorectal neoplasm was successfully constructed. During the establishment and improvement of this tissue biobank, standardized quality control was implemented during the whole-process including sample collection, warehousing, storage and delivery. According to the random sampling quality inspection, the RNA preservation effect was good, the rates of neoplasms in cancer tissue was >80%, and the clinical data of samples were complete.Conclusions:The preliminary construction of colorectal neoplasm tissue biobank not only improves the utilization value of tissue samples, but also provides a guarantee for realizing the bidirectional transformation of fundamental research and clinical application.

Objective:To explore the effect of miR-223-3p regulating FOXO3a-mediated autophagy in hepatic injury-reperfusion injury (LIRI).Methods:The model of hepatic ischemia-reperfusion injury (IR) was established in C57BL6 mice. According to different reperfusion timepoints, mice were randomly divided into 2 h, 6 h, 12 h and 24 h group. For sham group, there was no intraoperative clamping of hepatic pedicle. Murine hepatic AML12 cells were treated with miR-223-3p mimics, miR-223-3p inhibitor and FOXO3a interfering RNA. A hypoxic 1 h reoxygenation 6 h model was established. And miRNA-NC, miR-223-3p mimics, miR-223-3p inhibitor and siRNA-NC and FOXO3a siRNA groups were assigned. Hepatic injury and apoptosis were detected by hematoxylin eosin or TdT-mediated nick end labeling (HE/TUNEL) at different timepoints. The changes of proliferating cell nuclear antigen (PCNA) and Caspase-3 in hepatocytes were detected by immunohistochemistry. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were employed for detecting the expressions of miR-223-3p, FOXO3a, LC3, p62 and Caspase-3 in hepatocytes.Results:The results of HE/TUNEL indicated that reperfusion injury and apoptosis of hepatic tissue were most severe in 12 h group. In hepatic ischemia-reperfusion model, RT-PCR results showed that the expressions of miR-223-3p and FOXO3a were higher in IR group than those in sham group (1.00±0), the expression level of miR-223-3p mRNA peaked at 12 h (9.13±2.12) after reperfusion and FOXO3a was the highest at 6 h (5.23±0.90, P<0.05). Western blot showed that the expression of FOXO3a peaked at 6 h post-reperfusion and the expressions of LC3 and caspase-3 were the highest at 12 h. ( P<0.05). In the model of cell hypoxia and reoxygenation, RT-PCR indicated that the expression of FOXO3a mRNA decreased in miR-223-3p mimics group (0.45±0.21) as compared with miRNA-NC group (1.00±0). In contrast, miR-223-3p inhibitor group increased (2.73±0.53, P<0.05). Western blot indicated that FOXO3a protein expression was highest in miR-223-3p inhibitor and miR-223-3p mimics groups whereas LC3 and Caspase-3 were the highest in miR-223-3p mimics group ( P<0.05). The expression of FOXO3a was higher in siRNA-NC group than that in FOXO3a siRNA group while the expressions of Caspase-3 and LC3 were the higher in FOXO3a siRNA group. Conclusions:FOXO3a has protective effect on hepatic ischemia-reperfusion injury. It may be related to its inhibition of autophagy and apoptosis and miR-223-3p promotes injury through a down-regulation of FOXO3a-mediated autophagy. It suggests that miR-223-3p and FOXO3a are negatively correlated and may be potential gene therapeutic targets for hepatic injury.