Nonalcoholic steatohepatitis （NASH） is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration， and it plays an important role in the progression of hepatic steatosis. Recent studies have shown that immune homeostasis imbalance between T helper 17 （Th17） and regulatory T （Treg） cells are closely associated with the pathological process of NASH. Transforming growth factor-β1 （TGF-β1） is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells， and TGF-β1 binds to its receptor and activates the Smad signaling pathway， thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation. This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells， in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective To investigate the value of extracellular volume fraction(ECV)based on CT for predicting macrotrabecular-massive hepatocellular carcinoma(MTM-HCC).Methods Data of 23 MTM-HCC(MTM-HCC group)and 56 non-MTM-HCC(nMTM-HCC group)patients were retrospectively analyzed,and CT manifestations were compared between groups.CT values of abdominal aorta(P-CTabdominal aorta,E-CTabdominal aorta),tumors(P-CTtumor,E-CTtumor)and non-tumor liver parenchyma(P-CTliver,E-CTliver)in plain phase(P)and enhancement equilibrium phase(E)CT were measured,then ECV of tumors and liver parenchyma were calculated,and ECV-related parameters were compared between groups.Receiver operating characteristic curves were drawn,and area under the curve(AUC)was calculated to evaluate the predictive efficacy of ECV-related parameters for predicting MTM-HCC.Results No significant difference of CT manifestations was found between groups(all P＞0.05).E-CTtumor,Δltumor(absolute enhancement CT value of the tumor area)and ECVtumor in MTM-HCC group were all lower than those in nMTM-HCC group(all P＜0.01).The AUC of E-CTtumor,Δtumor and ECVtumor for predicting MTM-HCC was 0.74,0.77 and 0.87,respectively,and the AUC of ECVtumor was higher than that of E-CTtumor and Δtumor(Z=2.271,2.557,P=0.023,0.011).Conclusion ECV based on CT could be used to effectively predict MTM-HCC.

Objective:To investigate the efficacy of Peritoneal interposition flap (PIF) technique in preventing postoperative pelvic lymphocele formation during laparoscopic radical prostatectomy with extended pelvic lymph node dissection (LRP+ ePLND).Methods:A retrospective analysis was conducted on clinical data of 113 patients with locally high-risk or locally advanced prostate cancer who underwent LRP+ ePLND at Shanghai East Hospital, from January 2020 to November 2023. Among them, 27 patients received PIF technique and 86 received traditional LRP+ ePLND. ePLND was carried out as the clearance of external iliac vessels, medial side of the internal iliac artery, and pararectal lymph nodes. The PIF technique was the suturing the peritoneal flap after freeing the bladder to the lateral side of the bladder, pulling the peritoneal edge that follows the bladder's free edge posteriorly to the pubis, curling it onto the lateral surface of the bladder. This could expose the lymph node clearance bed, establishing a pathway from the lymph node clearance bed to the abdominal cavity space, allowing exuded lymphatic fluid to flow into the abdominal cavity for absorption by the peritoneum. There were no statistically significant differences in age [(68.37±6.92)years vs.(70.47±5.72)years], body mass index [(25.47±2.49)kg/m 2vs.(24.46±2.80)kg/m 2], and preoperative PSA [(23.28±13.94)ng/ml vs.(24.81±13.99)ng/ml] between the PIF group and the control group ( P>0.05). Biopsy Gleason score in PIF group: 6 in 2 cases, 7 in 9 cases, 8 in 9 cases, 9-10 in 2 cases. Biopsy Gleason score in control group: 6 in 4 cases, 7 in 35 cases, 8 in 27 cases, 9-10 in 20 cases. Clinic stage in PIF group: T 2 in 18 cases, T 3 in 6 cases, T 4 in 3 cases. Clinic stage in control group: T 2 in 51cases, T 3 in 27 cases, T 4 in 8 cases. The preoperative Gleason scores and TNM staging comparisons between the PIF group and the control group showed no statistically significant differences ( P>0.05). Surgical duration, intraoperative blood loss, lymph node positivity rate, incidence of postoperative lymphocele, and recovery of urinary control were compared between the two groups. Results:All surgeries were completed successfully without intraoperative complications in both groups. There were no statistically significant differences between the PIF group and the control group in terms of surgical duration [(202.96±24.15)min vs.(201.1±29.85)min], intraoperative blood loss [(85.56±32.27)ml vs.(90.7±49.25)ml], and lymph node positivity rate [(4 in PIF group, 14.8%)vs.(25 in control group, 29.1%)]( P>0.05). Urinary catheters were retained for 10-14 days postoperatively. Following catheter removal, there were no statistically significant differences in urinary control rates at 1 month [51.85%(14/27)vs. 48.83%(42/86)]and 2 months[74.07%(20/27) vs. 72.09%(62/86)] between the PIF group and the control group ( P>0.05). At the 2 to 6-month follow-up CT scan, none of the 27 patients in the PIF group developed pelvic lymphocele, whereas 9 patients in the control group did (6 cases bilateral, 3 cases unilateral), showing a statistically significant difference between the two groups ( P=0.002). Postoperatively, 3 patients in the control group experienced symptoms, with 1 case of lymphocele infection causing fever 1 month after surgery. Lymphocysts were found in 2 patients with ipsilateral lower extremity swelling 2 weeks after surgery. Conclusions:The application of PIF technique during laparoscopic radical prostatectomy with extended pelvic lymph node dissection via the abdominal approach could be safe and feasible. It may prevent postoperative pelvic lymphocele formation.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Objective:This study aimed to investigate the effect of lipohypertrophy induced by insulin injection on blood glucose fluctuation in patients with type 1 diabetes mellitus.Methods:A total of 80 patients with type 1 diabetes mellitus were recruited between June 2021 and December 2021 from the First Affiliated Hospital of Nanjing Medical University. And these patients all received insulin injection more than six months. Lipohypertrophy was assessed by ultrasound scanning, and blood glucose fluctuation was evaluated using the flash glucose monitoring system(FGM). Univariate analysis and multivariate linear regression were used to analyze the relationship of lipohypertrophy and and core indicators of blood glucose fluctuation.Results:Compared with patients without lipohypertrophy, patients with lipohypertrophy had higher mean amplitude of glycemic excursions(MAGE), coefficient of variation(CV), mean of daily differences(MODD), standard deviation(SD) of blood glucose, time above range(TAR), and high blood glucose index(HBGI; all P<0.05), while time in range(TIR) of glucose markedly become lower( P<0.01). Moreover, multivariate linear regression analysis showed that lipohypertrophy detected by ultrasound was an independent influencing factor of TIR( β=-9.423, P=0.032), MAGE( β=1.114, P=0.039), CV( β=4.304, P=0.041), MODD( β=0.717, P=0.046) after adjusting for age at diagnosis, duration of insulin injection, fasting C-peptide, and daily dose of insulin per unit weight. Conclusion:Lipohypertrophy increases glycemic variability and imposes negative impact on glycemic control rate in patients type 1 diabetes mellitus.

Objective:To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis.Methods:In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed.Results:The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 28.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome.Conclusions:Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

Objective To explore the important factors influencing organ donation willingness and coordination effect of organ donation coordinators. Methods A questionnaire survey was conducted among 349 national organ donation coordinators by convenience sampling, including 145 males and 204 females, aged 27 (23, 36) years. Multiple linear regression and disordered logistic regression were used to investigate the important factors influencing the willingness to donate organs and coordination effects. Results Among 349 organ donation coordinators, 146 (41.8%) were willing to donate organs, including 101 (28.9%) who had signed the consent card for organ donation. Adequate awareness of organ donation laws, high education level, marital experience, and good self-perceived health status all showed positive effects on organ donation willingness of organ donation coordinators (all P < 0.05). High income, long length of service as organ donation coordinators, full-time mode of employment, high willingness to donate organs, and adequate awareness of donation conditions and donation procedures all showed positive effects on the coordination effect of organ donation coordinators (all P < 0.05). Conclusions The willingness to donate organs is increased as the higher awareness of organ donation laws of organ donation coordinators, while enhancing the willingness to donate organs of organ donation coordinators exerts positive impact upon improving the coordination effect of organ donation coordination. Therefore, an all-round organ donation coordinator training system should be established to improve the success rate of organ donation advocacy and promote the development of organ donation.

Objective: To investigate the causative factors of renal function in newly diagnosed multiple myeloma (MM) patients with renal inadequacy. Methods: 181 MM patients with renal impairment from August 2007 to October 2021 at Peking Union Medical College Hospital were recruited, whose baseline chronic kidney disease (CKD) stage was 3-5. Statistical analysis was performed based on laboratory tests, treatment regimens, hematological responses, and survival among various renal function efficacy groups. A logistic regression model was employed in multivariate analysis. Results: A total of 181 patients were recruited, and 277 patients with CKD stages 1-2 were chosen as controls. The majority choose the BCD and VRD regimens. The progression-free survival (PFS) (14.0 months vs 24.8 months, P<0.001) and overall survival (OS) (49.2 months vs 79.7 months, P<0.001) of patients with renal impairment was considerably shorter. Hypercalcemia (P=0.013, OR=5.654) , 1q21 amplification (P=0.018, OR=2.876) , and hematological response over a partial response (P=0.001, OR=4.999) were independent predictive factors for renal function response. After treatment, those with improvement in renal function had a longer PFS than those without (15.6 months vs 10.2 months, P=0.074) , but there was no disparity in OS (56.5 months vs 47.3 months, P=0.665) . Conclusion: Hypercalcemia, 1q21 amplification, and hematologic response were independent predictors of the response of renal function in NDMM patients with renal impairment. MM patients with CKD 3-5 at baseline still have worse survival. Improvement in renal function after treatment is attributed to the improvement in PFS.
Humans ; Multiple Myeloma/drug therapy* ; Bortezomib/therapeutic use* ; Hypercalcemia ; Prognosis ; Chromosome Aberrations ; Kidney/physiology* ; Renal Insufficiency, Chronic ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols

Humans ; Aortic Dissection ; Aorta