BACKGROUND: Peripheral helper T (T PH ) cells are uniquely positioned within pathologically inflamed non-lymphoid tissues to stimulate B-cell responses and antibody production. However, the phenotype, function, and clinical relevance of T PH cells in hepatocellular carcinoma (HCC) are currently unknown. METHODS: Blood, tumor, and peritumoral liver tissue samples from 39 HCC patients (Sep 2016-Aug 2017) and 101 HCC patients (Sep 2011-Dec 2012) at the Third Affiliated Hospital of Sun Yat-sen University were used. Flow cytometry was used to quantify the expression, phenotype, and function of T PH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. T PH cells, CD19 + B cells, and T follicular helper (T FH ) cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. RESULTS: T PH cells highly infiltrated tumor tissues, which was correlated with tumor size, early recurrence, and shorter survival time. The tumor-infiltrated T PH cells showed a unique ICOS hi CXCL13 + IL-21 - MAF + BCL-6 - phenotype and triggered naïve B-cell differentiation into regulatory B cells. Triggering programmed cell death protein 1 (PD-1) induced the production of C-X-C motif chemokine ligand 13 (CXCL13) by T PH cells, which then suppressed tumor-specific immunity and promoted disease progression. CONCLUSION Our study reveals a novel regulatory mechanism of T PH cell-regulatory B-cell-mediated immunosuppression and provides an important perspective for determining the balance between the differentiation of protumorigenic T PH cells and that of antitumorigenic T FH cells in the HCC microenvironment.
Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Humans ; T-Lymphocytes, Helper-Inducer/metabolism* ; Animals ; Mice ; Male ; Female ; Mice, Inbred C57BL ; Middle Aged ; B-Lymphocytes, Regulatory/metabolism* ; Flow Cytometry ; Interleukin-21 ; Aged ; Chemokine CXCL13/metabolism*

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Objective:To analyze the clinical data and genetic characteristics of a child with CLN1 neuronal ceroid lipofuscinosis in conjunct with hereditary hyperferritinemia cataract syndrome (HHCS).Methods:A child who was admitted to the PICU of the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the child was collected. Genetic testing was carried out for the child, and the result was analyzed in the light of literature review to explore the clinical and genetic characteristics to facilitate early identification.Results:The patient, a 3-year-old male, had mainly presented with visual impairment, progressive cognitive and motor regression, and epilepsy. Cranial magnetic resonance imaging revealed deepened sulci in bilateral cerebral hemispheres, and delayed myelination. The activity of palmitoyl protein thioesterase was low (8.4 nmol/g/min, reference range: 132.2 ~ 301.4 nmol/g/min), whilst serum ferritin was increased (2 417.70 ng/mL, reference range: 30 ~ 400 ng/mL). Fundoscopy has revealed retinal pigment degeneration. Whole exome sequencing revealed that he has harbored c. 280A>C and c. 124-124+ 3delG compound heterozygous variants of the PPT1 gene, which were respectively inherited from his father and mother. Neither variant has been reported previously. The child has also harbored a heterozygous c. -160A>G variant of the FTL gene, which was inherited from his father. Based on the clinical phenotype and results of genetic testing, the child was diagnosed as CLN1 and HHCS. Conclusion:The compound heterozygous variants of the PPT1 gene probably underlay the disorders in this child. For children with CLN1 and rapidly progressing visual impairment, ophthalmological examination should be recommended, and detailed family history should be taken For those suspected for HHCS, genetic testing should be performed to confirm the diagnosis.

Objective:To evaluate the effect of prophylactic octreotide administration on pancreaticoduodenectomy (PD)associated postoperative pancreatic fistula (POPF), total complications, peri-operative death and postoperative in-hospital days.Methods:From January 2020 to August 2021, 148 patients who underwent PD in the Department of Biliary-Pancreatic Surgery in Ren Ji Hospital affiliated with School of Medicine of Shanghai Jiao Tong University were recruited into this single-center randomized control double-blinded clinical trial. Patients were randomly assigned into octreotide group ( n=74) and control group ( n=74). Octreotide group was subcutaneously injected with 0.1 mg (1 ml) octreotide after preoperative anesthesia, and was subcutaneously injected with the same dose every 8 hours for 5 days, with a total of 16 doses. Control group was injected with 1 ml normal saline in the same way, and relevant clinical data and indicators of the two groups were recorded. The primary endpoint was clinically relevant pancreatic fistula, and the secondary endpoints were total complications, perioperative death and postoperative in-hospital days. Univariate and multivariate logistic regression analysis were used to screen the risk factors of clinically related POPF after PD. Results:120 patients were finally enrolled, including 61 in octreotide group and 59 in control group. There were no significant differences on age, gender ratio, body mass index, preoperative surgery rate of jaundice reduction, preoperative major biochemical indicators, operation time, intraoperative blood loss, pancreatic duct diameter, pancreatic texture and pathological type composition ratio. The total incidence of clinical relevant POPF was 8.3%, and there were no significant differences on biochemical leakage (4.9% vs 8.5%, P=0.435), grade B fistula (4.9% vs 8.5%, P=0.435) and grade C fistula (1.6% vs 1.7%, P=0.981). The total complication incidence (24.5% vs 28.8%, P=0.601), perioperative mortality (0 vs 3.3%, P=0.147) and postoperative in-hospital days (20.6±11.1 d vs 19.5±12.2 d, P=0.633) were not significantly different between two groups. Univariate analysis showed that preoperative serum albumin level <30 g/L( P<0.001) and pathological type of pancreatic ductal adenocarcinoma ( P=0.036) were independent risk factors for POPF after PD, while multivariate analysis found no statistically significant risk factors. Conclusions:Octreotide can neither reduce the incidences of POPF, total complications and postoperative mortality, nor shorten postoperative in-hospital days. However, for patients with preoperative hypoproteinemia and (or) the pathological type of pancreatic duct adenocarcinoma, the prophylactic use of octreotide during PD and after PD may reduce the occurrence of POPF.

Objective:To characterize the radial head fracture combined with capitulum cartilage injury (CCI).Methods:The data of 110 patients were analyzed retrospectively who had been treated for radial head fracture at Department of Orthopaedics, The Ninth People's Hospital of Wuxi from January 2011 to May 2020. They were 62 males and 48 females, aged from 17 to 74 years (average, 44.10 years). According to the finding of intraoperative exploration whether CCI was complicated or not, they were assigned into a CCI group and a CCI-free group. The diagnosis, location, size, type, operation method and postoperative recovery of CCI were observed in CCI group. The 2 groups were compared in terms of preoperative general data, range of forearm motion before and after operation and functional recovery of the limb by Mayo elbow performance score (MEPS).Results:CCI was complicated in 25 cases (type Ⅰ in 7 ones, type Ⅱ in 12 ones and type Ⅲ in 6 ones), involving all Mason types of radial head fracture, and located at the lateral capitellum in 13 cases, at the posterolateral capitellum in 9 cases and at the anterolateral capitellum in 3 cases. CCI was diagnosed before operation in 13 cases by physical examination after local anesthesia and imaging examination with a rate of 48% (12/25) for missed diagnosis. The preoperative flexion and extension (61.8°±13.7°) and rotation (60.0°±24.2°) in CCI group were significantly less than those in CCI-free group (77.7°±23.0° and 79.9°±21.9°) ( P<0.05); the Mason types of radial head fracture in CCI group were significantly more serious than those in CCI-free group ( P<0.05). There was no significant difference between the 2 groups in age, gender, combined injury, treatment of radial head fracture, follow-up time, range of forearm motion at the last follow-up or MEPS score ( P>0.05). Conclusions:CCI was complicated in 22.73%(25/110) of the radial head fractures in this cohort and found in all Mason types of radial head fracture, and mostly located at the lateral and posterolateral capitellum. CCI is likely to be missed by imaging examination. In patients with mild radial head fracture and suspected CCI, positive physical examination after local anesthesia is valuable for diagnosis of CCI complication and operative indication. Care should be taken to detect CCI complication by intraoperative exploration in surgery of radial head fracture.

Objective:To analyze the clinico pathological features, differential diagnosis and prognosis of metastatic renal cell carcinomas.Methods:The clinical data, histology, immunophenotype and follow-up data of 196 patients with metastatic renal cell carcinoma diagnosed from 1994 to 2017 at the Department of Pathology, Changhai Hospital, Naval Military Medical University, Shanghai, China were analyzed retrospectively.Results:There were 142 males and 54 females, with a median age of 61 years. The top three metastatic sites for the 196 cases of metastatic renal cell carcinoma were lung (31.1%, 61/196), bone (29.1%, 57/196) and digestive system (19.4%, 38/196). Among the pathological subtypes of metastasis, the proportion of clear cell renal cell carcinoma was 94.4% (185/196) and that of type II papillary renal cell carcinoma was 3.6% (7/196). The TFE3 translocated renal cell carcinoma and congestive tubular carcinoma were rare, with 3 cases and 1 case, respectively. CK, vimentin, CAⅨ and CD10 were expressed in all metastatic clear cell renal cell carcinomas. CK7, CD10 and P504s were expressed in papillary renal cell carcinomas. TFE3 was expressed in TFE3 translocated renal cell carcinoma. The collecting duct carcinoma was positive for HCK.Conclusions:Lung metastasis and bone metastasis are still the most frequent metastatic sites of renal cell carcinoma. Five years after primary lesion resection may be the high risk time for metastasis. Most of the metastases are solitary when they are first identified. To better diagnose and identify the renal origin of a metastatic renal cell carcinoma, one should consider morphological characteristics, clinical history information of the metastasis and the combined immunohistochemistry of CK, vimentin, CD10, CK7, TFE3, PAX2 and PAX8.

Objective: Preliminary study on the clinical effect of preoperative ultrasound endoscopy combined with staining labeling technique to locate the actual boundary of esophageal and gastric cancer Methods: From September 1, 2015 to October 30, 2017, 18 patients with esophageal adenocarcinoma were enrolled in this study. The actual boundaries of esophageal and gastric-derived adenocarcinoma lesions were localized by endoscopic ultrasonography and staining. There were 10 males and 8 females. After completing the preoperative examination, 1-2 days before operation, endoscopic ultrasonography was used to locate the edge of the lesion. Two point injection of carbon nano suspension was used to mark the location of 1cm at the longest distance from the longitudinal axis of the tumor. According to the length of longitudinal axial staining, the thoracotomy was performed. Intraoperative proximal margin resection was used to send frozen pathology. According to the results of freezing, the operation was decided. After the operation, the specimens from the margin of the tumor were segmented into paraffin section, which was about 0.5cm in each segment, and the tumor cells were observed under the electron microscope at all levels of the paraffin sections. Results: The average time of preoperative endoscopic ultrasonography staining was(10.16±1.38) min, and the diameter of nano carbon diffusion was(1.43±0.41)cm. All patients in the operation could clearly see the nano carbon staining area under the naked eye. In the field, the average time of locating lesions was(1.27±0.53)min. 5 patients underwent thoracoabdominal surgery and 13 underwent abdominal surgery. The average length of the cut margin of the tumor was(4.74±1.12)cm, and the frozen pathology of the incision margin was negative, and no additional operation was performed. The routine pathology confirmed that all the specimens were negative. Conclusion The staining and labeling technique for adenocarcinoma of the esophagogastric junction under endoscopic ultrasonography can detect the tumor edge and the scope of invasion accurately. It provides guidance and guarantee for the smooth implementation of AEG precision surgery. It is a safe, rapid and effective positioning technique.

Objective To evaluate the prognostic value of preoperative neutrophil-to lymphocyte ratio (NLR) in invasive breast carcinomas of no special type.Methods we retrospectively analyzed the clinical and pathological data of all breast cancer patients at Shanghai Huangpu District Cental Hospital from Jan.2012 to Dec.2012.The optimal cutoff value was obtained by ROC.The difference among variables was calculated by chi-square test.DFS and OS were estimated using Kaplan-Meier method.Cox analysis was performed to analyze clinical parameters for their prognostic relevance.Results A total of 493 were eligible.The optimal cutoff value of NLR was 2.057.The sensitivity was 0.767 and specifity was 0.327 at the optimal cutoff point.Univariate analysis showed that patients with NLR higher than 2.057 had significantly lower DFS (P=-0.001) than patients with NLR equal or lower than 2.057,while the overall survival rate was not statistically different (P=0.131).The Cox proportional multivariate hazard model revealed that higher NLR was independently related with poor DFS with hazard ratio 5.649(95％ confidence interval 3.128-10.201,P=0.002).Conclusions Preoperative NLR is an independent predictor of DFS in breast cancer patients.Further validation and a feasibility study are required before it can be considered for clinical use.

Objective To evaluate the effect of Tandospirone citrate in the treatment of Alzheimer's disease with depression and anxiety disorder. Methods A total of 122 patients with Alzheimer's disease with depression and anxiety were enrolled at the Second Hospital of Jinhua City from January 2015 to December 2016.They were randomly divided into the Lorazepam group(n=61) and the Tandospirone citrate(ADHA)(n= 61).The behavioral pathology in Alzheimer's disease (BEHAVE-AD),self-care ability scale(ADL),Hamilton anxiety scale(HAMA)and Hamilton depression scale(HAMD)were evaluated in the two groups after three weeks of treatment.The BEHAVE-AD,ADL,HAMA,and HAMD scores and the incidence of adverse reactions were compared between the two groups before and after treatment. Results Baseline scores of BEHAVE-AD, ADL,HAMA and HAMD were not significantly different between the two groups(all P> 0.05). However,post-treatment scores of BEHAVE-AD,ADL,HAMA and HAMD were significantly lower than pre-treatment scores(all P< 0.05),and were more significantly decreased in the Tandospirone citrate group(all P<0.05).Furthermore,the incidence of adverse reactions was significantly lower in the Tandospirone citrate group than that in the Lorazepam group(6.5% vs.19.7%,P< 0.05). Conclusions Compared with Lorazepam,Tandospirone citrate is clinically more effective for Alzheimer's disease complicated with anxiety and depressive disorder.

BACKGROUND: We previously showed that the expression of follistatin-like protein 1 (FSTL1) was significantly down-regulated in metastatic clear-cell renal cell carcinoma (ccRCC). In this study, we aimed to characterize the role of FSTL1 in the development of ccRCC. METHODS: The effects of FSTL1 on cell activity and cell cycle were investigated in ccRCC cell lines with altered FSTL1 expression. Gene expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 knockdown. The expression of FSTL1 in ccRCC and its effect on postoperative prognosis were estimated in a cohort with 89 patients. RESULTS: FSTL1 knockdown promoted anchorage-independent growth, migration, invasion, and cell cycle of ccRCC cell lines, whereas FSTL1 overexpression attenuated cell migration. FSTL1 knockdown up-regulated nuclear factor-κB (NF-κB) and hypoxia-inducible factor (HIF) signaling pathways, increased epithelial-to-mesenchymal transition, up-regulated interleukin-6 expression, and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor (IκBα) in ccRCC cell lines. FSTL1 immunostaining was selectively positive in epithelial cytoplasm in the loop of Henle, and positive rate of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues (P < 0.001). The multivariate Cox regression analysis showed that the intratumoral FSTL1 expression conferred a favorable independent prognosis with a hazard ratio of 0.325 (95% confidence interval 0.118-0.894). HIF-2α expression was negatively correlated with FSTL1 expression in ccRCC specimens (r = - 0.229, P = 0.044). Intratumoral expression of HIF-2α, rather than HIF-1α, significantly predicted an unfavorable prognosis in ccRCC (log-rank, P = 0.038). CONCLUSIONS FSTL1 plays a tumor suppression role possibly via repressing the NF-κB and HIF-2α signaling pathways. To increase FSTL1 expression might be a candidate therapeutic strategy for metastatic ccRCC.
Adult ; Aged ; Aged, 80 and over ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Carcinoma, Renal Cell ; genetics ; pathology ; Cell Line, Tumor ; Cell Movement ; genetics ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; genetics ; Female ; Follistatin-Related Proteins ; genetics ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; Male ; Middle Aged ; NF-kappa B ; genetics ; Neoplasm Metastasis ; Signal Transduction ; genetics ; Tumor Suppressor Proteins ; genetics