[Significance of TERT promoter mutation in differential diagnosis of non-invasive inverted urothelial lesions of bladder].

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.

Attenuating Neuronal Autophagy Alleviates Inflammatory Injury in OGDDeprived Co-culture of HT22 with BV2.

Neuronal CX3CL1 suppressed microglial inflammation by binding to its receptor CX3CR1 expressed on microglia. Neuronal autophagy was prominently activated by cerebral ischemia, whereas CX3CL1 expression in autophagic neurons was conversely down-regulated to exacerbate microglial inflammation. Accordingly, this study was meant to investigate whether ischemia-activated microglial inflammation could be repressed by promoting CX3CL1 expression via the attenuation of neuronal autophagy. Immunofluorescence showed that autophagy predominantly occurred in neurons but barely in microglia. Western blot and immunofluorescence demonstrated that attenuating HT22 autophagy significantly increased its CX3CL1 expression and subsequently mitigated the BV2-mediated inflammatory responses, as indicated by decreased inflammatory factors of NF-κB-p65, IL-6, IL-1ß, TNF-α, and PGE2. Meanwhile, CCK-8, Nissl staining, and FJC staining showed that an OGD (Oxygen-glycogen deprivation)-created neuronal injury was greatly alleviated by CX3CL1-suppressed microglial inflammation. Contrarily, elevating HT22 autophagy markedly decreased its CX3CL1 expression, which consequently worsened microglial inflammation and the neuronal injury. Our data suggests that attenuating neuronal autophagy may be an effective method to alleviate a microglial inflammatory injury after an ischemic stroke.

[Clinicopathological and molecular diagnostic features of early-onset gastric cancer: a study based on data from a single-center dedicated gastric cancer database].

Objective: To clarify the clinicopathological, especially molecular, features of early-onset gastric cancer with the aim of informing analysis of treatment strategies. Methods: In this retrospective case-control study, we examined data from a dedicated gastric cancer database in Zhongshan Hospital affiliated to Fudan University. The original cohort comprised 2506 patients with gastric cancer who had undergone gastrectomy in Zhongshan Hospital Fudan University from July 2020 to October 2021, including 198 with early-onset gastric cancer (aged ≤45 years) and 2,308 with non-early gastric cancer. We used a simple random sampling method to select 396 of the 2,308 patients aged >45 years (ratio of 1:2) as the control group and then compared molecular diagnostic data and clinicopathological features of the two groups. Results: The median age was 39 years in the early-onset gastric cancer group, while 66 years in the control group. The clinicopathological features of early-onset gastric cancer included female predominance (59.1% [117/198] vs. 27.8% [110/396], χ2=54.816, P<0.001), less comorbidity (32.3% [64/198] vs. 57.1% [226/396], χ2=32.355, P<0.001), poorer differentiation (93.9% [186/198] vs. 74.5% [295/396], χ2=30.777, P<0.001) and higher proportion of diffuse type (40.4% [80/198] vs. 15.9% [63/396], χ2=69.639, P<0.001), distant metastasis (7.1% [14/198] vs. 2.8% [11/396], χ2=6.034, P=0.014). Regarding treatment, distal gastrectomy was more commonly performed than proximal gastrectomy (55.1% [109/198] vs. 47.0% [186/396], 1.5% [3/198] vs. 8.3% [33/396], χ2=11.644, P=0.003). Family history of gastric cancer, TNM stage, tumor size, lymph node dissection, nerve invasion, nodes harboring metastases, range of lymph node dissection, digestive tract reconstruction procedure, implementation of laparoscopic surgery, combined resection, and preoperative treatment did not differ significantly between the two groups (all P>0.05). Molecular diagnosis showed there was a smaller percentage of mismatch repair deficiency in the early-onset gastric cancer than in the control group (1.0% [2/198] vs. 10.1% [40/396], χ2=16.301, P<0.001), and a higher rate of positivity for Claudin 18.2 (77.8% [154/198] vs. 53.0% [210/396], χ2=5.442,P<0.001). HER-2 and Epstein-Barr virus positivity rates did not differ significantly between the two groups. Conclusion: Early-onset gastric cancer is a distinct type of gastric cancer with a high degree of malignancy, and treatment targeting Claudin 18.2 may be effective.

[Takayasu arteritis with pulmonary artery involvement initially presenting as community-acquired pneumonia].

The initial clinical manifestations of pulmonary artery involvement in Takayasu arteritis were complicated and non-specific, making early diagnosis difficult. Three cases of Takayasu arteritis with pulmonary artery involvement (TA-PAI) initially presenting as community-acquired pneumonia (CAP) were reported. The clinical characteristics and lab test results of the three cases were summarized, and the relevant literature on TA-PAI mimicking CAP was concomitantly reviewed. It might be helpful in the early recognition and diagnosis of such patients.

Genistein attenuates renal ischemia-reperfusion injury via ADORA2A pathway.

BACKGROUND: Studies have shown oxidative stress and apoptosis are the main pathogenic mechanisms of renal ischemia/reperfusion (IR) injury (IRI). Genistein, a polyphenolic non-steroidal compound, has been extensively explored in oxidative stress, inflammation and apoptosis. Our research aims to reveal the potential role of genistein on renal IRI and its potential molecular mechanism both in vivo and in vitro. METHODS: In vivo experiments, mice were pretreated with or without genistein. Renal pathological changes and function, cell proliferation, oxidative stress and apoptosis were measured. In vitro experiments, overexpression of ADORA2A and knockout of ADORA2A cells were constructed. Cells proliferation, oxidative stress and apoptosis were analyzed. RESULTS: Our results in vivo showed that the renal damage induced by IR was ameliorated by genistein pretreatment. Moreover, ADORA2A was activated by genistein, along with inhibition of oxidative stress and apoptosis. The results in vitro showed that genistein pretreatment and ADORA2A overexpression reversed the increase of apoptosis and oxidative stress in NRK-52E cells induced by H/R, while the knockdown of ADORA2A partially weakened this reversal from genistein treatment. CONCLUSIONS: Our results demonstrated that genistein have a protective effect against renal IRI by inhibiting oxidative stress and apoptosis via activating ADORA2A, presenting its potential use for the treatment of renal IRI.

[Clinicopathological characteristics of Klinefelter syndrome: a testicular biopsy analysis of 87 cases].

Objective: To investigate the clinicopathological characteristics of testicular biopsies from Klinefelter syndrome (KS) patients. Methods: The testicular biopsy specimens of 87 patients with KS (a total of 107 biopsy specimens) were collected from the Department of Pathology, Peking University Third Hospital, Beijing, China from January 2017 to July 2022. All patients were diagnosed as KS by peripheral blood karyotyping analysis. The testicular histopathologic features, testicular volume and hormone levels were evaluated retrospectively. The histopathologic analysis was used to assess the quantity and morphology of Leydig cells, the spermatogenic state of seminiferous tubules, the thickening of the basement membrane of seminiferous tubules and the changes of stroma. Results: Leydig cell proliferative nodules were seen in 95.3% (102/107) of KS testicular biopsy tissues. The eosinophilic inclusion bodies and lipofuscin in Leydig cells were found in 52.3% (56/107) and 57.9% (62/107) of specimens, respectively. The Sertoli cell only seminiferous tubules and the hyalinized tubules were found in 66.4% (71/107) and 76.6% (82/107) of the examined tissues, respectively. The tubules with complete spermatogenic arrest were found in 15.9% (17/107) of specimens, and 5.6% (6/107) of the specimens showed low spermatogenesis or incomplete spermatogenic arrest. In 85.0% (91/107) of the specimens, increased thick-walled small vessels with hyaline degeneration were identified. Conclusions: The most common features of KS testicular specimens are Leydig cell proliferative nodules, hyaline degeneration of seminiferous tubules and proliferation of thick-walled blood vessels. Testicular biopsy specimens of KS are rare. The pathologists can make a tentative diagnosis of KS based on the histological findings, combined with the ultrasound and laboratory results, which is helpful for further diagnosis and treatment of KS.

[Outcomes of fluoroscopy-free hip arthroscopy technique in the treatment of femoroacetabular impingement syndrome].

Objective: To evaluate the effect of fluoroscopy-free technique in the arthroscopic treatment of femoroacetabular impingement syndrome (FAIS). Methods: A retrospective cohort study. Clinical data of FAI patients treated with hip arthroscopy in the No.4 Medical Center, PLA General Hospital from October 2018 to December 2021 were retrospectively analyzed. The patients were divided into two groups according to the surgical procedure: the fluoroscopy group and the fluoroscopy-free group. The operation time and modified Harris hip score (mHHS), international hip outcome tool (iHOT12) and visual analogue scale (VAS) of hip joint pain before and after the operation were observed and compared between the two groups. And the incidence of surgical complications in the two groups were compared too. Results: A total of 460 patients (213 males and 247 females) [aged (32.6±8.3) years (15-67 years)] with valid follow-up were included in this study. There were 275 cases in the fluoroscopy-free group and 185 cases in the fluoroscopy group. The operation time was shorter in the fluoroscopy-free group when compared with that in the fluoroscopy group, and the difference was statistically significant [(93.36±12.54) min vs (115.62±6.03) min, P<0.001]. In both groups, the VAS scores decreased and the mHHS scores and iHOT12 scores improved significantly at the last follow-up when compared with those before the operation (all P<0.001); however, there was no significant difference in the scores between the two groups (all P>0.05). The complication rate in the fluoroscopy-free group was 10.18% (28/275), and it was 10.81%(20/185) in the fluoroscopy group (P=0.829). Conclusion: Fluoroscopy-free hip arthroscopy technique for FAI can avoid radiation and shorten the operation time, but it does not increase the incidence of complications with reliable clinical outcomes.

[IgG4-related diseases of retroperitoneum in urinary and male reproductive system: a clinicopathological analysis of eleven cases].

Objective: To analyze the clinicopathological features of IgG4-related diseases (RD) of retroperitoneum and the urinary and male reproductive system (IgG4-RUMR). Methods: A total of 11 IgG4-RUMR cases from January 2013 to March 2021 were retrospectively collected at Peking University Third Hospital and Shandong Provincial Hospital affiliated to Shandong First Medical University. The clinicopathologic features, laboratory and imaging findings were analyzed and scored according to the 2019 ACR/EULAR classification criteria for IgG4-RD. Results: The 11 patients (male:female is 9∶2; mean age 59 years, range from 44 to 83 years) were initially admitted to the Deparment of Urology/Kidney Transplantation (10 cases) and the Department of Oncology (1 case). All patients had urogenital disorders or imaging abnormalities. Three of the 11 patients had a history of IgG4-RD such as lacrimal gland engorgement, salivary gland engorgement and IgG4-associated pancreatitis. Abnormal retroperitoneal soft tissue and hydronephrosis were found in eight cases, while epididymal and spermatic cord masses were found in one case, simple renal mass in one case, and"benign prostatic hyperplasia"in one case. In the 10 patients tested for serum IgG4, the serum IgG4 level was 0.8-14.4 g/L. Histologically, all cases showed significant lymphoplasmacytic infiltration and storiform fibrosis, and some were accompanied by obliterative phlebitis. The number of IgG4 positive plasma cells was 12-155 per high-power field, and the IgG4/IgG ratio was 15%-77%. According to the 2019 ACR/EULAR IgG4-RD classification standard 11 cases scored 20-48 points, all of which met the diagnostic criteria of IgG4-RUMR. Therapeutically, the patient with a simple renal mass underwent partial nephrectomy. The patient with prostate lesion underwent transurethral resection of prostate and was initially diagnosed as nonspecific chronic prostatitis. Later, the patient was admitted again because of salivary gland swelling, and the pathologic diagnosis was amended. The patient with epididymal and spermatic cord masses participated in a clinical trial about retroperitoneal fibrosis. The remaining eight patients received symptomatic treatment such as adhesiolysis and stent placement. All the patients were subsequently treated with glucocorticoid/immunosuppressant and symptoms relieved. Conclusions: IgG4-RUMR is uncommon. In clinical practice, information from clinical, serologic, radiologic and pathologic evaluations must be integrated. IgG4-RUMR should be considered in the differential diagnosis of urinary and male reproductive diseases. The 2019 ACR/EULAR classification criteria for IgG4-RD, while relatively complex, are objective and practical in the diagnosis of IgG4-RUMR.

[A case-control study of multiple myeloma patients with central nervous system involvement].

Objective: To investigate the treatment options for multiple myeloma patients with central nervous system involvement (CNS-MM) , as well as their clinical characteristics and prognostic factors. Methods: Between January 2011 and January 2022 our center diagnosed 18 people with CNS-MM. A retrospective analysis was done on the clinical information from the initial diagnosis and central nervous system involvement, and it was compared to 1∶3 matched newly diagnosed MM from the same period. Analysis was done on the clinical characteristics and survival rates of the two groups. Results: In patients with CNS-MM, the median time of onset was 14.2 (0.9-79.6) months and the median overall survival (OS) was 30.5 months from initial diagnosis and only 3.8 months in patients after CNS involvement. The CNS-MM patients showed more IgD type (P=0.010) , severer anemia (P=0.014) , a higher proportion of bone marrow plasma cells (P=0.013) , more extramedullary lesions (P=0.001) , and increased lactic dehydrogenase (LDH) (P=0.009) when compared to the control group. Lenalidomide or pomalidomide-based combinations had higher rates of hematology and CNS remission than bortezomib or daratumumab-based regimens (75.0% vs 16.7% , P=0.019) . Patients who received IMiD-based regimens and had 2 high-risk factors at initial diagnosis (high LDH and extramedullary lesions) had a significantly lower incidence of CNS-MM (P=0.026) . At the initial diagnosis, LDH (P=0.008, HR=7.319, 95% CI 1.663-32.219) and extramedullary lesions (P=0.006, HR=8.054, 95% CI 1.828-35.486) were independent risk factors for the occurrence of CNS-MM. Conclusion: Patients with CNS-MM had a poor prognosis. Patients with high LDH or extramedullary lesions at the time of the initial diagnosis are more likely to have CNS-MM. The prognosis of this patient may be improved by immunoregulator-based therapy.

Associations between severe pulmonary function and residual CT abnormalities in rehabilitating COVID-19 patients.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) spread around the world in 2020. Abnormal pulmonary function and residual CT abnormalities were observed in COVID-19 patients during recovery. Appropriate rehabilitation training is around the corner. The correlation between spirometric impairment and residual CT abnormality remains largely unknown. PATIENTS AND METHODS: A cross-sectional study conducted on the pulmonary function of 101 convalescent COVID-19 patients before discharge. Multivariate analysis was used to establish a scoring system to evaluate the spirometric abnormality based on residual chest CT. RESULTS: Lung consolidation area >25% and severe-type COVID-19 were two independent risk factors for severe pulmonary dysfunction. Besides, a scoring system was established. People scoring more than 12 points have more chances (17 times) to get severe pulmonary function impairment before discharge. CONCLUSIONS: For the first time, a chest CT characteristics-based grading system was suggested to predict the pulmonary dysfunction of COVID-19 patients during convalescence in this study. This study may provide suggestions for pulmonary rehabilitation.

[Clinical and pathological features of renal cell carcinoma with urinary tract tumor thrombus: 6 cases report and literature review].

OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment of renal cell carcinoma with urinary tract tumor thrombus. METHODS: From January 1, 2015 to December 31, 2019, patients with renal cell carcinoma complicated with urinary tract tumor thrombus who were hospitalized in the Peking University Third Hospital and Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. Meanwhile, we reviewed the literature, and the reported patients of renal cell carcinoma with urinary tract tumor thrombus were also included in our study. The basic information, clinical manifestations, treatment, pathological characteristics and follow-ups of all the patients were analyzed. RESULTS: In our study, 6 patients from the two hospitals and 16 patients from previous literature reports were included. There were 13 males and 9 females with an average age of 54.7 years (22-79 years). Fifteen patients had renal cell carcinoma on the left side, 6 on the right side, and 1 on the unknown side. Gross hematuria was the most common chief complaint, including 18 patients. One patient complained of weight loss, 1 patient complained of microscopic hematuria, and 1 patient was found by ultrasound examination. Tumor thrombus was classified as grade Ⅰ in 9 cases (the tumor embolus protruded into the renal pelvis, but did not reach the ureteropelvic junction), grade Ⅱ in 10 cases (the tumor embolus protruded into the ureter, but not into the bladder), and grade Ⅲ in 3 cases (the tumor embolus passed through the ureter and protruded into the bladder). Only 11 patients were diagnosed with renal cell carcinoma before operation. Radical nephrectomy was performed in 9 cases and nephroureterectomy in 12 cases. In pathological diagnosis, there were 15 cases of clear cell renal cell carcinoma, 1 case of papillary renal cell carcinoma, 1 case of chromophobe cell carcinoma, 1 case of mixed cell renal cell carcinoma, 4 cases of renal cell carcinoma with undetermined classification. Eleven patients were followed up for 3-31 months, and 3 patients had lung metastasis within 6 months. CONCLUSION: Renal cell carcinoma with urinary tract tumor thrombus is rare in clinic. It needs to be differentiated from renal pelvis carcinoma in diagnosis. The treatment principle can refer to general renal carcinoma. For locally advanced cases, complete resection is the best treatment, and its oncological prognosis needs more long-term and large-scale follow-up observation.