Objective:To investigate the clinicopathological features and differential diagnosis of eosinophilic vacuolated tumor (EVT).Methods:Seven cases of EVT with characteristic morphology and unequivocal diagnosis from the Affiliated Hospital of Qingdao University (6 cases), Qingdao, China and the 971 Hospital of PLA Navy (1 case), Qingdao, China between January 2010 and December 2021 were subject to morphological and immunohistochemical analyses. Additionally, whole exome sequencing (WES) was performed in two cases. Twenty-two cases of renal oncocytoma (RO) and 17 cases of eosinophilic chromophobe renal cell carcinoma (eChRCC) diagnosed at the same time were used as controls.Results:Four males and three females with a mean age of 42 years (range: 29-61 years) were included in the study. The tumors were nodular and well-circumscribed, with sizes ranging from 1.5 to 4.5 cm. On cross-section, they appeared gray-red or gray-white, solid, and soft. Tumor cells were arranged in nests, solid sheets, and acinar or small vesicular structures. These cells exhibited eosinophilic cytoplasm with large, prominent clear vacuoles and round nuclei with prominent nucleoli. Perinuclear halos were focally present in four cases, while small tumor cells with sparse cytoplasm and hyperchromatic nuclei were seen in one case. No necrosis or mitosis was noted. Edematous stroma was detected in three cases. All tumors were positive for CD117 and Cathepsin K, but negative for vimentin and CK7. CK20 was positive in scattered individual cells, and Ki-67 positivity ranged from 1% to 4%. Point mutations in MTOR were identified in both patients who were subject to the molecular analysis. Statistical differences in the expression of Cathepsin K, CD10, S-100A1, and Cyclin D1 between EVT and RO ( P<0.05) were significant, so were the differences in the expression of Cathepsin K, CD10, CK7 and claudin 7 between EVT and eChRCC ( P<0.001). Seven patients were followed up for 4 to 96 months (mean, 50 months), with no recurrences or metastases. Conclusions:EVT is a rare renal tumor that shares morphological and immunophenotypic features with RO and eChRCC, and it is closely linked to the TSC/MTOR pathway. The presence of large prominent transparent vacuoles in eosinophilic cytoplasm along with conspicuous nucleoli is its key morphological characteristics. The use of combined immunohistochemical stains greatly aids in its diagnosis. Typically, the tumor exhibits indolent biological behaviors with a favorable prognosis.

Objective:To explore the clinical features and genetic etiology for a child with developmental delay, impaired growth, facial dysmorphism, and axonal neuropathy (DIGFAN).Methods:A child who was admitted to the Second Affiliated Hospital of Guangxi Medical University on March 22, 2021 was selected the study subject. Clinical data of the child was collected. Following extraction of genomic DNA, the child and his parents were subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results:The child, a 10-year-and-9-month-old boy, had manifested with short stature, intellectual disability, delayed speech, motor and language development, and facial dysmorphism. WES and Sanger sequencing revealed that he has harbored a novel de novo c. 800T>C (p.Leu267Pro) variant of the MORC2 gene. The Leucine at position 267, which is highly conserved among various species, is located in the S5 domain of ribosome protein in the ATPase binding region of MORC2. And the Leu267Pro may affect the function of MORC2 by altering the spatial conformation and activity of ATPase. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 800T>C variant was classified as likely pathogenic (PS2+ PM2_Supporting+ PP2+ PP3). Conclusion:The MORC2: c. 800T>C (p.Leu267Pro) variant probably underlay the pathogenesis of DIGFAN syndrome in this child.

Alzheimer's disease(AD) is a refractory neurodegenerative disease clinically characterized by memory loss and cognitive and behavioral dysfunction. The main pathological features of AD include neuronal loss, β-amyloid protein(Aβ) deposition and neurofibrillary tangles (NFTs), and numerous studies have shown that these may be triggered by neuronal death and neuroinflammation Receptor-interacting serine/threonine-protein kinase 1(RIPK1) is a serine/threonine kinase present at the intersection of cell death and inflammatory signaling pathways.Studies in recent years have revealed a potential role of RIPK1 on the progress of AD. In this paper, we summarized the links between RIPK1-mediated necroptosis and AD treatment from the aspects of neuronal death, inflammasome activation, blood-brain barrier breakdown and mitochondrial dysfunction, and the targeted treatment of RIPK1, the new findings of RIPK1 inhibitors and ongoing clinical trials, aiming to provide new ideas for the treatment of AD.

Vulvovaginal candidiasis（VVC）is an opportunistic infection of the vaginal mucosa mainly caused by Candida albicans， which is the second most common vaginal infection other than bacterial vaginosis. The azole antifungal agent fluconazole is the drug of the first choice for treatment of VVC. With the widespread and non-standard use in clinical practice，the resistance of Candida albicans to fluconazole is on the rise. This article reviews the mechanisms of vaginal Candida vaginalis resistance to fluconazole，including the target mutations or high expression of drug action-related genes，the overexpression of drug efflux pump，the regulation of stress response，and the formation of biofilms，in order to provide information for a new strategy of VVC treatment.

Objective:To investigate the application of virtual reality (VR) technology on intraoperative pain in patients undergoing peritoneal dialysis (PD)-related procedures with local infiltration anesthesia and the satisfaction.Methods:It was a single-center, prospective, concurrent controlled study. Patients were divided into two groups: VR group and control group. In the VR group, patients wore a VR headset to watch soothing audio and video content during surgery, while the control group underwent routine procedures. Intraoperative pain and satisfaction were assessed using the visual analog scale (VAS) and a 5-point satisfaction scale within 30 minutes of surgery. In addition, tolerance of the VR experience in the VR group was assessed using the VR sickness questionnaire.Results:A total of 43 patients were included in the study, including 25 males (58.1%). Chronic glomerulonephritis [17 cases (39.5%)] and diabetic nephropathy [6 cases (14.0%)] were the main primary diseases. There were 23 cases in the control group and 20 cases in the VR group. There were no significant differences between the two groups in age, sex ratio, proportion of primary disease, diabetes, hypertension, distribution of operation methods, preoperative vital signs and operation time (all P>0.05). VAS pain score was significantly lower in the VR group than that in the control group (5.90±2.38 vs. 7.43±1.67, t=2.469, P=0.018). The percentage of patients who were satisfied was 89.5% (17/19) in the VR group and 78.3% (18/23) in the control group, but there was no significant difference (chi-square test for continuity correction, χ2=0.308, P=0.579). Three patients in the VR group withdrew from the study due to severe discomfort, while the remaining participants found the VR experience to be tolerable. Common adverse effects included fatigue and blurred vision. Conclusions:The application of VR technology in PD-related procedures has been effective in reducing intraoperative pain when combined with local infiltration anesthesia. Furthermore, the utilization of VR technology in PD-related procedures is associated with a safe and tolerable outcome, despite the observation of some adverse effects.

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl₄. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6C^high macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl₄-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl₄-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.

Objective:To learn about the iodine nutritional status of children aged 8 - 10 and pregnant women in Zhaoyuan City of Shandong Province, and to provide a basis for prevention and control of iodine deficiency disorders in the future.Methods:In 2008 and 2021, a census method was used to collect drinking water samples from all 724 villages (neighbourhood committee) in Zhaoyuan City. In 2018 and 2022, a multi-stage cluster random sampling method was used to investigate the daily per capita salt intake of residents. From 2017 to 2022, multi-stage random sampling method was used to collect household salt and urine samples from children aged 8 - 10 and pregnant women. Among them, thyroid volume tests were conducted on the sampled children in 2017, 2019, 2020 and 2022, and iodine supplementation surveys were conducted on the sampled pregnant women in 2019 - 2022. The iodine content in water was determined by As 3+-Ce 4+ catalytic spectrophotometry using ammonium persulfate digestion. The iodine content in potassium iodate salt was determined by direct titration method in "General Test Method in Salt Industry-Determination of Iodine" (GB/T 13025.7-2012). And other fortified iodized salt, unqualified iodized salt and non-iodized salt were retested using the redox titration method. Urinary iodine was determined by "Determination of iodine in urine - Part 1: As 3+-Ce 4+ catalytic spectrophotometry" (WS/T 107.1-2016). The children's thyroid gland was examined by using DP-2200Plus fully digital portable ultrasound instrument and 75L38EB ultrasound probe, and the goiter rate was calculated. Results:The median water iodine levels in Zhaoyuan City in 2008 and 2021 were 5.71 and 1.30 μg/L, respectively. The daily per capita salt intake of residents in 2018 and 2022 was 9.36 and 7.83 g, respectively. It is estimated that the per capita iodine intake in 2018 was (180.64 ± 71.00) μg/d and in 2022 was (124.25 ± 72.23) μg/d. From 2017 to 2022, the consumption rate of qualified iodized salt in both children and pregnant women was less than 90%; and from 2018 to 2022, the coverage rate of iodized salt was < 95%. The median urinary iodine of children was 184.00 μg/L, at an appropriate level, there was a statistically significant difference in urinary iodine content among children in different years ( H = 77.39, P < 0.001). From 2017 to 2022, the median urinary iodine of pregnant women was between 100 and 150 μg/L, there was no statistically significant difference in urinary iodine content among pregnant women in different years ( H = 5.33, P = 0.208). The goiter rate of children in 2017, 2019, 2020 and 2022 was 3.00% (24/800), there was no statistically significant difference in goiter rate among children in different years ( P = 1.000). A total of 400 pregnant women were investigated for iodine supplementation, the rate of iodine supplementation was 90.50% (362/400). Conclusions:Zhaoyuan City has reached the elimination standard for iodine deficiency disorders, but some pregnant women are at risk of iodine deficiency. Continuous monitoring and attention should be paid to the iodine nutritional status of pregnant women.

ObjectiveTo systematically evaluate the effect of action observation therapy (AOT) on upper limb function in children with cerebral palsy. MethodsRelevant literatures about the effect of AOT on upper limb function in children with cerebral palsy were retrieved from the databases of PubMed, Embase, Cochrane Library, Web of Science and CNKI, from the establishment to July 9, 2022. ResultsEleven articles involving 497 patients were included, which were mainly published in the past ten years. The studies included hospital-based studies with therapist supervision and home-based studies without therapist supervision, mainly related to the improvement of upper limb function of AOT in children with cerebral palsy. Experimental group performed actions related to activities of daily living, while control group mainly watched video clips excluding actions, 15 to 120 minutes a time, three to five times a week, with most of the intervention periods of three to four weeks. AOT improved the upper limb function of children with cerebral palsy in terms of body structure and function, and activity and participation, specifically grip strength, muscle tension, and hand dexterity and function. ConclusionHospital-based AOT with therapist supervision can improve upper limb function in children with cerebral palsy, while the effect of home-based AOT without therapist supervision and the long-term effect of AOT need to be further studied.

Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.

Objective:This study aimed to compare the detection efficacy of transrectal ultrasound-guided transrectal cognitive fusion targeted+ systematic prostate biopsy and transperineal cognitive fusion targeted + systematic biopsy in patients with suspected prostate cancer (PCa). In addition, the relative clinical characteristics of PCa were evaluated.Methods:A total of 385 patients with suspected prostate cancer in the affiliated hospital of Qingdao University from May 2019 to November 2019 were retrospectively analyzed. All patients met the prostate biopsy criterion, who underwent transrectal(n=275)and transperineal(n=110)prostate biopsy respectively. There were no significant differences of mean age [(70.7±7.3)years vs.(69.2±8.4) years], PSA [(55.12±116.96)ng/ml vs. (63.41±315.34)ng/ml], prostate volume [(55.96±35.26)ml vs. (64.35±55.99)ml] between two groups. According to preoperative prostate magnetic resonance imaging combined with intraoperative ultrasound, 2-4 needles targeted puncture of suspected lesion were performed, followed by 12 needle systematic prostate biopsy. The detection rate of prostate cancer between two biopsy ways were compared. The related factors of PCa including age, prostate volume and PSA level were collected for univariable and multivariable logistic analysis. The cancer detection rate was compared and logistic regression was used to assess the impact of patient characteristics on PCa detection.Results:For all patients, the detection rate with cancer between transrectal group and transperineal group were 121/275(40.0%) and 67/110(60.9%), respectively. The transperineal group detected a higher rate of PCa ( P=0.003)and more clinically significant prostate cancers (csPCa) (54.6% vs.36.7%, P=0.001) than that of the transrectal group, there were significant differences between two groups ( P<0.05). Univariate and multivariate logistic regression analysis revealed that PSA( OR=1.025, P=0.001) and prostate volume( OR=0.984, P=0.001)were two independent factors for the detection rate of prostate cancer between two biopsy ways( P<0.05). The effect of age on the detection rate of PCa in the transperieal group was significantly lower than that of the transrectal group( OR=0.037, P=0.238 vs. OR=0.053, P=0.002). Conclusion:The transperieal biopsy could find more PCa than the transrectal biopsy. PSA level and prostate volume could affect the detection rate of cancer between two prostate biopsy ways.