The clinical applications of acrosin activity are limited. We analyzed 61 578 male partners in infertile couples who visited the outpatient department of the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) between August 2014 and December 2019 to determine the reference ranges and thresholds for acrosin activity in infertile Chinese men; to determine whether correlations exist between acrosin activity and age, sperm concentration, sperm morphology, or sperm motility; and to evaluate whether acrosin activity could serve as an effective prognostic indicator for choosing between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in the clinic. The cut-off value for the normal reference range of acrosin activity for male partners in infertile couples was 24.78 μIU per 106 sperm. There was no significant association between acrosin activity and age, sperm concentration, semen volume, total sperm count, progressive motility, or total motile spermatozoa. A weak positive correlation was found between acrosin activity and normal sperm morphology. There was a statistically significant difference in abnormal acrosome morphology between the group with high acrosin activity (>24.78 μIU per 106 sperm) and the group with low acrosin activity (<24.78 μIU per 106 sperm). The group with a low IVF fertilization rate had a high index of abnormal acrosomal morphology at 21.2%, while the group with a high IVF fertilization rate had a low index of 0.2%. At an acrosin activity of <24.78 µIU per 106 sperm, in one cycle of the same patient, the fertilization rate, normal fertilization rate, and good-quality embryo rate for ICSI were significantly higher than those for IVF. Therefore, the most promising application of acrosin activity could be in the selection of ICSI over IVF for infertile male patients with complete fertilization failure or a low fertilization rate.

Objective: To analyze the impact of the sinonasal anatomic changes after endonasal endoscopic anterior skull base surgery on the nasal airflow and heating and humidification by computational fluid dynamics (CFD), and to explore the correlation between the postoperative CFD parameters and the subjective symptoms of the patients. Methods: The clinical data in the Rhinology Department of the First Affiliated Hospital of Zhengzhou University from 2016 to 2021 were retrospectively analyzed. The patients received the endoscopic resection of the anterior skull base tumor were selected as the case group, and the adults whose CT scans had no sinonasal abnormalities were chosen as the control group. The CFD simulation was performed on the sinonasal models after reconstructed from the patients' sinus CT images during the post-surgical follow-up. All the patients were asked to complete the Empty Nose Syndrome 6-Item Questionnaire (ENS6Q) to assess the subjective symptoms. The comparison between two independent groups and the correlation analysis were carried out by using the Mann-Whitney U test and the Spearman correlation test in the SPSS 26.0 software. Results: Nineteen patients (including 8 males and 11 females, from 22 to 67 years old) in the case group and 2 patients (a male of 38 years old and a female of 45 years old) in the control group were enrolled in this study. After the anterior skull base surgery, the high-speed airflow moved to the upper part of the nasal cavity, and the lowest temperature shifted upwards on the choana. Comparing with the control group, the ratio of nasal mucosal surface area to nasal ventilation volume in the case group decreased [0.41 (0.40, 0.41) mm^-1 vs 0.32 (0.30, 0.38) mm^-1; Z=-2.04, P=0.041], the air flow in the upper and middle part of the nasal cavity increased [61.14 (59.78, 62.51)% vs 78.07 (76.22, 94.43)%; Z=-2.28, P=0.023], the nasal resistance decreased [0.024 (0.022, 0.026) Pa·s/ml vs 0.016 (0.009, 0.018) Pa·s/ml; Z=-2.29, P=0.022], the lowest temperature in the middle of the nasal cavity decreased [28.29 (27.23, 29.35)℃ vs 25.06 (24.07, 25.50)℃; Z=-2.28, P=0.023], the nasal heating efficiency decreased [98.74 (97.95, 99.52)% vs 82.16 (80.24, 86.91)%; Z=-2.28, P=0.023], the lowest relative humidity decreased [(79.62 (76.55, 82.69)% vs 73.28 (71.27, 75.05)%; Z=-2.28, P=0.023], and the nasal humidification efficiency decreased [99.50 (97.69, 101.30)% vs 86.09 (79.33, 87.16)%; Z=-2.28, P=0.023]. The ENS6Q total scores of all patients in the case group were less than 11 points. There was a moderate negative correlation between the proportion of the inferior airflow in the post-surgical nasal cavity negatively and the ENS6Q total scores (r_s=-0.50, P=0.029). Conclusions: The sinonasal anatomic changes after the endoscopic anterior skull base surgery alter the nasal airflow patterns, reducing the efficiency of nasal heating and humidification. However, the post-surgical occurrence tendency of the empty nose syndrome is weak.
Adult ; Humans ; Male ; Female ; Young Adult ; Middle Aged ; Aged ; Retrospective Studies ; Hydrodynamics ; Air Conditioning ; Nose ; Nasal Cavity ; Skull Base/surgery*

Objective:To investigate the effect of miRNA (miR) -193b-5p on melanogenesis and its possible mechanisms.Methods:Human primary melanocytes were isolated from discarded normal foreskin tissues of healthy males after circumcision, and cultured in vitro. miR-NC mimics (miR-NC mimic group) and miR-193b-5p mimics (miR-193b-5p mimic group) were transfected into human primary melanocytes and human MNT1 melanoma cells, separately. After transfection, real-time quantitative PCR (RT-qPCR) was performed to determine the overexpression efficiency of miR-193b-5p at 48 hours, Western blot analysis to determine the expression of melanogenesis-related proteins tyrosinase (TYR) and microphthalmia-associated transcription factor (MITF) in human primary melanocytes and human MNT1 melanoma cells at 72 hours, and the melanin content in the above cells was determined by a sodium hydroxide solubilization method at 1 week. The target gene of miR-193b-5p was predicted by using Targetscan algorithms and verified by dual-luciferase reporter assay, and RT-qPCR and Western blot analysis were performed to analyze changes in mRNA and protein expression of the target gene respectively after the overexpression of miR-193b-5p. Two-independent-samples t test was used for comparisons between two groups. Results:In human primary melanocytes and human MNT1 melanoma cells, the miR-193b-5p expression levels were significantly higher in the miR-193b-5p mimic groups than in the miR-NC mimic groups ( t = 65.57, 22.49, respectively, both P < 0.001) , and the melanin content was significantly lower in the miR-193b-5p mimic groups (0.091 ± 0.007, 0.130 ± 0.004, respectively) than in the miR-NC mimic groups (0.117 ± 0.002, 0.188 ± 0.032, t = 5.98, 3.24, P < 0.01, < 0.05, respectively) . Western blot analysis showed that the expression of melanogenesis-related proteins TYR and MITF in both human primary melanocytes and human MNT1 melanoma cells was significantly lower in the miR-193b-5p mimic groups than in the miR-NC mimic groups (all P < 0.01) . TargetScan analysis and dual-luciferase reporter assay revealed a binding site for miR-193b-5p in the 3′ untranslated region of the transcriptional regulator CITED2. After up-regulation of miR-193b-5p expression in human primary melanocytes and human MNT1 melanoma cells, the CITED2 mRNA and protein expression levels significantly decreased compared with the miR-NC mimic groups (all P < 0.05) . Conclusion:miR-193b-5p overexpression can down-regulate the expression of melanogenesis-related proteins TYR and MITF, and then inhibit melanogenesis, which may be related to the targeted inhibition of CITED2 expression.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

A 3-year-old boy presented with bluish patch and scattered blue spots on the left side of his face. After several sessions of laser treatment, the azury patch in the periorbital area became even darker. Histopathology showed many bipolar, pigment-laden dendritic cells scattered in the papillary and upper reticular dermis. Immunohistochemically, these cells were positive for S100, SOX-10, melan-A, P16, and HMB-45. The positive rate of Ki-67 was less than 5%. Finally, the lesion was diagnosed with nevus of Ota concurrent with common blue nevus. Therefore, for cases of the nevus of Ota with poor response to laser treatment, the possible coexisting diseases should be suspected.
Male ; Humans ; Child, Preschool ; Nevus, Blue/pathology* ; Nevus of Ota/therapy* ; Skin/pathology* ; Face ; Skin Neoplasms/pathology*

In this study, the critical quality attributes of Wuzhuyu Decoction reference sample were explored by using characteristic chromatogram, index component content and dry extract rate as indexes.The dissemination relationship of quantity value between medicinal materials-decoction pieces-reference sample was investigated to preliminarily formulate the quality standard of the reference sample.The characteristic chromatogram of 15 batches of Wuzhuyu Decoction was established by high performance liquid chromatography(HPLC) and the similarity analysis was conducted.Common peaks were demarcated and assigned to medicinal materials.Moreover, quantitative determination of limonin, evodiamine, rutaecarpine and ginsenoside Rb_1 of Wuzhuyu Decoction were performed.The dissemination of quantity value was explored combined with dry extract rate, similarity of characteristic chromatogram and transfer rate of index component content.A total of 18 common peaks were identified in the corresponding materials of Wuzhuyu Decoction reference sample, with the similarity of characteristic chromatogram greater than 0.9, and Fructus Evodiae, Radix Ginseng, Rhizoma Zingiberis Recens and Fructus Jujubae contributed 9, 5, 8 and 2 chromatographic peaks, respectively.The index component content of corresponding materials and the transfer rates of medicinal materials-decoction pieces and decoction pieces-reference sample of different batches of Wuzhuyu Decoction reference sample were as follows: the content of limonin was 0.16%-0.51%, and the transfer rates were 83.66%-115.60% and 38.54%-54.58%, respectively; the content of evodiamine was 0.01%-0.11%, the transfer rated were 80.80%-116.15% and 3.23%-12.93%, respectively; the content of rutaecarpine was 0.01%-0.05%, the transfer rates were 84.33%-134.53% and 5.72%-21.24%, respectively; the content of ginsenoside Rb_1 was 0.06%-0.11%, and the transfer rates were 90.00%-96.92% and 32.45%-67.24%, respectively.The dry extract rate of the whole prescription was 22.58%-29.89%.In this experiment, the dissemination of quantity value of Wuzhuyu Decoction reference sample was analyzed by the combination of characteristic chromatogram, index component content and dry extract rate.A scientific and stable quality evaluation method of the reference sample was preliminarily established, which provided basis for the subsequent development of Wuzhuyu Decoction and the quality control of related preparations.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Ginsenosides/analysis* ; Limonins/analysis* ; Quality Control

Depression is a serious mental illness with a high incidence. At present, we do not fully understand the specific pathological mechanisms of depression, and the efficacy of drug treatments is very limited. Recent studies have shown that epigenetic changes that occur in specific brain regions may be a key mechanism by which environmental factors to interact with individuals to influence the risk of depression. Therefore, drugs that target epigenetic regulation may become a new direction for the development of antidepressants. Histone deacetylase inhibitors (HDACi) are a class of compounds that inhibit histone deacetylase activity, which has been reported to be associated with depression; this article addresses the use of HDACi in preclinical studies, and their potential therapeutic role and limitations of use in depression.

Hyperuricemia is a chronic metabolic disease caused by the accumulation of uric acid in the body caused by purine metabolism disorder. In recent years, the incidence of hyperuricemia has increased and the age of onset is showing a younger trend. Finding effective therapeutic targets and treatment methods is a hot spot of current research. The urate transporter ATP-binding cassette subfamily G member 2 (ABCG2) is mainly expressed in the kidney and promotes uric acid excretion. In this study, ABCG2 mRNA was synthesized in vitro and transfected into hyperuricemia model mice to observe its effect on mouse uric acid levels. Firstly, the DNA template of ABCG2 mRNA was chemically synthesized, and then transcribed into mRNA in vitro, followed by modification and transfection into mouse TCMK-1 renal tubular epithelial cells. Finally, the protein expression in the cells was detected by Western blot. The results showed that the amount of protein expression in TCMK-1 cells was positively correlated with the amount of transfected mRNA (P < 0. 01), indicating a successful transfection. In animal experiments, twenty-four SPF mice were randomly divided into four groups (n = 6): control group, hyperuricemia model group, benzbromarone group [20 mg/(kg•d)] and mRNA group [2 mg/(kg•3d)]. The mice have been modeled and treated for 28 days. During this period, the body weight and growth status of the mice were monitored daily. After the treatment, the levels of serum uric acid, urine uric acid, serum creatinine, blood urea nitrogen and liver xanthine oxidase were analyzed. The results showed that compared with the model group of mice, mRNA treatment can significantly reduce the levels of serum uric acid (100. 38 ± 10. 94), blood urea nitrogen (6. 30 ± 1. 10), and serum creatinine (30. 86 ± 5. 78, P<0. 05 or P<0. 01). It can also increase the level of urine uric acid (617. 48 ± 50. 34, P<0. 05) in mice and promote the excretion of uric acid. But it has no significant effect on the activity of xanthine oxidase (26. 19 ± 2. 58) in the liver. The pathological changes of mice kidney were observed by HE staining. The results showed that compared with mice in the model group, pathological damages such as renal tubular cell edema and inflammatory cell infiltration in the mRNA treatment group were significantly improved. The relative expression of mRNA in mice kidney was detected by qRT-PCR, and the protein expression of ABCG2 in mice kidney was detected by immunohistochemistry and Western blot. The results showed that the relative expression of ABCG2 mRNA and its protein were significantly up-regulated in the kidney tissues of mice in the mRNA group (P < 0. 01), indicating that the transfection was successful in vivo. In conclusion, ABCG2 mRNA synthetized and modified in vitro can be successfully expressed in hyperuricemia mice and promote excretion of uric acid and other organic ions, as well as improvement of renal injury in mice. These results provide experimental basis for the clinical application of ABCG2 as a target for the treatment of hyperuricemia related diseases.

Objective:To understand the current situation of physicians′ competency in China and statistically analyze its influencing factors, hence providing referential evidences for promoting their competency.Methods:The evaluation scale for Chinese physicians′ competency was developed by referring to sophisticated overseas evaluation frameworks. Based on the electronic platform of the medical alliance, stratified sampling was conducted at 39 hospitals in 13 provinces, from which 2 156 physicians were surveyed, and statistical analysis was made on the current situation and influential factor of their competency in 6 dimensions(medical knowledge, diagnosis and treatment, scientific research and teaching, interpersonal communication, spirit of professionalism, population health)Results:The score range in multiple dimensions of physicians′ competency was between 2.85 and 3.89(5 in total), among which spirit of professionalism dimension scores the highest, and teaching and research dimension scores the lowest. Logistic regression analysis shows that their competency level in 6 dimensions is correlated to a range of factors, including gender, degree, title, supervisor qualifications, standardized training program of specialist physicians, and affiliation or not to teaching hospitals( P<0.05). Conclusions:Their overall competency is expected to be elevated. To name a few, they are lack of teaching and research abilities, and need to conduct clinical-oriented scientific research; they are expected to enrich knowledge structure, and need to embrace a wider concept of health; they need to improve their non-technical service abilities, and should further emphasize their humanistic quality; physicians′ practice competency depends upon their extent of medical education, and ensuring the quality of standardized training becomes the key measure.

Objective:To construct an artificial intelligence model for the diagnosis of facial vitiligo, so as to realize artificial intelligence-assisted diagnosis of facial vitiligo.Methods:Based on digital single-lens reflex (SLR) camera images of vitiligo skin lesions and YOLO (You Only Look Once) v3 algorithm, a skin lesion detection model Vit3 was established, and its performance was evaluated by comparing its detection results and labeling results of dermatologists. On the basis of the Vit3 model, both optical and ultraviolet images of vitiligo and non-vitiligo skin lesions were taken by using an artificial intelligence-based facial skin image collector, and the gray values of vitiligo and non-vitiligo skin lesion areas on the ultraviolet images were measured by using an image processing technique. According to the gray-value threshold between vitiligo and non-vitiligo skin lesions, a facial vitiligo diagnosis model Vit4 was established. Cochran′s Q test was used to compare the diagnostic results of the Vit4 model and dermatologists, and the diagnostic performance of the Vit4 model was evaluated. Results:For 100 SLR camera images of vitiligo skin lesions (167 lesional sites) and 100 SLR camera images of normal skin, the diagnostic sensitivity of the Vit3 model was 92.81% (155/167) . For 97 pairs of facial skin images (including 50 vitiligo lesions, 30 pityriasis alba lesions, 7 amelanotic nevus leisons, and 10 normal skin tissues) , the diagnostic accuracy rate, sensitivity and specificity of the Vit4 model were 88.66% (86/97) , 88.00% (44/50) and 89.36% (42/47) respectively, and there was no significant difference in the diagnostic accuracy rate between the Vit4 model and dermatologists (92.78%[90/97], χ2=2.323, P > 0.05) . Conclusion:The artificial intelligence model Vit4 was established for the diagnosis of facial vitiligo with favorable diagnostic performance, and could serve as an objective and convenient method for the auxiliary diagnosis of facial vitiligo.