Noise-induced hearing loss is a worldwide public health issue that is characterized by temporary or permanent changes in hearing sensitivity. This condition is closely linked to inflammatory responses, and interventions targeting the inflammatory gene tumor necrosis factor-alpha (TNFα) are known to mitigate cochlear noise damage. TNFα-induced proteins (TNFAIPs) are a family of translucent acidic proteins, and TNFAIP6 has a notable association with inflammatory responses. To date, there have been few reports on TNFAIP6 levels in the inner ear. To elucidate the precise mechanism, we generated transgenic mouse models with conditional knockout of Tnfaip6 (Tnfaip6 cKO). Evaluation of hair cell morphology and function revealed no significant differences in hair cell numbers or ribbon synapses between Tnfaip6 cKO and wild-type mice. Moreover, there were no notable variations in hair cell numbers or hearing function in noisy environments. Our results indicate that Tnfaip6 does not have a substantial impact on the auditory system.
Animals ; Mice, Knockout ; Hair Cells, Auditory, Inner/pathology* ; Mice ; Mice, Transgenic ; Hearing Loss, Noise-Induced ; Evoked Potentials, Auditory, Brain Stem/physiology*

Ovarian follicle expansion is an important part of their growth and development into dominant follicles,and is regulated by a variety of molecules and signals,including follicular cavity formation,follicular fluid accumulation,and granulosa cell proliferation.Polycystic ovary syndrome(PCOS)is the most common reproductive endocrine disease in women,and patients mainly present with increased preantral follicles and polycystic ovarian lesions caused by inadequate ovarian follicle expansion.This review summarizes recent research developments concerning the physiological process of ovarian follicle expansion and the related regulatory factors and mechanisms.We also consider the possible factors restricting ovarian follicle expansion in patients with PCOS,to provide a theoretical basis for follicular dysplasia,ovulation disorders and other diseases caused by abnormal ovarian follicle expansion.

Ovarian follicle expansion is an important part of their growth and development into dominant follicles,and is regulated by a variety of molecules and signals,including follicular cavity formation,follicular fluid accumulation,and granulosa cell proliferation.Polycystic ovary syndrome(PCOS)is the most common reproductive endocrine disease in women,and patients mainly present with increased preantral follicles and polycystic ovarian lesions caused by inadequate ovarian follicle expansion.This review summarizes recent research developments concerning the physiological process of ovarian follicle expansion and the related regulatory factors and mechanisms.We also consider the possible factors restricting ovarian follicle expansion in patients with PCOS,to provide a theoretical basis for follicular dysplasia,ovulation disorders and other diseases caused by abnormal ovarian follicle expansion.

AIM:To explore the role and mechanism of natriuretic peptide A(NPPA)/natriuretic peptide re-ceptor 1(NPR1)signaling in luteinizing hormone(LH)-induced ovarian follicle expansion in mice.METHODS:Three-week-old female mice were injected with pregnant mare serum gonadotropin/equine chorionic gonadotrophin(eCG)48 h before use to stimulate follicle development,or injected with eCG followed by human chorionic gonadotropin(hCG)treat-ment for 4 or 8 h,with 6 mice in each group.Periodic acid-Schiff(PAS)staining in ovarian sections was used to observe the follicular diameter,and qPCR was used to detect the expression of Npr1 mRNA levels in granulosa cells.Wild-type(WT)and Npr1 knockout(Npr1-/-)mice were injected with eCG,or injected with eCG followed by hCG treatment for 4 h.PAS staining was used to observe the follicular diameter,with 6 mice in each group.Superovulation and fertility assays were performed to count the number of ovulated oocytes and pups,with 6 mice in each group subjected to superovulation and 7 mice in each group subjected to fertility assays.The isolated follicles were randomly divided into control,NPPA,LH,LH+NPPA,LH+NPPA+KT5823[protein kinase G(PKG)inhibitor],and LH+NPPA+PPQ-102[cystic fibrosis transmembrane conductance regulator(CFTR)inhibitor]groups,with 20 follicles in each group.In addition,WT and Npr1-/-mice were injected with eCG 48 h or eCG 48 h/hCG 4 h,with 3 mice in each group.In vitro follicle culture and qP-CR were used to explore the effects of PKG and CFTR signalling on NPPA/NPR1-induced follicular expansion.The prolif-eration of granulosa cells in WT and Npr1-/-mice was detected via immunofluorescence staining,with 5 mice in each group.RESULTS:The results revealed that hCG treatment significantly increased the follicle expansion and Npr1 mRNA expression in granulosa cells(P<0.01).The capacity for ovarian follicle expansion,the number of ovulations,and the number of pups per litter were significantly lower in Npr1-/-mice compared with WT mice(P<0.01).In in vitro follicular culture,the addition of PKG inhibitor KT5823 and CFTR inhibitor PPQ-102 significantly inhibited NPPA/NPR1-induced ovarian follicle expansion(P<0.01),and the expression of Pkg mRNA and Cftr mRNA in granulosa cells of Npr1-/-mice was significantly lower than that in WT mice(P<0.01).In addition,the proliferation ability of granulosa cells in Npr1-/-mice was significantly lower than that in WT mice(P<0.01).CONCLUSION:LH promotes mouse ovarian follicle ex-pansion by NPPA/NPR1 signalling-induced PKG and CFTR pathways and granulosa cell proliferation.

AIM:To explore the role and mechanism of natriuretic peptide A(NPPA)/natriuretic peptide re-ceptor 1(NPR1)signaling in luteinizing hormone(LH)-induced ovarian follicle expansion in mice.METHODS:Three-week-old female mice were injected with pregnant mare serum gonadotropin/equine chorionic gonadotrophin(eCG)48 h before use to stimulate follicle development,or injected with eCG followed by human chorionic gonadotropin(hCG)treat-ment for 4 or 8 h,with 6 mice in each group.Periodic acid-Schiff(PAS)staining in ovarian sections was used to observe the follicular diameter,and qPCR was used to detect the expression of Npr1 mRNA levels in granulosa cells.Wild-type(WT)and Npr1 knockout(Npr1-/-)mice were injected with eCG,or injected with eCG followed by hCG treatment for 4 h.PAS staining was used to observe the follicular diameter,with 6 mice in each group.Superovulation and fertility assays were performed to count the number of ovulated oocytes and pups,with 6 mice in each group subjected to superovulation and 7 mice in each group subjected to fertility assays.The isolated follicles were randomly divided into control,NPPA,LH,LH+NPPA,LH+NPPA+KT5823[protein kinase G(PKG)inhibitor],and LH+NPPA+PPQ-102[cystic fibrosis transmembrane conductance regulator(CFTR)inhibitor]groups,with 20 follicles in each group.In addition,WT and Npr1-/-mice were injected with eCG 48 h or eCG 48 h/hCG 4 h,with 3 mice in each group.In vitro follicle culture and qP-CR were used to explore the effects of PKG and CFTR signalling on NPPA/NPR1-induced follicular expansion.The prolif-eration of granulosa cells in WT and Npr1-/-mice was detected via immunofluorescence staining,with 5 mice in each group.RESULTS:The results revealed that hCG treatment significantly increased the follicle expansion and Npr1 mRNA expression in granulosa cells(P<0.01).The capacity for ovarian follicle expansion,the number of ovulations,and the number of pups per litter were significantly lower in Npr1-/-mice compared with WT mice(P<0.01).In in vitro follicular culture,the addition of PKG inhibitor KT5823 and CFTR inhibitor PPQ-102 significantly inhibited NPPA/NPR1-induced ovarian follicle expansion(P<0.01),and the expression of Pkg mRNA and Cftr mRNA in granulosa cells of Npr1-/-mice was significantly lower than that in WT mice(P<0.01).In addition,the proliferation ability of granulosa cells in Npr1-/-mice was significantly lower than that in WT mice(P<0.01).CONCLUSION:LH promotes mouse ovarian follicle ex-pansion by NPPA/NPR1 signalling-induced PKG and CFTR pathways and granulosa cell proliferation.

Objective To understand the distribution of ecological suitability of Scutellaria baicalensis Georgi;To screen the main ecological factors affecting its distribution;To predict its suitable planting area in China.Methods A total of 231 batches of Scutellaria baicalensis Georgi were collected through the fourth national survey of TCM resources.The environment information of sampling points were recorded,and 55 ecological factors were analyzed by MaxEnt model and GIS.Results Rainfall,vegetation type and soil types had a greater influence on the distribution of Scutellaria baicalensis Georgi.The ecological suitable areas of Scutellaria baicalensis Georgi mainly concentrated in the eastern part of Shaanxi Province,the western part of Hebei Province and most areas of Chengde,the most part of Shanxi Province,the western part of Beijing,the western part of Liaoning Province,the central and eastern part of Shandong Province,the junction of Jiangsu and Anhui Province,the northern part of Yunnan Province,and the eastern and southern part of Sichuan Province.Conclusion The ecological suitability areas of Scutellaria baicalensis Georgi were classified in this study,and the results could provide reference for the selection of cultivation areas of Scutellaria baicalensis Georgi.

Objective The oxidative damage of DNA can be caused by excessive levels of Reactive oxygen species(ROS).Monitoring of DNA oxidative damage enables effective evaluation of ROS damage effects.Although the detection of DNA damage effects based on microbial sensor allows quantitative analysis of oxidative damage,the ROS clearance mechanism existed in bacterial will affect the sensitive of detection.The work of this article is to knockout the key genes of ROS clearance mechanism and construct an antioxidant gene-knock-out microbial sensor.The microbial sensor can realize sensitive monitoring of DNA damage effects and then evaluates the damage effects of cells by ROS.Methods The antioxidant damage genes of bacterial ahpCF,katE and katG were knocked out by λ-Red homologous recombination and antioxidant gene-knockout microbial sensor was constructed.The nalidixic acid sodium salt and UV irradiation were used to characterize the performance for monitoring of DNA damage effects.Results The antioxidant gene-knockout microbial sensors ΔahpC,ΔahpCF/ΔkatEG and ΔahpCF/ΔkatE/ΔkatG were constructed successfully.The results showed that the microbial sensor ΔahpCF/ΔkatE/ΔkatGl had the highest sensitive of damage effects and the limit of detection for nalidixic acid sodium salt was 0.40 μmol/L.In addition,1.80 min of UV irradiation(254 nm)was sufficient to induce a significant fluorescent expression effect in the engineered bacteria.Conclusion In this article,antioxidant gene-knockout microbial sensors had been constructed to realize active and sensitive monitoring of DNA damage effects such as DNA damage reagents and UV irradiation.The sensors could provide an active,effective,and sensitive potential monitoring method for future evaluation of radiation effects in space.

Objective:To investigate the volume management of intermittent veno-venous hemofiltration (IVVH) guided by critical care ultrasound in the treatment of acute kidney injury (AKI) in patients with heart failure (HF).Methods:A total of 216 patients with HF and AKI treated with IVVH in the coronary care unit (CCU) of the Third Central Hospital of Tianjin from April 2019 to June 2022 were selected as the study subjects, the patients were randomly divided into conventional guidance group (107 cases) and ultrasound guidance group (109 cases). According to the recovery of renal function, IVVH was performed 12 hours every day or 12 hours every other day. The conventional guidance group selected the conventional method to formulate IVVH prescription, and the ultrasound guidance group used critical care ultrasound to adjust the treatment parameters of IVVH on the basis of the conventional guidance group. Respiratory variation index (RVI) of inferior vena cava (IVC), right left ventricular end-diastolic transverse area ratio, early diastolic peak mitral flow velocity/mitral annulus velocity peak (E/E'), aortic flow velocity time integral (VTI), cardiac output (CO), bilateral lung ultrasound B-line range, bilateral renal interlobar arteries resistance index (RI) were recorded before and 3, 6, 9 hours after each treatment. The net dehydration rate was adjusted in real time according to the comprehensive results. Urine volume, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), blood B-type brain natriuretic peptide (BNP), β 2-microglobulin (β 2-MG) and cystatin C (Cys C) levels of patients in both groups were monitored before and 3, 7 and 10 days after initial treatment, and renal function recovery and clinical prognostic indexes of patients in both groups were recorded. Results:The dehydration rate of the ultrasound guidance group was slow at the beginning of IVVH, and gradually increased after 6 hours, and the overall dehydration rate was significantly slower than that of the conventional guidance group. In the ultrasound guidance group using critical care ultrasound, the RVI gradually increased, the right left ventricular end-diastolic area ratio gradually decreased, the E/E' ratio gradually decreased, and the range of B-line of bilateral lungs gradually decreased, RI of bilateral renal interlobar arteries decreased. At 3, 7 and 10 days after the first IVVH, renal function related indexes in both groups were significantly improved compared with before treatment, and the decline rate of β 2-MG and Cys C in the ultrasound guidance group was faster than that in the conventional guidance group at early (3 days) [β 2-MG (mg/L): 3.69±1.31 vs. 3.99±1.45, Cys C (mg/L): 2.91±0.95 vs. 3.14±0.96, both P < 0.05], urine volume, SCr and eGFR at 7 days were also significantly improved compared with the conventional guidance group [24-hour urine volume (mL): 1 128.23±153.92 vs. 1 015.01±114.18, SCr (μmol/L): 145.86±32.25 vs. 155.64±28.42, eGFR (mL/min): 50.26±11.24 vs. 46.51±10.61, all P < 0.05]. The time of SCr recovery, the time of reaching polyuria, the total time of IVVH treatment, the time of non-invasive mechanical ventilation and the time of living in CCU in the ultrasound guidance group were shorter than those in the conventional guidance group. The incidences of hypotension, long-term RRT, incidence of major cardiovascular adverse event (MACE) and at 28-day mortality were all lower than those in the conventional guidance group. Kaplan-Meier survival curve showed that the 28-day cumulative survival rate in the ultrasound guidance group was significantly lower than that in the conventional guidance group (Log-Rank test: χ 2 = 3.903, P = 0.048). Conclusion:The strategy of IVVH guided by critical care ultrasound in the treatment of HF with AKI has unique advantages.

Objective : To investigate the effect of hypoxic preconditioning (HPC) on mitochondrial energy metabolism in mouse hippocampal HT22 cells and its possible mechanism. Methods : In this paper, mouse hippocampal nerve cells HT22 were divided into control group, hypoxia group, HPC group, and the levels of adenosine triphosphate (ATP) and reactive oxygen species (ROS) in each group were measured for observing the effect of HPC on cell mitochondrial metabolism. Western blot was used to detect the expression of target of rapamycin ( mTOR), phosphorylated mTOR protein and autophagy substrate P62 protein; cellular immunofluorescence was used to detect phosphorylated mTOR, and LysoTrackerTM probe was used to detect lysosomes. Results : Compared with the control group, the ATP level was significantly decreased and the ROS level was increased in the hypoxia group. Exposed to HPC, the ATP level was increased and the ROS level was decreased. Compared with the control group, the expression of phosphorylated mTOR was down⁃regulated and the expression of autophagy substrate P62 was down⁃regulated in the HPC group. Conclusion HPC may affect the energy metabolism of HT22 cells through the mTOR/autophagy signaling pathway, thereby exerting a protective effect on the HT22 cells.

Objective To investigate the regulation mechanism of dendrobium nobile polysaccharides (DNP) for nuclear factor kappa B (NF-κB) signal pathway in focal cerebral ischemia/reperfusion rats.Methods According to the digital random method,90 SD rats were divided into 6 groups:sham operation,model,DNP low-dose (DL,50 mg/kg),moderate-dose (DM,100 mg/kg) and high-dose (DH,200 mg/kg),and nimodipine (10 mg/kg) groups (n =15 in each group),and according to the random number method,selecting 5 in each group for the corresponding index detection.A focal cerebral ischemia/reperfusion model in SD rats was induced by middle cerebral artery occlusion.The improvement effect of DNP on rat neurological deficit (Bederson behavioral score) and brain water content,and infarct volume were observed.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of proinflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-β (IL-1 β) in brain tissue.Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect microglial cell marker BCL-2-related protein A1 α (A1) and astrocyte marker glial fibrillary acidic protein (GFAP) mRNA transcription levels.Western blot was used to detect the NF-κB signaling pathway phosphorylated IκBα protein and nuclear p65 protein expression levels.Single factor variance analysis was used to compare the measurement data among the groups.Results (1) There were significant differences in the neurological deficit score,brain water content,cerebral infarction volume,brain tissue TNF-α and IL-1β levels,A 1 and GFAP mRNA transcription levels and phosphorylated IκBα protein and nuclear p65 protein levels among the 6 groups (F =22.24,8.699,33.89,19.26,27.53,109.5,15.28,66.86,and 41.63,respectively (all P ＜ 0.01).(2) The neurological deficit score,cerebral water content,and cerebral infarction volume in the model group were 2.8 ± 0.3,86.1 ±3.8％,and 31.0 ±4.5％,respectively.The TNF-α and IL-1β levels,A1 and GFAP m RNA transcription levels in brain tissue,and phosphorylated IκBα protein and nuclear p65 protein levels were increased significantly compared with those in the sham operation group.There were significant differences (all P ＜0.01).(3)The above indices in the DH group were 1.5 ± 0.5,72.9 ±5.4％,and 17.5 ±4.1％,respectively.Compared with the model group (including TNF-α and IL-1 β levels,A1 and GFAP mRNA transcription levels and phosphorylation of IκBα protein and nuclear p65 protein levels in brain tissue).There were significant differences (all P ＜ 0.05).Compared with the nimodipine group,there were no significant differences (all P ＞ 0.05).Compared with the sham operation group,except for there were no significant difference in brain water content,phosphorylated IκBα protein and nuclear p65 protein (P ＞0.05),there were significant differences in other indices (all P ＜ 0.05).(4) Compared with the model group,only IL-1 β and phosphorylated IκBα protein levels were decreased significantly in the DM group,there were no significant differences in other indices (all P ＞ 0.05).Compared with the sham operation group,there were significant differences in other indices (all P ＜ 0.05).(5) Compared with the model group,there were no significant differences in other indices in the DL group (P ＞ 0.05).Compared with the sham operation group,there were significant differences in all indices (all P ＜ 0.05).Conclusion Highdose DNP may reduce focal cerebral ischemia/reperfusion injury in rats.The mechanism of may be associated with the inhibition of activation of early NF-κB signaling pathway.The effects of low-and moderate-dose DNP on reducing inflammatory brain damage of focal cerebral ischemia/reperfusion may be not obvious.