Objective To investigate the effects of long-term occupational exposure to high-frequency noise in specific frequency bands on auditory function of the inner ear,and to evaluate the mechanisms of auditory threshold damages due to high-frequency noise exposure utilizing bone conduction audiometry and acoustic physical models.Methods The study subjects included factory workers and airport ground staff working in high-noise environments for a long period.Two groups(an exposure group and a control group)were established,and the exposure group was further divided into 3 subgroups according to exposure duration:5-9 years,10-14 years,and over 15 years.Bone conduction audiometry was used to assess auditory threshold changes in different frequency bands(4,6,8 kHz),while a sound level meter was employed to record noise exposure intensity.The impact of noise on the cochlea was simulated using an acoustic physical model.Multivariable regression analysis,controlling for confounding factors such as age and gender,was used to further analyze the independent effects of exposure duration and intensity on auditory damage.Results The auditory thresholds of exposure group were significantly higher than those of control group in the high-frequency bands,particularly in 8 kHz frequency band(P＜0.001).With increasing exposure duration,auditory damage in exposure group progressively worsened,and the most significant auditory threshold changes was found in the group exposed for over 15 years.The predictions made by the acoustic physical model closely matched the actual measurements,and the high model fitting degree(R2:0.85-0.90)in the long-term exposure group indicated a strong predictive capability for the cumulative effects of cochlear damage.Conclusion Long-term exposure to high-frequency noise in specific frequency bands results in significant cumulative damage to auditory function of the inner ear.Exposure duration and intensity are the primary independent risk factors.

Panax ginseng(PG)and Panax notoginseng(PN)are highly valuable Chinese medicines(CM).Although both CMs have similar active constituents,their clinical applications are clearly different.Over the past decade,RNA sequencing(RNA-seq)analysis has been employed to investigate the molecular mechanisms of extracts or monomers.However,owing to the limited number of samples in standard RNA-seq,few studies have systematically compared the effects of PG and PN spanning multiple conditions at the transcriptomic level.Here,we developed an approach that simultaneously profiles transcriptome changes for multiplexed samples using RNA-seq(TCM-seq),a high-throughput,low-cost workflow to molecularly evaluate CM perturbations.A species-mixing experiment was conducted to illustrate the accuracy of sample multiplexing in TCM-seq.Transcriptomes from repeated samples were used to verify the robustness of TCM-seq.We then focused on the primary active components,Panax notoginseng sa-ponins(PNS)and Panax ginseng saponins(PGS)extracted from PN and PG,respectively.We also char-acterized the transcriptome changes of 10 cell lines,treated with four different doses of PNS and PGS,using TCM-seq to compare the differences in their perturbing effects on genes,functional pathways,gene modules,and molecular networks.The results of transcriptional data analysis showed that the tran-scriptional patterns of various cell lines were significantly distinct.PGS exhibited a stronger regulatory effect on genes involved in cardiovascular disease,whereas PNS resulted in a greater coagulation effect on vascular endothelial cells.This study proposes a paradigm to comprehensively explore the differences in mechanisms of action between CMs based on transcriptome readouts.

Chronic hepatitis B virus (HBV) infection is the main cause of viral hepatitis, liver cirrhosis, and primary liver cancer. At present, nucleos(t)ide analogues (NUC) and pegylated interferon α used in clinical practice cannot directly target covalently closed circular DNA, and it is difficult to achieve clinical cure of chronic hepatitis B patients; therefore, it is urgently needed to develop direct-acting antiviral agents targeting all stages of the HBV replication cycle. Capsid assembly modulator (CpAM) targets the assembly of viral capsids through various mechanisms, thereby exerting a direct-acting antiviral effect. Its combination with NUC should have a good synergistic antiviral effect, but the results of existing clinical trials have shown that chronic hepatitis B patients who received a limited course of antiviral therapy with CpAM and NUC all experienced off-therapy viral rebound. Based on the mechanism of action of these two types of drugs, this article provides a reasonable explanation for the above clinical trial results and points out that a longer course of antiviral therapy with CpAM and NUC may be needed in the future clinical trials with safe drug withdrawal as the end point of observation, so as to deplete or silence the pool of covalently closed circular DNA and increase the possibility of safe drug withdrawal in CHB patients. In addition, further studies are needed to explore antiviral therapeutic strategies with a combination of multiple targets.

Objective To investigate the immunomodulatory effect of pachymaran on cyclosporine A (CsA)-induced lung injury in mice. Methods (i) Fifty male BALB/c mice were randomly divided into five groups (10 mice in each group): normal control (NC) group, 30, 45, and 60 mg/kg CsA groups, and lipopolysaccharide (LPS) group. Except for the NC group, other groups underwent CsA modeling. The NC group was treated with phosphate-buffered saline (PBS), the LPS group with 10 mg/kg LPS eight hours before mice euthanized, and the 30, 45, and 60 mg/kg CsA groups with corresponding doses of CsA for seven consecutive days. After treatment, the body and organ mass of each group were weighed, and the lung, thymus, and spleen indexes were calculated. Hematoxylin-Eosin (HE) staining was performed to observe histopathological changes in the lungs of the mice. The protein expression levels of interleukin (IL)-2 and IL-1β in the blood were detected using enzyme-linked immunosorbent assay (ELISA), and those of surfactant protein D (SP-D), IL-2, and IL-6 in lung tissues were detected by immunohistochemistry (IHC). The mRNA expression levels of SP-D, IL-1β, IL-6, and myeloperoxidase (MPO) in the lung tissues were detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). (ii) Another 60 BALB/c mice were divided into six groups (10 mice in each group) : NC group, model control (MC) group, 50, 100, and 200 mg/kg pachymaran groups, and polyinosinic-polycytidylic acid [poly(I:C)] group. Except for the NC group, other groups underwent 45 mg/kg CsA modeling. The NC and MC groups were treated with distilled water, the pachymaran groups with corresponding doses pachymaran, and the poly(I:C) group with 0.1 mg/kg poly(I:C) for seven days.The mice were euthanized to obtain tissues and serum for detection. Detection methods were identical to those described in (i) above. Results (i) CsA (30 mg/kg) increased the lung index of mice (P < 0.001), and decreased the spleen index (P < 0.01), thymus index (P < 0.05), and the serum level of IL-2 (P < 0.05). CsA (45 mg/kg) decreased the spleen, thymus indexes, and the serum level of IL-2 (P < 0.01) in mice, and increased the serum level of IL-1β (P < 0.05) and the protein level of lung SP-D (P <0.001). CsA (60 mg/kg) increased the lung index of mice (P < 0.01), the serum level of IL-1β (P < 0.05), the protein level of lung SP-D (P < 0.01), and the mRNA levels of lung MPO and SP-D ( P < 0.05), and decreased the thymus index of mice (P < 0.01). HE staining showed that 30, 45, and 60 mg/kg CsA, and LPS caused pathological changes in the lung tissue of mice. (ii) After pachymaran intervention in MC mice, the spleen and thymus indexes (P < 0.05) were increased in the 100 and 200 mg/kg pachymaran groups, and the lung index was decreased (P < 0.05). Moreover, 50 mg/kg pachymaran increased the thymus index (P < 0.05) and decreased the lung index (P < 0.01) in MC group. Pachymaran (50, 100, and 200 mg/kg) improved lung tissue injury, reduced the serum level of IL-1β (P < 0.001), and the mRNA levels of MPO and SP-D in lung tissues (P < 0.05) of mice. Pachymaran (100 mg/kg) increased the protein level of lung IL-2 (P < 0.01), decreased the protein level of lung SP-D (P < 0.01), and the mRNA level of IL-1β (P < 0.001) in the lung tissues of mice. Pachymaran (200 mg/kg) increased the serum level of IL-2 (P < 0.01) and lung IL-6 of mice (P < 0.05). Pachymaran (50 and 200 mg/kg) increased the mRNA level of IL-6 in the lung tissues of mice (P < 0.05). Conclusion While the immune function of mice was suppressed by CsA, the lung tissue was also damaged. Pachymaran can improve the immunosuppression induced by CsA and improve the lung tissue injury in immunosuppressed mice.

Autoantibody-related congenital heart block (ACHB) is a passively acquired autoimmune disease developing in fetuses after exposuring to maternal anti-Ro/Sj?gren's syndrome type A (SSA) antibody and/or anti-La/SSB antibody transported across the placenta, which contributes to fetal heart conduction system damage and signal conduction block at the atrioventricular node. However, fetal atrioventricular block does not necessarily occur with the presence of maternal autoantibodies, indicating its complex pathogenesis. This review focuses on the theories of calcium channels and apoptosis, the influence of other maternal factors and environmental changes on ACHB and the roles of natural killer cells and human leukocyte antigen in ACHB, aiming to provide reference for further study on the pathogenesis.

Objective To explore whether inhibiting autophagy can enhance the sensitivity of photothermal treatment under mild photothermal conditions. Methods CQ@PLGA@PDA NPs were prepared by an improved double emulsification method and a PDA-based surface modification method. After basic characterization, CCK-8 method was used to detect the cytotoxicity of nanoparticles; the near-infrared laser irradiation nanoparticle solution was used to detect the heating effect; CCK-8 method and live-dead cell staining were used to detect the killing effect of tumor cells; Western blot was used to detect the expression of autophagy-related proteins. Results The CQ@PLGA@PDA NPs were successfully prepared, with a particle size of 253.10±2.39 nm, a zeta potential of -22.57±0.80 mV, uniform particle size and good dispersion. The temperature of nanoparticle solution increased to 45℃ after the near-infrared laser irradiation for 10 min. CQ@PLGA@PDA NPs had no obvious toxicity to cells. The survival rates of breast cancer cell MDA-MB-231 and mouse embryonic fibroblast NIH-3T3 cell were above 95%. The inhibition of autophagy under mild photothermal conditions could improve the sensitivity of photothermal therapy. Conclusion The prepared CQ@PLGA@PDA NPs have good photothermal performance and high biological safety; by inhibiting autophagy, they can effectively kill tumor cells under mild photothermal conditions(< 50℃).

Objective: To explore and analyze the possible mechanism of liver injury in patients with coronavirus disease 2019 (novel coronavirus pneumonia, NCP). Methods: The correlation between ALT, AST and other liver enzyme changes condition and NCP patients’ disease status reported in the literature was comprehensively analyzed. ACE2 expression in liver tissue for novel coronavirus was analyzed based on single cell sequencing (GSE115469) data. RNA-Seq method was used to analyze Ace2 expression and transcription factors related to its expression in liver tissues at various time-points after hepatectomy in mouse model of acute liver injury with partial hepatectomy. t-test or Spearman rank correlation analysis was used for statistical analysis. Results: ALT and AST were abnormally elevated in some patients with novel coronavirus infection, and the rate and extent of ALT and AST elevation in severe NCP patients were higher than those in non-severe patients. Liver tissue results of single cell sequencing and immunohistochemistry showed that ACE2 was only expressed in bile duct epithelial cells of normal liver tissues, and very low in hepatocytes. In a mouse model of acute liver injury with partial hepatectomy, Ace2 expression was down-regulated on the first day, but it was elevated up to twice of the normal level on the third day, and returned to normal level on seventh day when the liver recovered and hepatocyte proliferation stopped. Whether this phenomenon suggests that the bile duct epithelial cells with positive expression of Ace2 participate in the process of liver regeneration after partial hepatectomy deserves further study. In RNA-Seq data, 77 transcription factors were positively correlated with the expression of ACE2 (r > 0.2, FDR < 0.05), which were mainly enriched in the development, differentiation, morphogenesis and cell proliferation of glandular epithelial cells. Conclusion We assumed that in addition to the over activated inflammatory response in patients with NCP, the up-regulation of ACE2 expression in liver tissue caused by compensatory proliferation of hepatocytes derived from bile duct epithelial cells may also be the possible mechanism of liver tissue injury caused by 2019 novel coronavirus infection.

Objective In the recovery process of stroke patients, the ability of maintaining standing and sitting position might have a great effect on the improvement of activity of daily living. There are few the methods which evaluate quantitatively and effectively the ability of position control ability in clinical practice. The aim of the study is to quantitatively evaluate the reliability of posturographic parameters based on the center of pelvis in different standing positions and walking activity.Methods From May to June, 2018, Seventy-nine healthy participants were enrolled. They were evaluated with iReGo, a walking assisstant robot, in three conditions: normal standing position, left/right standing position and walking 10 meters at an appropriate speed. The computer calculated the posturographic parameters automatically. The participants completed their second test one day after the first one.Results During normal standing position, the intra-class correlation coefficients (ICC) of average sway in coronal plane, average sway in sagittal plane, path length, and covered area were more than 0.70. During left standing position, ICC of all the above parameters were more than 0.70. During right standing position, ICC of all the above parameters were more than 0.49. When walking 10 meters at an appropriate speed, ICC of path length and covered area were more than 0.75. Comparing different standing positions, the normal standing position was more stable than the left/right standing position, and there was no difference between the left and the right standing positions.Conclusion Posturographic parameters based on the center of pelvis might be a reliable way to assess the position control ability in different standing positions and walking process.

Objective Currently,the sit-to-stand process is not well evaluated.The aim of the study is to evaluate quantitatively the reliability of posturographic parameters in the sit-to-stand process.Methods Seventy-four healthy participants were enrolled and required to finish 20-second sitting,standing and the sit-to-stand process.The computer calculated the posturographic parameters automatically.The test was repeated twice to assess the reliability at an interval of six days.Results During sitting and standing position,the intraclass correlation coefficients (ICCs) of all the parameters were above 0.50,indicating a good or fair reliability.During the standing stance and sitting phase of the sit-to-stand process,the ICCs of all the parameters were above 0.40 and 0.60 respectively,showing a good or fair reliability.Conclusions Sit-to-stand posturographic parameters are a new way to assess the position control ability among the healthy participants with a good reliability.Further study should be conducted among patients to result in better functional and effectiveness evaluation.

Objective To report the anatomy basis and clinical application of the flap based on the perforator of plantar arch.Methods From December 2013 to June 2016,25 cadaveric feet which were injected with a mixture of red gelatin were used to observe:the origins,courses,branches,distributions of the dorsal perforators flap based on the plantar arch;the anastomoses between the back perforators of plantar arch and rete arteriosum of dorsale pedis.Based on the anatomy research,11 cases with soft tissue defect at forefoot were treated with the perforator flaps.Results 11 flaps survived completely with primary healing.The flaps were followed up for 2-36 months with good match of texture and color.Conclusions The flap based on the perforator of plantar arch has constant and rich blood supply.The technique is easily performed and can be used as an optional flap without major vessel for defect at forefoot.