Xihuangwan Inhibits Mitochondrial Energy Metabolism in Ovarian Cancer Cells / 中国实验方剂学杂志

ObjectiveTo study the effect of Xihuangwan extract on mitochondrial energy metabolism in ovarian cancer SKOV3 and HEY cells and to explore the underlying mechanism. MethodSKOV3 and HEY cells were cultured in vitro and treated with different concentrations （0， 5， 10， 15， 20 g·L-1） of Xihuangwan extract. Methyl thiazolyl tetrazolium （MTT） was used to examine the viability of SKOV3 and HEY cells treated with Xihuangwan extract. The adenosine-triphosphate （ATP） levels in SKOV3 and HEY cells were measured by kit. Flow cytometry was employed to measure the content of reactive oxygen species （ROS） in cells. Western blot was employed to determine the protein levels of peroxisome proliferator-activated receptor-γ co-activator 1α （PGC1α）， transcription factor A， mitochondrial （TFAM）， translocase of outer mitochondrial membrane 20 （TOMM20）， and aplasia Ras homologue member Ⅰ （ARHⅠ） in SKOV3 and HEY cells. Mito-Tracker Green staining was used to observe the morphological changes of mitochondria in SKOV3 and HEY cells. ResultCompared with blank group， Xihuangwan extract treatment for 24， 48 h inhibited the viability of SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）. Compared with blank group， Xihuangwan extract （10， 15， 20 g·L-1） groups presented lowered ATP levels （P<0.05， P<0.01）， and the 20 g·L-1 Xihuangwan extract group had lower ATP level than the 10 and 15 g·L-1 Xihuangwan extract groups （P<0.05）. Compared with blank group， Xihuangwan extract increased the content of ROS in SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）， and the 20 g·L-1 Xihuangwan extract group had higher ROS content than the 10 g·L-1 Xihuangwan extract group （P<0.05）. Compared with blank group， Xihuangwan extract up-regulated the expression level of ARHⅠ protein in SKOV3 and HEY cells in a concentration-dependent manner （P<0.01）， and the expression levels of ARHⅠ protein was higher in the 20 g·L-1 Xihuangwan extract group than in the 10 and 15 g·L-1 Xihuangwan extract groups （P<0.05）. Compared with the blank group， Xihuangwan extract down-regulated the protein levels of PGC1α， TFAM， and TOMM20 in SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）， and the protein levels of TFAM and TOMM20 in the HEY cells treated with 20 g·L-1 Xihuangwan extract were lower than those in the HEY cells treated with 10， 15 g·L-1 Xihuangwan extract （P<0.05）. Compared with the blank group， 20 g·L-1 Xihuangwan extract decreased the Mito-Tracker fluorescence intensity of SKOV3 and HEY cells （P<0.05）. ConclusionXihuangwan can compromise the mitochondrial function of ovarian cancer SKOV3 and HEY cells and reduce cell energy metabolism to inhibit the proliferation of SKOV3 and HEY cells by up-regulating ARHⅠ and inhibiting PGC1α/TFAM signaling axis.

A systematic review of the epidemiology and clinical characteristics of artificial stone-related silicosis and dust protection / 中华劳动卫生职业病杂志

Objective: To investigate the epidemiology, clinical characteristics, on-site dust monitoring and individual protection of the patients with artificial stone-related silicosis. Methods: In March 2022, the literature on artificial stone-related silicosis published from January 1965 to February 2022 was searched in China Journal Full-text Database, Wanfang Database, VIP Database, EMbase and PubMed. Chinese and English search terms include "silica dust""silica dust""silicosis""artificial stone""pneumoconiosis", etc. References were included according to inclusion and exclusion criteria, and data were extracted. The epidemiological characteristics, natural course of disease, workplace dust concentration and individual protection level of patients with artificial stone-related silicosis were analyzed by systematic review. Results: A total of 30 literatures were included, including 7 cohort studies, 14 cross-sectional studies, 3 case-control studies and 6 case reports. A total of 1358 patients with artificial stone-related silicosis were diagnosed from 1997 to 2020, with an average age of 41.5 years old and an average dust exposure time of 11.3 years. Among them, 36.2% (282/778) had progressive mass fibrosis or accelerated progressive silicosis at first diagnosis. Chest imaging showed diffuse small nodule shadow, pulmonary fibrosis, and silico-alveolar proteinosis. Pulmonary function showed restricted or mixed ventilation disorder with or without decreased diffusion volume. The disease progressed rapidly, with progressive mass fibrosis, respiratory failure, and even death. Patients engaged in artificial quartz stone processing, with high concentration of silica including ultra-fine particles, most of which were dry operation, lack of on-site ventilation measures and no effective personal protection. Conclusion: The artificial stone processing workers suffer from artificial stone-related silicosis due to dry cutting, lack of on-site dust removal facilities and personal protective measures, and the disease progresses rapidly, leading to poor prognosis.

Attach great importance to the significance of serum anti-müllerian hormone and androgen in the evaluation of polycystic ovary syndrome / 中华预防医学杂志

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of childbearing age, which seriously affects women's reproductive health. In recent years, more and more studies have found that serum anti-Müllerian hormone (AMH) has certain significance in the diagnosis and treatment evaluation of PCOS. In addition, with the improvement of detection methods, more attention has been paid to the significance of female androgens and AMH in the evaluation of PCOS. This article reviews the recent research progress of serum AMH and androgens in the evaluation of PCOS.

Effect of pirfenidone on paraquat-induced pulmonary fibrosis in rats / 中华劳动卫生职业病杂志

Objective: To construct paraquat (PQ) poisoning rat model and to explore the effect of pirfenidone (PFD) on PQ-induced pulmonary fibrosis. Methods: In April 2017, male 6-8 week-old Wistar rats were selected, and PQ was administered intraperitoneally at one time. PFD was administered by gavage 2 hours after poisoning. The daily gavage doses were 100, 200 and 300 mg/kg, and the rats were divided into physiological saline group, PQ group, PQ+PFD 100 group, PQ+PFD 200 group, PQ+PFD 300 group, with 10 rats in each group at each observation time point. The pathological changes of lung tissue at different time points (the 1st, 3rd, 7th, 14th, 28th, 42nd and 56th days) after poisoning and the effect of PFD intervention with different dose on PQ-induced pulmonary fibrosis were observed. Pathological evaluation of lung tissue was performed by Ashcroft scale method. The PQ+PFD 200 group was selected to further explore the pathological changes of lung tissue, the contents of hydroxyproline and malondialdehyde in lung tissue were determined.And the tumor necrosis factor (TNF) -α, interleukin (IL) -6, transforming growth factor (TGF) -β1, fibroblast growth factor (FGF) -B, platelet-derived growth factor (PDGF) -AB, insulin-like growth factor (IGF) -1 and PQ concentrations in serum and lung tissue were determined. Results: On the 1st to 7th day after PQ exposure, rats developed lung inflammation, which was aggravated on the 7th to 14th day, and pulmonary fibrosis appeared on the 14th to 56th day. Compared with PQ group, the Ashcroft scores of lung fibrosis in PQ+PFD 200 group and PQ+PDF 300 group decreased significantly in 7th and 28th day (P<0.05), while the Ashcroft score of lung fibrosis in PQ+PFD 100 group had no significant difference (P>0.05). After PQ exposure, the content of hydroxyproline in lung tissue increased gradually and reached the peak value on the 28th day. Compared with the PQ group, the contents of hydroxyproline in the PQ+PFD 200 group decreased at the 7th, 14th and 28th day, and the contents of malondialdehyde decreased at the 3rd and 7th day, the differences were statistically significant (P<0.05). The levels of TNF-α, IL-6 in rat serum and lung tissue reached the peak value on the 7th day after PQ exposure, and the levels of TGF-β1, FGF-B and IGF-1 in rat serum and lung tissue reached the peak value on the 14th day after PQ exposure, and the level of PDGF-AB in rat serum and lung tissue reached the peak value on the 28th day after PQ exposure. Compared with PQ group, the level of serum IL-6 in PQ+PFD 200 group decreased significantly on the 7th day, and serum TGF-β1, FGF-B, PDGF-AB and IGF-1 on the 14th and 28th day were decreased significantly (P<0.05). The levels of TNF-α, IL-6 in lung tissue of rats in PQ+PFD 200 group on the 7th day decreased significantly, and the levels of TGF-β1, FGF-B and IGF-1 in lung tissue of rats on the 14th day were significantly decreased, and the level of PDGF-AB in lung tissue of rats on the 28th day were significantly decreased (P<0.05) . Conclusion: PFD partially alleviates the PQ-induced lung inflammation and fibrosis by inhibiting oxidative stress, reducing the levels of pro-inflammatory and pro-fibrotic cytokines in serum and lung tissue, but does not affect the concentrations of PQ in serum and lung tissue.

A new lignan glucoside from stems and branches of Rhododendron ovatum / 中国中药杂志

Ten lignans were isolated from the ethanol extract of stems and branches of Rhododendron ovatum through column chromatography over silica gel, ODS, Sephadex LH-20, and MCI-gel resin and semi-preparative RP-HPLC. The structures of all compounds were elucidated by extensive spectroscopic data analysis(UV, IR, HR-ESI-MS, ECD and NMR) as(-)-4-epi-lyoniresinol-9'-O-α-L-rhamnopyranoside(1),(+)-lyoniresinol-3α-O-α-L-rhamnopyranoside(2),(+)-5'-methoxyisolariciresinol-9'-O-α-L-rhamnopyranoside(3),(-)-lyoniresinol-3α-O-β-D-glucopyranoside(4),(+)-lyoniresinol-3α-O-β-D-glucopyranoside(5),(-)-4-epi-lyoniresinol-9'-O-β-D-glucopyransoide(6), racemiside(7), neociwujiaphenol(8),(+)-syringaresinol(9), and homohesperitin(10). Among them, compound 1 was a new aryltetralin-type lignan. All the isolated lignans were tested for antioxidant activities in Fe~(2+)-cysteine induced rat liver microsomal lipid peroxidation in vitro, and compounds 8 and 9 showed antioxidant activities on the formation of malondiadehyde(MDA) in rat liver microsomes at 1×10~(-5) mol·L~(-1), with significant inhibitory rates of 75.20% and 91.12%, respectively.

Surveillance on dengue vector Aedes albopictus in Ningbo City in 2021 / 中国血吸虫病防治杂志

Objective To analyze the density, distribution and insecticide resistance of Aedes albopictus in Ningbo City in 2021, so as to provide insights into formulation of dengue fever control strategies. Methods Four administrative villages were randomly selected from each county (district) in Ningbo City from April to November, 2021, to investigate the indoor population density of Aedes larvae, and the Breteau index (BI) was calculated. The population density of adult mosquitoes was investigated in residential areas, parks/bamboo forests, waste tire stacking sites/waste stations/construction sites in each county (district). On June 2021, larvae of the natural strain A. albopictus were collected from epidemic sites of dengue fever in Ningbo City in 2018, and raised in laboratory. Then, larvae and female mosquitoes without blood feeding were selected for insecticide resistance bioassays, while insecticide-sensitive strains of A. albopictus served as controls. The resistance of A. albopictus larvae to deltamethrin, beta-cypermethrin, propoxur, temephos and dichlorvos using the impregnation method, and the medium lethal concentration (LC50) and resistance ratio (RR) were calculated. The resistance of adult A. albopictus to beta-cypermethrin, permethrin, deltamethrin, propoxur and malathion was determined using the tube bioassay, and the mosquito mortality was calculated. Results A total of 10 072 small water containers from 9 935 households were investigated in Ningbo City in 2021, and there were 1 276 containers with Aedes larvae detected, with an average BI of 12.89. Totally 1 422 mosquito nets were allocated and 954 female A. albopictus were captured, with an average net trapping index of 1.34 mosquitoes/(net·hour). Both larval and adult A. albopictus mosquitoes were found from April to November, and the density of larval A. albopictus peaked in September (BI = 21.21), while the density of adult A. albopictus peaked in August, with a net trapping index of 2.38 mosquitoes/(net·hour). The LC50 values of delta-methrin, beta-cypermethrin, propoxur, temephos and dichlorvos were 0.017 4, 0.000 9, 0.364 1, 0.038 1 mg/L and 0.001 6 mg/L against larvae of natural strains of A. albopicchus, with RRs of 49.66, 25.53, 9.65, 2.24 and 6.06, and the mortality rates of adult mosquitoes were 66.00% (66/100), 69.39% (68/98), 25.00% (25/100), 98.97% (96/97) and 100.00% (98/98) 24 hours post-treatment with 0.08% beta-cypermethrin, 0.03% deltamethrin, 0.4% permethrin, 0.05% propoxur, and 0.5% malathion for 24 h, respectively. Conclusions A. albopictus is widely distributed in Ningbo City, with a high population density and presents high-level resistance to common pyrethroid insecticides. The population density and insecticide resistance of A. albopictus requires to be reinforced.

Effects of non-muscle myosin Ⅱ silenced bone marrow-derived mesenchymal stem cells transplantation on lung extracellular matrix in rats after endotoxin/lipopolysaccharide-induced acute lung injury / 中华烧伤杂志

Objective: To investigate the effects of non-muscle myosin Ⅱ (NMⅡ) gene silenced bone marrow-derived mesenchymal stem cells (BMMSCs) on pulmonary extracellular matrix (ECM) and fibrosis in rats with acute lung injury (ALI) induced by endotoxin/lipopolysaccharide (LPS). Methods: The experimental research methods were adopted. Cells from femur and tibial bone marrow cavity of four one-week-old male Sprague-Dawley rats were identified as BMMSCs by flow cytometry, and the third passage of BMMSCs were used in the following experiments. The cells were divided into NMⅡ silenced group transfected with pHBLV-U6-ZsGreen-Puro plasmid containing small interference RNA sequence of NMⅡ gene, vector group transfected with empty plasmid, and blank control group without any treatment, and the protein expression of NMⅡ at 72 h after intervention was detected by Western blotting (n=3). The morphology of cells was observed by an inverted phase contrast microscope and cells labeled with chloromethylbenzoine (CM-DiⅠ) in vitro were observed by an inverted fluorescence microscope. Twenty 4-week-old male Sprague-Dawley rats were divided into blank control group, ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group according to the random number table, with 5 rats in each group. Rats in blank control group were not treated, and rats in the other 3 groups were given LPS to induce ALI. Immediately after modeling, rats in ALI alone group were injected with 1 mL normal saline via tail vein, rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were injected with 1×107/mL BMMSCs and NMⅡ gene silenced BMMSCs of 1 mL labelled with CM-DiⅠ via tail vein, and rats in blank control group were injected with 1 mL normal saline via tail vein at the same time point, respectively. At 24 h after intervention, the lung tissue was collected to observe intrapulmonary homing of the BMMSCs by an inverted fluorescence microscope. Lung tissue was collected at 24 h, in 1 week, and in 2 weeks after intervention to observe pulmonary inflammation by hematoxylin eosin staining and to observe pulmonary fibrosis by Masson staining, and the pulmonary fibrosis in 2 weeks after intervention was scored by modified Ashcroft score (n=5). The content of α-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and MMP-9 was detected by immunohistochemistry in 2 weeks after intervention (n=3), the activity of superoxide dismutase (SOD), malondialdehyde, myeloperoxidase (MPO) was detected by enzyme-linked immunosorbent assay at 24 h after intervention (n=3), and the protein expressions of CD11b and epidermal growth factor like module containing mucin like hormone receptor 1 (EMR1) in 1 week after intervention were detected by immunofluorescence staining (n=3). Data were statistically analyzed with one-way analysis of variance, Bonferroni method, and Kruskal-Wallis H test. Results: At 72 h after intervention, the NMⅡprotein expression of cells in NMⅡ silenced group was significantly lower than those in blank control group and vector group (with P values <0.01). BMMSCs were in long spindle shape and grew in cluster shaped like vortexes, which were labelled with CM-DiⅠ successfully in vitro. At 24 h after intervention, cell homing in lung of rats in ALI+NMⅡ silenced BMMSC group was more pronounced than that in ALI+BMMSC group, while no CM-DiⅠ-labelled BMMSCs were observed in lung of rats in blank control group and ALI alone group. There was no obvious inflammatory cell infiltration in lung tissue of rats in blank control group at all time points, while inflammatory cell infiltration in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly less than that in ALI alone group at 24 h after intervention, and alveolar wall turned to be thinner and a small amount of congestion in local lung tissue appeared in rats of the two groups in 1 week and 2 weeks after intervention. In 1 week and 2 weeks after intervention, collagen fiber deposition in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group was significantly aggravated compared with that in blank control group, while collagen fiber deposition in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly improved compared with that in ALI alone group. In 2 weeks after intervention, modified Ashcroft scores for pulmonary fibrosis of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were 2.36±0.22, 1.62±0.16, 1.06±0.26, respectively, significantly higher than 0.30±0.21 in blank control group (P<0.01). Modified Ashcroft scores for pulmonary fibrosis of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly lower than that in ALI alone group (P<0.01), and modified Ashcroft score for pulmonary fibrosis of rats in ALI+NMⅡ silenced BMMSC group was significantly lower than that in ALI+BMMSC group (P<0.01). In 2 weeks after intervention, the content of α-SMA in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly decreased compared with that in ALI alone group (P<0.05 or P<0.01). The content of MMP-2 in lung tissue of rats in the 4 groups was similar (P>0.05). The content of MMP-9 in lung tissue of rats in ALI alone group was significantly increased compared with that in blank control group (P<0.01), and the content of MMP-9 in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01). At 24 h after intervention, the activity of malondialdehyde, SOD, and MPO in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in blank control group (P<0.01), the activity of malondialdehyde in lung tissue of rats in ALI+NMⅡ silenced BMMSC group and the activity of SOD in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in ALI alone group (P<0.05 or P<0.01), and the activity of SOD in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). The activity of MPO in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01), and the activity of MPO in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). In 1 week after intervention, the protein expression of CD11b in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly increased compared with those in the other three groups (P<0.05 or P<0.01), while the protein expressions of EMR1 in lung tissue of rats in the four groups were similar (P>0.05). Conclusions: Transplantation of NMⅡ gene silenced BMMSCs can significantly improve the activity of ECM components in the lung tissue in LPS-induced ALI rats, remodel its integrity, and enhance its antioxidant capacity, and alleviate lung injury and pulmonary fibrosis.

Correlation of serum lipids levels of Alzheimer's disease patients with sex, age and apolipoprotein E gene polymorphism / 中华预防医学杂志

Objective: To explore the correlation of serum lipids levels of Alzheimer's disease (AD) patients with sex, age and apolipoprotein E (Apo E) gene polymorphism. Methods: The retrospective study method was used, and 407 AD patients (142 males and 265 females, aged 52-91 years) were selected from Beijing Tiantan Hospital from January 2015 to August 2021 as the research target, and 894 healthy persons (339 males and 555 females, aged 52-94 years) who did body examination were selected as the control group. The AD patients were divided into four age groups according to the age interval of 10 years, including 85 aged 50-59 years, 163 aged 60-69 years, 119 aged 70-79 years, and 40 aged more than 80 years. The serum lipids levels were detected by biochemical analyzer, including triglycerides (TG), cholesterol (CHO), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoproteinA1(Apo A1) and apolipoprotein B (Apo B). ApoE gene polymorphism were detected by PCR fluorescent probe method. Mann-Whitney U test and Kruskal-Wallis H test were used to compare the serum lipids levels in each group. Results: The levels of serum CHO and LDL-C were 3.30(1.41,4.82) mmol/L and 1.76(1.39,2.78) mmol/L in AD patients, and 4.84(4.24, 5.56) mmol/L and 2.91(2.36, 3.57) mmol/L in control group, and the levels of serum CHO and LDL-C of AD patients were significantly lower than control group (Z=-15.172,Z=-14.583 , P<0.001, P<0.001). The levels of serum HDL-C and Apo B were 1.84(1.30, 3.88) mmol/L and 1.17(0.85, 1.57) g/L in AD patients, and 1.39(1.18, 1.64) mmol/L and 0.93(0.81, 1.09) g/L in control group, and the levels of serum HDL-C and Apo-B of AD patients were significantly higher than control group (Z=-12.249 , Z=-9.706 , P<0.001, P<0.001). There was no significant difference in TG and Apo A1 between 2 groups (Z=-1.577 , Z=-0.408 , P=0.115, P=0.683). The levels of TG, CHO, LDL-C in female AD patients were significantly higher than male patients (Z=-2.737 , Z=-3.963 , Z=-4.417, P=0.006, P<0.001, P<0.001). There were significant differences in TG, CHO, HDL-C, LDL-C, Apo A1 and Apo B among AD patients of all age groups (Z=11.263 , Z=10.060 , Z=40.246 , Z=10.451 , Z=24.315 , Z=19.922 , P=0.010 , P=0.018 , P<0.001 , P=0.015 , P<0.001 , P<0.001). The serum CHO and LDL-C levels were positively correlated with age (rs=0.160, rs=0.174, P=0.001, P<0.001), and HDL-C, Apo A1 and Apo B levels were negatively correlated with age (rs=-0.312, rs=-0.272, rs=-0.146, P<0.001, P<0.001, P=0.003), and there was no correlation between TG level and age in AD patients (rs=0.086, P=0.082). There were 3 cases (3.33%) of E2, 43 cases of E3 (47.78%) and 44 cases of E4 (48.89%) in AD patients, and 22 cases (12.72%) of E2, 117 cases of E3 (67.63%) and 34 cases of E4 (19.65%) in control group. There was significant difference in Apo E genotype distribution between AD patients and control group (χ²=26.381 , P<0.001). Apo E4 was the most common genotype in AD patients, and the proportion was 48.89%. Except for Apo A1(Z=7.821 , P=0.020), there was no significant difference in TG, CHO, HDL-C, LDL-C and Apo B levels among all patients with different genotypes (Z=3.732 , Z=1.677 , Z=1.455 , Z=1.619 , Z=2.202 , P=0.155, P=0.432, P=0.483, P=0.445, P=0.333). Conclusion: The levels of CHO and LDL-C decreased while the levels of HDL-C and Apo B increased in AD patients. The dyslipidemia in AD patients might be correlated with age, but not sex and Apo E genotypes.

The realization modes of non-coplanar radiotherapy technology / 中华放射肿瘤学杂志

Non-coplanar radiotherapy is a kind of radiotherapy technology which employs multiple non-coplanar fixed fields or non-coplanar arcs. The non-coplanar field can be defined that the central axis of each field is not on the same plane, while the non-coplanar arc can be described that the trajectory formed by each arc is not on the same plane. Compared with coplanar radiotherapy, non-coplanar radiotherapy can achieve multi-angle or multi-radian irradiation, which effectively improves the focusing level of ray and is beneficial to enlarge the radiation dose of the target area between the surrounding normal tissues. Its dosimetric advantages have been proven in multiple types of tumors, such as intracranial tumors, liver cancer and lung cancer, etc. Multiple approaches can be employed to realize non-coplanar radiotherapy, which can be divided into the non-coplanar conic radiotherapy, non-coplanar conformal radiotherapy, non-coplanar intensity-modulated radiotherapy and non-coplanar volumetric modulated arc therapy according to the established sequence. In this review, the development process and principal characteristics of these implementations were summarized.

Dosimetric comparison between conventional IMRT and EBCRT combined with IMRT for post-mastectomy left-sided breast cancer patients / 中华放射医学与防护杂志

Objective:To investigate the dosimetric differences between conventional IMRT and electron beam conformal radiotherapy (EBCRT) combined with IMRT for post-mastectomy left-sided breast cancer patients.Methods:A total of 20 post-mastectomy left-sided breast cancer patients who were treated in the Ningbo First Hospital from June 2018 to October 2021 were retrospectively studied. The planning target volume (PTV) included the supra-and infra-clavicular regions(PTV sc)and the ipsilateral chest wall (PTV cw), and the prescribed dose was 50 Gy/25 f. All radiotherapy plans were designed using the Varian Eclipse treatment planning system (TPS). After that, the dose distribution of the target volume and the dose exposure of organs at risk (OARs) were compared and analyzed. Results:All the IMRT plans met the clinical requirements, yet 2/20 of the EBCRT combined with IMRT plans were not clinically accepted. For these two patients, the maximum chest wall thickness was 3.7 cm and 4.4 cm each, and the designed electron beam energy was 12 MeV and 15 MeV, respectively. The dose to the ipsilateral lung of these two patients exceeded the institution-specific dose limit standard. For the remaining 18 patients whose chest wall thickness was 3 cm or less, the designed electron beams were 9 MeV or less. All the EBCRT combined with IMRT plans were clinically accepted. The target dose distribution of the conventional IMRT was better than that of the EBCRT combined with IMRT (uniformity index (HI): PTV sc: t = -10.20, P<0.05; PTV cw: t = -9.24, P<0.05; conformal index (CI): PTV all: t = 10.39, P <0.05). For OARs, the V5 Gy, V20 Gy, and Dmean of the ipsilateral lung of EBCRT combined with IMRT were lower than those of IMRT ( t = 5.98, 6.30, 11.30, P <0.05). Specifically, the V25 Gy and Dmean of heart decreased by 8.3% and 4.79 Gy, respectively ( t = 15.23, 15.76, P<0.05), the Dmean of the left anterior descending coronary artery (LADCA) decreased by 44.03% ( t = 11.69, P <0.05), and the V5 Gy and Dmean of the contralateral breast decreased by 7.9% and 0.8 Gy, respectively ( t = 3.66, 4.93, P<0.05). The dosimetric differences of other OARs were not statistically significant ( P > 0.05). Conclusions:For post-mastectomy left-sided breast cancer patients with a chest wall thickness of less than 3 cm, EBCRT combined IMRT can significantly reduce the exposure dose to the heart, the ipsilateral lung, and the contralateral breast, which is beneficial to reducing the potential risk of long-term complications after radiotherapy and can further improve the long-term overall survival rate of patients. For patients with thick chest wall, IMRT plans are more technologically ideal.

The long-term efficacy of left cardiac sympathetic denervation in long QT syndrome / 中华心血管病杂志

Objective: To investigate the long-term efficacy and safety of left cardiac sympathetic denervation(LCSD) for long QT syndrome(LQTS) patients with either recurrence on drug therapy intolerance/refusal. Methods: This study was a retrospective cohort study. The cases selected from 193 patients with LQTS who were enrolled in the Chinese Channelopathy Registry Study from November 1999 to November 2012. This study selected 28 LQTS patients with either recurrence on drug therapy intolerance/refusal and underwent LCSD surgery in the Peking University People's Hospital or Beijing Tongren Hospital. The patients were allocated into 3 groups: high-risk group(n=13, baseline QTc ≥550 ms or symptomatic in the first year of life or highly malignant genetics); intermediate-risk group(n=10, 500 ms≤baseline QTc<550 ms, symptomatic after the first year and without highly malignant genetics); low-risk group(n=5, baseline QTc<500 ms, symptomatic after the first year and without highly malignant genetics). LCSD was performed with the traditional supraclavicular approach or video assisted thoracoscopic surgery (VATS). Patients were regularly followed up until 20 years after the surgery. Data were collected before and 1 year after surgery and at the last follow-up. Patients' electrocardiograph(ECG), cardiac events and surgery-related complications were recorded. Kaplan-Meier survival analysis was used to determine the cardiac event-free survival based on different risk stratification and genotypes. Results: A total of 28 LQTS patients, aged 20.5 (15.0, 37.5) and underwent LCSD surgery, were enrolled in this study, including 23(82.1%) women. There were 11(39.3%) patients treated with traditional approach while 17(60.7%) with VATS-LCSD. There were 19(67.9%) patients had positive genetic test results, including 4 LQT1, 12 LQT2, 1 LQT1/LQT2 mixed type, and 2 Jervell-Lange-Nielsen (JLN) syndrome. The median follow-up period was 189.3(138.7, 204.9) months. The dropout rate was 10.7%(3/28) while 3 patients in the intermediate-risk group were lost to follow-up. Horner syndrome occurred in 1 patient (in the high-risk group). Sudden cardiac deaths were observed in 3 (12.0%) patients (all in the high-risk group), and 12 patients (48.0%) had syncope recurrences (2 in low-risk group, 3 in intermediate-risk group and 7 in high-risk group). A significant reduction in the mean yearly episodes of cardiac events was observed, from (3.5±3.3) before LCSD to(0.2±0.1) at one year after LCSD and (0.5±0.8) at last follow up(P<0.001). The mean QTc was shortened from (545.7±51.2)ms before the surgery to (489.0±40.1)ms at the last follow-up (P<0.001). Among the 20 patients with basic QTc ≥500 ms and completing the follow-up, the QTc intervals of 11(55.0%) patients were shortened to below 500 ms. The event free survival rates for any cardiac events after LCSD decreased sequentially in the low-, intermediate- and high-risk groups, and the difference was statistically significant (χ²=7.24, log-rank P=0.026). No difference was found in the event free survival rates among LQT1, LQT2 and undefined gene patients (χ²=5.20, log-rank P>0.05). Conclusions: LCSD surgery can reduce the incidence of cardiac events and shorten the QTc interval in patients with LQTS after the long-term follow-up. LCSD surgery is effective and safe for patients with LQTS ineffective or intolerant to drug therapy. However, high-risk patients are still at a high risk of sudden death after surgery and should be actively monitored and protected by combined therapies.

K-115 enhances autophagic activity and attenuates TGF-β1-induced activation of human Tenon's fibroblasts / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the influence of K-115 on the proliferation and migration of human Tenon's fibroblasts(HTFs)and to access the possible mechanism. Furthermore, to provide new ideas for anti-scar treatment after glaucoma surgery.METHODS: The Tenon capsule tissues were collected from patients who underwent glaucoma surgery in Hebei General Hospital from September 2018 to September 2019. Primary culture of HTFs was performed by tissue block method. The transforming growth factor-β1(TGF-β1)was used to induce HTFs activation that can mimic glaucoma filtration surgery. The cells were treated with K-115 and divided into 4 groups: the control group was treated with dimethyl sulfoxide(DMSO); TGF-β1 group was treated with 10μg/L TGF-β1 for 24h; TGF-β1 +5 K-115 group was pretreated with 5μmol/L K-115 for 2h and then treated with 10μg/L TGF-β1 for 24h; TGF-β1+10 K-115 group was pretreated with 10μmol/L K-115 for 2h and then 10μg/L TGF-β1 was added for 24h. Cell proliferation was observed by cell proliferation experiment. The migration ability of cells was detected by scratch test. The formation of autophagosomes was observed by transmission electron microscopy. Apoptosis was visualized by Hoechst 33342/PI staining.RESULTS: Cell proliferation experiment revealed that K-115 could inhibit the proliferation of HTFs induced by TGF-β1. Scratch test suggested that K-115 could inhibit the migration of HTFs induced by TGF-β1. Transmission electron microscope results showed that K-115 could enhance autophagy of HTFs induced by TGF-β1. Hoechst 33342/PI staining suggested that K-115 did not induce apoptosis.CONCLUSIONS: K-115 may regulate the proliferation and migration of HTFs induced by TGF-β1 by increasing autophagy rather than inducing apoptosis.

Comparison of three fixed-field IMRT plans for nasal cavity and paranasal sinus tumors / 中华放射医学与防护杂志

Objective:To compare three fixed-field intensity-modulated radiotherapy (IMRT) plans for nasal cavity and paranasal sinus tumors, including the coplanar IMRT (C-IMRT) plan and the non-coplanar IMRT(NC-IMRT) plan which were based on a conventional C-arm LINAC (Trilogy), and the coplanar IMRT (H-IMRT) plan based on an O-ring LINAC (Halcyon).Methods:Based on the data of 10 patients in the Ningbo First Hospital from December 2018 to December 2021 with nasal cavity and paranasal sinus tumors who underwent postoperative radiotherapy, this study redesigned three IMRT plans with the same prescribed doses and optimization objectives. Then, this study compared the doses of target volumes and organ at risks(OARs), the validation pass rates, and the execution time of these plans. Friedman test was employed in this study, and multiple comparisons were further made in cases of different results.Results:The differences in the conformal index (CI) of PTV and PTV boost of the three plans were statistically significant ( χ2 = 7.51, 9.69, P < 0.05). The multiple comparisons showed that the median CI of the H-IMRT plan was higher than that of the NC-IMRT plan ( Z = 2.53, 2.68, P < 0.05). The differences in other parameters of target volumes were not statistically significant. Compared with the C-IMRT plan, the H-IMRT plan reduced the Dmax of bilateral lenses, bilateral corneas, ipsilateral optic nerve, and ipsilateral eyeball ( Z = 2.80, 2.80, 2.80, 2.80, 2.81, 2.09, P < 0.05). Compared with the C-IMRT plan, the NC-IMRT reduced the Dmax of bilateral lenses, corneas, and eyeballs and contralateral optic nerve ( Z = 2.80, 2.66, 2.80, 2.70, 2.29, 2.29, 2.65, P < 0.05) and reduced the Dmean of bilateral eyeballs ( Z = 2.80, 2.80, P < 0.05). Compared with the NC-IMRT plan, the H-IMRT plan reduced the Dmax of the ipsilateral lens and cornea ( Z = 2.50, 2.08, P < 0.05), but increased the Dmax of the contralateral optic nerve and the Dmean of bilateral eyeballs ( Z = 2.80, 2.80, 2.80, P < 0.05). The validation pass rate of the three plans met the institutional standards, and the differences were not statistically significant. Moreover, the H-IMRT plan had the shortest median execution time (172.00 s), followed by the C-IMRT plan (337.50 s), and the NC-IMRT plan (388.00 s). Conclusions:The verification pass rate of the three plans can achieve the requirements of treatment implementation. The three plans had similar dosimetric differences in target volumes. However, the H-IMRT and NC-IMRT plans can protect the normal tissues (especially optical organs) more effectively than the C-IMRT plan, which is conducive to reducing the toxicity after radiotherapy and provides space for local dose increase or the radiotherapy for the treatment of tumor recurrence. The execution efficiency of the three plans is in the order of H-IMRT > C-IMRT > NC-IMRT. It is necessary to select appropriate radiotherapy equipment and technology according to actual situations.

Controversy and prospect of transanal total mesorectal excision / 中华胃肠外科杂志

As a novel surgical technique, taTME has developed rapidly in recent years. TaTME inevitably attracts some skepticism on safety, efficacy, and indication. First, the controversies over taTME are mainly reflected on the safety and effectiveness of taTME. On one hand, the increase of surgical complications, such as urethral injury, CO2 embolism, anastomotic leakage and pelvic infection, has raised concerns about the safety of taTME. Second, the poor quality of taTME specimens, the increased local recurrence rate and the impaired anal function after taTME, also make people question the effectiveness of taTME. Third, there are more or less controversies in the selection of taTME cases, surgical procedures and cost-effectiveness. However, it can not be denied that taTME has a promising future in view of both surgical theory and clinical practice. Furthermore, taTME is a relatively safe and effective supplementary surgical procedure, especially for patients with low rectal cancer. We should attach more importance to structured training for beginners and conduct high-quality clinical studies in the future development of taTME in China, so as to ensure the safe implementation of taTME and obtain high-level evidence-based medicine evidence, and then standardize the clinical practice of taTME.

Tolerance and dosimetric study of multi-leaf collimator leaf position accuracy for dynamic intensity-modulated radiotherapy / 中华放射肿瘤学杂志

Objective:To evaluate the dosimetric effect of multi-leaf collimator (MLC) position error on dynamic intensity-modulated radiotherapy (dMLC-IMRT), aiming to provide guidance for the establishment of MLC quality control accuracy and operation tolerance.Methods:In the phantom study, the virtual water phantom established in the treatment planning system (TPS), and three dynamic sliding window test fields with gap width of 5 mm, 10 mm and 20 mm were designed. Clinical treatment plans of 7 common tumor types were extracted, including nasopharyngeal carcinoma, glioma, lung cancer, esophageal cancer, cervical cancer, prostate cancer, and breast cancer, with 6 cases in each. MLC errors were introduced into the copy from original plan to generate the simulation plans. MLC errors included systematic open/close error, systematic deviation error and random error. The dosimetric differences between the original and simulation plans were compared.Results:The phantom study showed that the symbol of dose deviation was the same as that of systematic open/close error, and the value was increased with the increase of MLC error and decreased with the increase of gap width. The results of patient study showed that the systematic open/close error had a significant effect on dosimetry, the target volume dose sensitivities of different plans were 7.258-13.743%/mm, and were negatively correlated with the average field width. The dosimetric deviation caused by the systematic shift error below 2 mm was less than 2%. The dosimetric change caused by the random error below 2 mm could be neglected in clinical treatment.Conclusions:The minimal gap width should be limited in TPS, whereas the quality control of MLC should be strengthened. In addition, for the dynamic intensity-modulated treatment technology, 2 mm random error was suggested to be the operation tolerance during treatment delivery, and 0.2 mm alignment accuracy on each side (or 0.4 mm unilateral) is recommended to be the MLC quality control accuracy to ensure the dose accuracy of radiotherapy for different tumors.

Design of a drum-shaped applicator through Monte Carlo simulation for breast intraoperative radiotherapy / 中华放射肿瘤学杂志

Objective:To design a drum-shaped applicator through Monte Carlo simulation for breast intraoperative radiotherapy.Methods:Applicator designing process is as follows: first, determined the shape of the applicator based on the geometric characteristics of the breast tumor bed closed to the chest wall; second, calculated the scattering angle and dose rate of the electron beam after passing through a series of scattering foils of different thicknesses to determine the thickness of the scattering foil; thrid, modeled the layer according to the applicator′s geometric characteristics where modulator located, and designed the modulator through the relationship between the geometric characteristics of the layer and the surface dose of the applicator. EGSnrc/BEAMnrc and EGS4/DOSXYZ were employed to model the head of the Mobetron, the layer, the applicator, and to calculate the dose distributions.Results:The applicator has two components. The upper component is a 3cm-diametre cylindrical collimator with 0.5cm wall made of 0.3cm steel and 0.2cm water equivalent material (WEM), a 0.13cm-foil made of tansgen. The lower component is a 4cm-diametre drum made of 0.2cm WEM and a 0.14cm maximum thickness hill-shaped modulator made of steel. When the energy of electron beam was 12MeV, the dose rate was about 90.44 cGy/min, and the depth of the 50% isodose curve was 1cm.Conclusion:The applicator is successfully designed, and can obtain a drum-shaped dose distribution.

The current situation and influencing factors of occupational stress among undergraduate interns / 中华医学教育探索杂志

Objective:To investigate the status of occupational stress and its influencing factors among undergraduate interns.Methods:Three hundred and seventeen interns in Subei People's Hospital of Jiangsu Province were collected as research objects. In this study, the Job Content Questionnaire (JCQ), Effort-Reward Imbalance (ERI) Questionnaire and self-compiled general information questionnaire were used to evaluate the status of occupational stress and its influencing factors, and the regression analysis was carried out.Results:The results showed that 101 (31.9%) and 115 (36.3%) undergraduate interns were in significantly higher level occupational stress according to the JCQ and the ERI questionnaire respectively. Logistic regression analysis showed that the risk factors of the included occupational stress included the planning of further studies, more than 40 hours per week for internship, high score of intrinsic engagement and low score of social support. Exercise of more than three times a week was a protective factor for interns' occupational stress.Conclusion:The occupational stress of the undergraduate interns is at a high level and affected by many factors. Schools and hospitals should provide targeted mental health education for interns and improve relevant management policies.

Impact of proximal femoral shape on leg length discrepancy after total hip arthroplasty / 中国骨伤

OBJECTIVE@#To investigate the effect of different proximal femoral shapes on leg length discrepancy(LLD) after total hip arthroplasty(THA).@*METHODS@#Total 131 patients with osteoarthritis or osteonecrosis received unilateral biological total hip arthroplasty from June 2013 to June 2019. All patients' age, sex, side and pelvis anteroposterior digital radiography were retraspectively analyzed. There were 69 males and 62 females, 57 cases of left hip and 74 cases of right hip. The age ranges from 25 to 89 with an average age of 62 years. There were 48 cases of osteoarthritis and 83 cases of osteonecrosis. In this study, femoral cortical index (FCI) was used as the classification of proximal femoral shape, and bilateral lower limb length differences were measured by preoperative and postoperative pelvis anteroposterior digital radiography. Grouping according to FCI:> 0.6 was Dorr A group, 0.5 to 0.6 was Dorr B group, 0.6, the postoperative LLD was 6.30 mm (IQR 1.00 to 10.95 mm). When FCI was 0.5 to 0.6, the postoperative LLD was 5.85 mm(IQR-0.55 to 8.90 mm). FCI<0.5, the postoperative LLD was 1.95 mm(IQR -2.50 to 6.68 mm). LLD comparison of different proximal femoral shape was statistically significant (@*CONCLUSION@#High FCI increases the risk of lower extremity prolongation after surgery on the affectedside, while low FCI reduces the risk of lower extremity prolongation after surgery on the affected side. The surgeon can assess the shape of the proximal femur of the patient preoperatively and inform the patient in advance of possible changes in leg length of both lower extremities after total hip replacement.

Potential targets of Euodiae Fructus in treatment of insomnia based on network pharmacology / 中国中药杂志

The acupoint application of Euodiae Fructus at Yongquan(KI1) can significantly improve the sleep quality of patients with insomnia with berberine as the main effective component for the efficacy. Nineteen active compounds and 203 drug targets were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). After comparison with GeneCards and Online Mendelian Inheritance in Man(OMIM), 24 common genes of diseases and drugs were obtained. STRING 11.0 was used to construct a protein-protein interaction(PPI) network of the overlapping genes, and Matthews correlation coefficient(MCC) was employed to screen the core genes, which were then subjected to enrichment analysis with gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG). The results revealed that the main compounds of Euodiae Fructus, such as berberine and rutaecarpine, participated in the biological processes(such as neurotransmitter receptor activity) by regulating C-reactive protein(CRP), estrogen receptor 1(ESR1), 5-hydroxytryptamine(5-HT) receptor, and interleukin-6(IL-6) to exert sedative, anxiolytic, and antidepressant effects. Sixty 4-week-old SPF mice were randomly divided into a control group, a model group, a positive drug(diazepam tablets) group, and low-, medium-, and high-dose berberine groups. Medication with corresponding drugs was performed for one week. The results demonstrated that berberine was potent in reducing the activities and standing times of mice, down-regulating the levels of CRP and IL-6 mRNA in the hypothalamus, and up-regulating the expression of 5-HT(P<0.01); however, no significant effect on ESR1 was observed. The network of Euodiae Fructus in treating insomnia was constructed by network pharmacology and verified by tests. The findings indicated that the therapeutic efficacy of Euodiae Fructus in treating insomnia was achieved by participating in multiple biological processes, such as neurotransmitter receptor activity, which provided a scientific basis for its clinical application.

Occupational dust exposure-related chronic obstructive pulmonary disease: a bibliometric and visual analysis / 中国职业医学

OBJECTIVE: To analyze the current status and research hotspots of occupational dust exposure-related chronic obstructive pulmonary diseases(COPD). METHODS: Publications were searched and collected from the CNKI, SinoMed, PubMed and EMBASE. The high frequency key words were visually analyzed using NoteExpress V3.0 and VOSviewer 1.6.10, and content analysis was used to analyze research hotspots. RESULTS: A total of 3 095 COPD publications related to occupational dust exposure were retrieved. The first paper on COPD was published in 1973 in Chinese literature, and the number of publications had been on the rise since 2006. A total of 410 journals and 980 research institutions had published relevant articles. The first paper on COPD was published in 1950 in English literature, with a peak in publication after 2014. A total of 523 journals and 109 countries or regions had published relevant articles. The results of keyword co-occurrence analysis showed that COPD studies related to dust exposure mainly focused on epidemiology, risk factors and clinical characteristics. CONCLUSION: The number of research papers on occupational dust exposure-related COPD has been on the rise. The research papers mainly focus on epidemiology, risk factors and clinical characteristics of COPD.