Ligustilide delays senescence of auditory cortex in mice by inhibiting ferritinophagy / 中国药理学通报

Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

Advances on pentraxin 3 in osteoporosis and fracture healing / 中国骨伤

Pentaxin 3 (PTX3), as a multifunctional glycoprotein, plays an important role in regulating inflammatory response, promoting tissue repair, inducing ectopic calcification and maintaining bone homeostasis. The effect of PTX3 on bone mineral density (BMD) may be affected by many factors. In PTX3 knockout mice and osteoporosis (OP) patients, the deletion of PTX3 will lead to decrease of BMD. In Korean community "Dong-gu study", it was found that plasma PTX3 was negatively correlated with BMD of femoral neck in male elderly patients. In terms of bone related cells, PTX3 plays an important role in maintaining the phenotype and function of osteoblasts (OB) in OP state;for osteoclast (OC), PTX3 in inflammatory state could stimulate nuclear factor κ receptor activator of nuclear factor-κB ligand (RANKL) production and its combination with TNF-stimulated gene 6(TSG-6) could improve activity of osteoclasts and promote bone resorption;for mesenchymal stem cells (MSCs), PTX3 could promote osteogenic differentiation of MSCs through PI3K/Akt signaling pathway. In recent years, the role of PTX3 as a new bone metabolism regulator in OP and fracture healing has been gradually concerned by scholars. In OP patients, PTX3 regulates bone mass mainly by promoting bone regeneration. In the process of fracture healing, PTX3 promotes fracture healing by coordinating bone regeneration and bone resorption to maintain bone homeostasis. In view of the above biological characteristics, PTX3 is expected to become a new target for the diagnosis and treatment of OP and other age-related bone diseases and fracture healing.

Effects of traditional korean medicine Lurong Dabu Decoction on TLR4/WNT-5A signaling pathway in guinea pigs with cough variant asthma / 中国药理学通报

Aim To discuss the mechanism of Lurong Dabu Decoction on cough variant asthma. Methods Guinea pigs were divided into normal group(CON), model group(OVA), Lurong Dabu Decoction high-dose group(HIGH),low-dose group(LOW), and dexamethasone group(DEX)at random. The CVA model was established by smoking plus injection of OVA, aluminum hydroxide solution and nebulized inhalation to stimulate cough. Gguinea pigs were dissected 24 hours after the last challenge to obtain alveolar lavage fluid(BALF)and lung tissues. Immunoadsorption(ELISA)method was applied to detect the types of inflammatory cells and the content of inflammatory cytokines in BALF; HE and Masson staining of the middle lobe of the left lung were used to observe the pathological changes in lung tissues; immunohistochemical staining was used to observe TLR4 and WNT-5A protein expression and distribution of lung tissues; the protein extracted from the upper lobe of the left lung was used to measure the level of TLR4 and WNT-5A protein in lung tissues by Western blot; immunofluorescence was employed to measure the fluorescence intensity of TLR4 and WNT-5A in lung tissues; flow cytometry was used to detect IL-4 and IFN-γ in guinea pig lung tissues. Results Lurong Dabu Decoction could improve guinea pig airway inflammation, inhibit collagen fiber deposition, reduce the content of IL-4, IL-5, and IL-13 in BALF, and inhibit the protein expression of TLR4 and WNT-5A in lung tissues and increase IFN-γ levels in lung tissues while decreasing IL-4 levels. Conclusion Lurong Dabu Decoction may inhibit the occurrence of CVA through TLR4/WNT-5A signaling pathway.

Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study / 中华血液学杂志

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification / 医学前沿

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.

The abnormalities of free uroflow curve in female patients with detrusor underactivity and their clinical significance / 中华泌尿外科杂志

Objective:To explore the features of free uroflow(FF) curve patterns in female patients with detrusor underactivity(DU) and their clinical significance.Methods:Data of 275 adult female patients with lower urinary tract symptoms(LUTS) underwent urodynamic studies(UDS) at urology center of our hospital from June 2014 to June 2016 were analyzed retrospectively. The uroflow curve patterns of patients with DU were classified and analyzed in the context of parameters of FF, cystometry (CM), and pressure-flow study(PFS). The prevalence of each abnormal uroflow curve pattern in DU patients were calculated and compared with those in non-DU patients.Results:No bell-shaped curve was found in 141 patients with DU. The abnormal curve patterns can be divided into 5 types: Type Ⅰ (bell-shaped curve with saw tooth) in 20 cases (14.2%), Type Ⅱ (box-like curve) in 34 cases (24.1%), Type Ⅲ (triangle curve with decreasing slop) in 62 cases(43.9%), Type Ⅳ (triangle curve with increasing slop) in 4 cases (4.3%), Type Ⅴ (tide-wave curve)in 19 cases (13.5%). Maximum flow rate of free uroflow(Q max.FF) of type Ⅰ [(28.4±9.7) ml/s] was significantly greater than that of type Ⅱ, Ⅲ and Ⅴ[(17.0±4.1), (15.8±5.4) and (12.9±6.4) ml/s, P<0.05]. Flow time of free uroflow(FT.FF) of type Ⅲ and Ⅴ [(43.7±17.2) and (50.1±28.9)s] were significantly longer than that of type Ⅰ and Ⅱ [(18.5±7.3)s and (27.2±9.7)s, P<0.05]. Post voided residual > 50ml was noted in 19 cases (30.6%) of type Ⅲ, 7 cases (36.8%) of type Ⅴ, 1 case (2.9%) of type Ⅱ and no one in type Ⅰ and Ⅳ. Abnormal manifestations in cystometry mainly included bladder hypersensitivity, detrusor overactivity, and stress urinary incontinence. Detrusor pressure at Q max (Pdet.Q max) of type Ⅴ [(7.4±5.0) cmH 2O] was significantly lower than that of type Ⅰ, Ⅱ, Ⅲ [(11.8±6.7), (12.0±5.3), (12.1±5.0) cmH 2O, P<0.05]. Among 134 cases of non-DU, there were type Ⅰ curves in 88 cases (65.7%), type Ⅱ curves in 4 cases (2.9%), type Ⅲ curves in 15 cases (11.2%), type Ⅳ curves in 1 cases (0.7%), type Ⅴ curves in 7 cases (5.2%). And normal bell-shaped curves in 19 cases(14.2%). The prevalence of type Ⅱ, Ⅲ and Ⅴ in DU patients was significantly higher than that in the non DU patients ( P<0.05). Conclusions:This study reveals that the characteristics of reduced detrusor contractility and duration, prolonged bladder emptying or incomplete emptying can be reflected in the patterns of free uroflow curve in female patients with DU. The abnormalities of these free uroflow curve patterns, especially type Ⅱ, Ⅲ and Ⅴ will be helpful in preliminarily screening DU in females.

Calycosin inhibits proliferation and migration of human triple-negative breast cancer cells through intervening Hippo pathway / 中国药理学通报

Aim To study the effects of calycosin on proliferation and migration of human triple-negative breast cancer MDA-MB-231 cells and the underlying mechanisms. Methods MDA-MB-231 cells were intervened by calycosin,and the proliferation ability was detected by CCK-8 method. The apoptosis and cycle of MDA-MB-231 cells were detected by flow cytometry. The effect of calycosin on the migration of MDA-MB-231 cells was observed using cell scratch. The mRNA expression of EMT related genes was detected by RT-PCR. The effects of calycosin on the expression of key proteins of Hippo pathway and EMT related proteins were detected by Western blot. Results Calycosin could significantly inhibit the proliferation,migration and apoptosis of MDA-MB-231 cells,and markedly inhibit the expression of Hippo signaling pathway and EMT related protein. Conclusion Calycosin may induce MDA-MB-231 cell apoptosis,block cell cycle and inhibit cell migration by inhibiting Hippo signaling pathway and EMT pathway.

Experimental Research Progress of Replenishing Qi and Activating Blood Circulation Traditional Chinese Medicine on Mitochondrial Quality Control in Treatment of Chronic Heart Failure / 中国实验方剂学杂志

Heart failure is a complex clinical syndrome，which is the final result of compensatory failure of heart injury caused by various reasons. Long-term persistent cardiac stress leads to mitochondrial dysfunction，which in turn further damages cardiomyocytes and leads to disease progression. Timely removal of damaged mitochondria in cardiomyocytes and maintaining a good living environment of viable mitochondria is not only an effective means to protect cardiomyocytes，but also a new way to prevent and treat heart failure and ventricular remodeling. Mitochondrial quality control is a series of cellular activities for mitochondria to maintain their structural and functional stability，including oxidative stress response，regulation of mitochondrial dynamics，mitochondrial autophagy，intracellular calcium regulation and so on. Traditional Chinese medicine（TCM） mostly uses drugs of replenishing Qi and activating blood circulation in the treatment of chronic heart failure，and Qi and mitochondria are similar in function. According to TCM，the performance of the body as "static，descending and inhibitory" in the case of Qi deficiency can also be compared with the energy defect of mitochondria. The classical method of tonifying qi and activating blood circulation in TCM can be applied here. In recent years，TCM takes mitochondria as the target and carries out many related experimental studies from the point of view of myocardial energy supply. It is found that Chinese herbs for replenishing Qi and activating blood circulation can participate in regulating the quality control mechanism of intracellular mitochondria with multiple targets and links. It is proved by experiments that Chinese herbs for replenishing Qi and activating blood circulation can exert myocardial protective effect through this mechanism.

Research of Influence on Inflammation of Xieheyin on PCOS-IR Mice Based on Intestinal Mucosal Barrier and TLR4/NF-κB/NLRP3 Pathway / 中国实验方剂学杂志

Objective:To investigate the possible mechanism of Xieheyin in alleviating obese polycystic ovary syndrome with insulin resistance（PCOS-IR）and reducing inflammatory response. Method:Ten of sixty SPF femlae C57BL/6J mice were randomly selected as the normal group，and the rest mice were given letrozole 0.002 g·kg^-1 combined with fecal suspension 2 g·kg^-1 for 28 consecutive days to establish model of PCOS-IR.The mice that were successfully modeled were randomized into the model group，metformin group（0.25 g·kg^-1），and low（10 g·kg^-1），medium（20 g·kg^-1），and high-dose（40 g·kg^-1）Xieheyin groups，and administered with the corresponding drugs by gavage，once a day，for four consecutive weeks. Except the normal control group， the mice in the other groups were continuously given fecal suspension combined with letrozole solution to maintain the model during the treatment. The mice were weighed once a week.Levels of fasting blood glucose （FBG） were detected by blood glucose test strips.And enzyme-linked immunosorbent assay （ELISA） method was used to detect serum testosterone（T），follicle stimulating hormone（FSH），luteinizing hormone（LH），fasting insulin（FINS）level，and LH/FSH and Homeostasis model assesment of insulin resistance （HOMA-IR） were calculated．The uterus and ovaries were weighed and fixed.Hematoxylin-eosin（HE）staining was used to observe ovarian tissue pathology morphology. Western blot was used to detect the expression levels of tight junction key molecular zonula occludens 1（ZO-1），occludin in colon tissues，and the expression levels of Toll-like receptor 4/nuclear factor kappa B/Nod-like receptor protein 3（TLR4/NF-<italic>κ</italic>B/NLRP3）signaling pathway and inflammation associated proteins cysteinyl aspartate specific proteinase-1（Caspase-1） and interleukin-1<italic>β</italic>（IL-1<italic>β</italic>） in colon tissues. Result:Compared with normal control group，the body weight of mice in the model control group increased significantly（<italic>P</italic><0.01）. Serum FINS，FBG，HOMA-IR，T，LH/FSH were significantly increased（<italic>P</italic><0.05，<italic>P</italic><0.01）. The uterine organ ratio were decreased significantly（<italic>P</italic><0.01），while the ovarian organ ratio were significantly increased（<italic>P</italic><0.01）. The number of atresia follicles and cystic dilatation follicles increased significantly，and the number of corpus luteum significantly decreased，the thickness of follicular granulosa cells also decreased，while the white membrane thickness of the ovary increased. Tight junction related ZO-1，occludin proteins in colon tissues were all decreased（<italic>P</italic><0.01）.The relative expression levels of inflammation-related protein IL-1<italic>β</italic>，Caspase-1 and TLR4/NF-<italic>κ</italic>B/NLRP3 target protein signaling pathway were significantly increased（<italic>P</italic><0.05）.Compared with model control group， the body weight of mice in the low，middle and high dose Xieheyin group decreased significantly（<italic>P</italic><0.01）. The serum T，LH/FSH，FINS，FBG，HOMA-IR were significantly decreased（<italic>P</italic><0.05，<italic>P</italic><0.01）. The uterine organ ratio were increased（<italic>P</italic><0.05），while the ovarian organ ratio were decreased（<italic>P</italic><0.05）. The number of cystic follicles decreased and corpus luteum increased，the thickness of follicular granulosa cells increased and be arranged normally，while the white membrane thickness of the ovary increased slightly. The expressions of ZO-1，occludin proteins were increased（<italic>P</italic><0.01）. The expression levels of IL-1<italic>β</italic>，Caspase-1 and TLR4/NF-<italic>κ</italic>B/NLRP3 target protein in the high dose group were significantly decreased（<italic>P</italic><0.01）. Conclusion:Xieheyin could activate intestinal TLR4/NF-<italic>κ</italic>B/NLRP3 signaling pathway，inhibit pro-inflammatory factor secretion，improve obesity and IR，which was correlated with rebuilding intestinal mucosal barrier and inhibiting intestinal inflammation．

Effect of Elian Granule on Autophagy and PI3K/Akt/mTOR Signaling Pathway in Gastric Tissue of Rats with Gastric Cancer / 中国实验方剂学杂志

Objective:To investigate the effect of Elian granule on autophagy and the phosphatidylinositol -3 kinase （PI3K）/protein kinase B （PKB/Akt）/mammalian target of rapamycin （mTOR） signaling pathway in gastric tissue of rats with gastric cancer. Method:SPF SD rats were randomly divided into the normal， model， Elian granule， and Weifuchun groups. In addition to the routine feeding in the normal group， the model， Elian granule， and Weifuchun groups received <italic>N</italic>-methyl-<italic>N</italic>'-nitro-<italic>N</italic>-nitrosoguanidine （MNNG） to induce gastric cancer in rats， and they were respectively given normal saline， Elian granule aqueous solution （3.240 g·kg^-1） and Weifuchun aqueous solution （0.390 g·kg^-1） by gavage （<italic>ig</italic>） for 48 weeks. The gross changes of the stomach taken by laparotomy were observed by naked eyes. Hematoxylin-eosin （HE） staining was performed to observe the histopathological changes of the gastric tissue in rats. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot （WB） were used to detect the mRNA and protein expression of microtubule-associated protein 1 light chain 3 beta （LC3B）， Beclin1， p62， PI3K， Akt， mTOR in rat gastric tissue. Result:Compared with the normal group， the model group showed gastric distension， thinner gastric wall， pale gastric mucosa， atrophied and flat folds， disordered course， and visible nodules and vegetations. Compared with the model group， the Elian granule group demonstrated alleviated gastric distension， dark gastric mucosa， reduced folds， and regular course， with the thinned gastric wall improved and granular nodules observed occasionally. According to HE staining， compared with the normal group， the model group showed crowded and disordered rat gastric glands， diverse in shape， varied cell morphology， basophilic cytoplasm， large irregular hyperchromatic nuclei， visible mitosis， and infiltrated and destroyed muscularis mucosae. While compared with the model group， the arrangement of gastric glands was regular， and a few mildly atypical cells could be observed in rats of the Elian granule group. Compared with the normal group， the model group exhibited decreased expression of LC3B and Beclin1 mRNA and protein in gastric tissue （<italic>P</italic><0.05）， and increased expression of PI3K， p62， Akt， and mTOR mRNA and protein （<italic>P</italic><0.05）. Compared with the model group， the Elian granule group showed increased expression of LC3B and Beclin1 mRNA and protein in gastric tissue （<italic>P<</italic>0.05）， and decreased expression of PI3K mRNA and p62， Akt， and mTOR mRNA and protein （<italic>P</italic><0.05）. Conclusion:Elian granule can improve the cell atypia of gastric tissue in rats with gastric cancer， and the mechanism may be related to the inhibition of the PI3K/Akt/mTOR signaling pathway to promote autophagy.

Effect of Chaihu Shugansan on Mitochondrial Function and Mitophagy in Gastric Tissue of Rats with Functional Dyspepsia / 中国实验方剂学杂志

Objective:To observe the effects of Chaihu Shugansan on gastric motility and mitochondrial function and mitophagy in rats with functional dyspepsia （FD） and to preliminarily reveal its mechanism in preventing and treating FD. Method:Thirty-two SD rats of SPF grade were randomly divided into the normal group， model group， Chaihu Shugansan （4.8 g·kg^-1） group， and domperidone group （4.5 mg·kg^-1） after one week of adaptive feeding， with eight rats in each group. Rats in all groups except for the normal group were exposed to modified tail-clamping stimulation for inducing FD. Four weeks later， the semi-solid nutritive medium was used to observe the gastric emptying rate of FD rats， and the serum citrate synthase （CS）， motilin （MTL）， and gastrin （GAS） were detected by enzyme-linked immunosorbent assay （ELISA）. The pathological changes in gastric tissue were observed by hematoxylin-eosin （HE） staining， the mitochondrial characteristics by transmission electron microscopy， and the expression of microtubule-associated protein light chain 3 （LC3） and voltage-dependent anion-selective channel 1 （VDAC1） by immunofluorescence co-localization. The mitochondria were extracted from fresh gastric tissue for measuring the reactive oxygen species （ROS）， malondialdehyde （MDA）， and superoxide dismutase （SOD） levels using the biochemical kits. The mitochondrial LC3， yeast Atg6 homologous（Beclin1）， and p62 protein expression was assayed by Western blot. Result:Compared with the normal group， the model group exhibited significantly reduced gastric emptying rate （<italic>P</italic><0.01） and serum CS， MTL， and GAS levels （<italic>P</italic><0.01）. HE staining showed no pathological changes like erosion or ulcer in the gastric tissue of rats in each group. However， the mitochondria in the gastric tissue were observed swollen and dilated under the transmission electron microscope， and vacuolar lesions appeared. The co-expression of LC3 with VDAC1 increased significantly （<italic>P</italic><0.01）. The mitochondrial ROS and MDA levels were elevated significantly （<italic>P</italic><0.01）， while SOD content was significantly reduced （<italic>P</italic><0.01）. The protein expression levels of LC3 and Beclin1 were significantly up-regulated （<italic>P</italic><0.05， <italic>P</italic><0.01）， whereas p62 protein expression was down-regulated significantly （<italic>P</italic><0.01）. Compared with the model group， Chaihu Shugansan and domperidone elevated the gastric emptying rate （<italic>P</italic><0.05） and serum CS， MTL， and GAS levels （<italic>P</italic><0.05， <italic>P</italic><0.01）. It was observed under the transmission electron microscope that the mitochondrial nuclear membrane of the gastric tissue was intact， with clear structure and high density of mitochondrial cristae， and mitochondrial fission and fusion were observed in some parts. The co-localization area of LC3 and VDAC1 was significantly reduced （<italic>P</italic><0.01）. The mitochondrial ROS and MDA levels declined significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）， whereas SOD level rose （<italic>P</italic><0.05）. The protein expression levels of LC3 and Beclin1 were significantly down-regulated （<italic>P</italic><0.05， <italic>P</italic><0.01）， while that of p62 was obviously up-regulated （<italic>P</italic><0.01）. Conclusion:The mechanism of Chaihu Shugansan in preventing and treating FD may be related to the improvement of mitochondrial function and the inhibition of mitophagy in gastric tissue.

Effects of Mirror Therapy on Upper Limb Motor Function and Corticospinal Tract Remodeling after Stroke: A Diffusion Tensor Imaging Study / 中国康复理论与实践

Objective:To explore the effects of mirror therapy on upper limb motor function recovery and corticospinal tract remodeling after stroke. Methods:From March, 2017 to March, 2019, 42 subcortical stroke patients with upper limb dysfunction from Shanghai Fifth People's Hospital were randomly divided into control group (n = 21) and observation group (n = 21). Both groups received routine rehabiliation, while the observation group received mirror therapy additionally, for twelve weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), and scanned with diffusion tensor imaging (DTI) before and after treatment. The fractional anisotropy (FA) in posterior limb of internal capsule (PLIC) was obtained. Results:The scores of FMA-UE improved in both groups after treatment (t > 9.560, P < 0.001), and improved more in the observation group than in the control group (t > 2.634, P < 0.05). FA decreased significantly in the affected-lateral PLIC compared with that in the unaffected-lateral PLIC in both groups (t > 11.368, P < 0.001). FA in the affected side increased significantly after treatment in the observation group (t = 2.385, P < 0.05), while there was no significant difference in the control group (t = -0.596, P > 0.05). FA increased more significantly in the observation group than in the control group (t = 2.306, P < 0.05). Conclusion:Mirror therapy can promote the recovery of motor function of upper limb and the corticospinal tract remodeling in stroke patients.

Effects of intervention of hot spring bathing on antioxidation functions in population / 上海预防医学

Objective To understand the influence of hot spring bathing intervention on population's antioxidation functions. Methods Three typical types of hot spring(metasilicic acid type, warm mineral type and temperature type)in Guizhou Province were selected for investigation. According to the inclusion-exclusion criteria, questionnaires and physical examinations results, 421 individuals were selected as observation subjects for hot spring bathing intervention, of which 311 subjects completed 40 to 50 minutes of intervention once a day, 5 days a week, and for 4 weeks. Two physical examinations before and after the intervention were conducted for the 311 subjects. The fasting venous blood samples on the mornings of two physical examinations were collected and the serum was separated. Levels of serum oxidative stress-related parameters including total superoxide dismutase(T-SOD), copper zinc superoxide dismutase(Cu-Zn SOD), glutathione sulfur transferases(GSTs)glutathione peroxidase(GSH-px), sulfhydryl(-SH)and malondialdehyde(MDA)were measured by enzymatical methods. Results The overall comparison showed that compared with before the bathing intervention, the levels of antioxidant enzymes including T-SOD, Cu-Zn SOD, GSTs and GSH-px significantly increased in serum after the intervention(all P < 0.05). There was an increasing trend of serum -SH level after the intervention, but with no statistical differences were seen(P > 0.05). MDA, a product of lipid peroxidation, significantly decreased in serum after the intervention(P < 0.05). The results of classified comparison showed that the effects of different hot spring types on antioxidant enzymes were different. Metasilicic acid type significantly increased the activities of GSTs and GSH-px in serum(all P < 0.05), warm mineral type significantly increased the activities of T-SOD and Cu-Zn SOD in serum(all P < 0.05), and temperature type significantly increased the activities of T-SOD, Cu-Zn SOD and GSTs in serum(all P < 0.05). There were increasing trends of serum -SH levels after bathing intervention of all three hot spring types, but no statistical differences were seen(all P > 0.05). The serum MDA levels decreased significantly after bathing intervention of all three types of hot springs(all P < 0.05). Conclusion Overall, bathing intervention of hot springs can improve the activities of antioxidant enzymes and reduce lipid peroxidation products in population. The results of oxidative stress parameters are slightly different in different types of hot springs. The subjects mainly show the elevation of glutathione related enzyme(GSTs and GSH-px)activities after intervention of metasilicic acid type, the elevation of superoxide dismutase(SOD)activities after intervention of warm mineral type and temperature type, and the decline of lipid peroxidation levels after intervention of all three types. It suggests that hot spring bathing may have certain effects on improving the body's antioxidation functions.

Study on the effect of hot spring bath therapy on sleep quality based on health bracelets / 上海预防医学

Objective To study the relieving effects of hot spring bath therapy on sleep quality for people with sleep disorders based on data from health bracelets. Methods After health examinations, 311 people with sleep disorders who participated in the bath therapy in five typical hot spring areas in Guizhou Province were selected as the subjects. A four-week hot spring bath therapy was implemented, and the bathing method and the classification of hot springs were the same as the"Overview of study of the physiotherapy efficacy of typical hot springs in Guizhou Province". The daily sleep time at night(minutes), deep sleep ratio(%), light sleep ratio(%)and rapid eye movement ratio(%)for all subjects were collected using the Huawei Honor Band 3 health bracelets. Repeated measures analysis of variance was used to compare the differences in sleep quality indicators of each group at night each week. The effect of three different hot spring bath therapies on the improvement of night sleep quality was evaluated by factor analysis. Results Hot spring bath therapy can increase night sleep time and deep sleep ratio, while reducing light sleep ratio. Compared with the first week, the night sleep time in the following three weeks significantly increased(P < 0.05), especially in the fourth week; the deep sleep ratio during the third and fourth weeks was significantly higher than during the first and second weeks(P < 0.05), but the light sleep ratio was lower than during the first and second weeks(P < 0.05). The rapid eye movement ratio did not change significantly throughout the 4 weeks(P > 0.05). Further classified according to the physiotherapy components of geological hot springs, the results showed that the water temperature type of hot springs can increase night sleep time and reduce light sleep ratio; the warm mineral type of hot springs has a certain regulatory effect on increasing night sleep time, deep sleep ratio and reducing light sleep ratio; the metasilicic acid type of hot springs can improve night sleep quality by increasing night sleep time and deep sleep ratio, while reducing light sleep ratio and rapid eye movement ratio. The factor analysis results suggest that the metasilicic acid type of hot springs is better than the water temperature type and warm mineral type of hot springs in improving night sleep quality. Conclusion Hot spring bath therapy can improve the night sleep quality for people with sleep disorders to varying degrees, and the metasilicic acid type of hot springs is relatively better than other types.

Intervention effects of hot spring bathing on blood pressure, resting heart rate, cardiovascular function indicators and physical signs in population with high-normal blood pressure / 上海预防医学

Objective To investigate the effects of hot spring baths on blood pressure, resting heart rate, cardiovascular function related indicators and physical signs in population with high-normal blood pressure. Methods Residents of typical hot spring areas in Guizhou Province were included as the subjects. According to the epidemiological survey of the research group and the physical examination results before the intervention, combined with the inclusion and exclusion criteria, a total of 217 people with high normal blood pressure were selected as the observation subjects. The intervention of hot spring baths was carried out for four weeks, once time per day, 5 times per week, for 40-50 minutes each time. After the intervention, the blood pressure, resting heart rate and serum levels of creatine kinase(CK), lactate dehydrogenase(LDH), and α-hydroxybutyrate dehydrogenase(α-HBDH)were detected, and the improvement of cardiovascular related signs(palpitation, dizziness/headache, cough/sputum and night sweats)were clinically examined. SPSS 23.0 software was used for statistical analysis. Results Paired t-test results showed that the systolic blood pressure, diastolic blood pressure and resting heart rate of 217 high normal blood pressure subjects were significantly lower after hot spring baths(P < 0.01). Further analysis revealed that the number of people with high normal blood pressure dropped from 217 to 128 after the hot spring baths. Before the intervention, 95 of the 217 people with high-normal blood pressure had resting heart rates between 80 and 90 beats/min, and 35 of them above 90 beats/min. After the intervention, the resting heart rates of those above people decreased to 68 and 14, respectively. Serum levels of cardiovascular related indicators showed that CK, LDH, and α-HBDH levels in people with high-normal blood pressure decreased to some extent after the intervention, and CK level was significantly lower than that before the intervention(P < 0.05). The results of clinical examination showed that hot spring baths had a significant improvement effect on palpitation, dizziness/headache, cough/expectoration, and night sweats in people with high-normal blood pressure. Conclusion The typical hot spring baths in Guizhou Province can reduce the blood pressure and resting heart rate in population with high-normal blood pressure, and improve the cardiovascular function related indicators and physical signs to a certain extent.

Effect of moxibustion on cardiac function and expression of autophagy-related proteins of cardiomyocytes in chronic heart failure rats / 针刺研究

OBJECTIVE: To observe the effect of moxibustion on cardiac function and expression of myocardial tumor suppressor protein p53, mammalian target of rapamycin (mTOR) and phosphorylated(p)-mTOR (excessive autophagy-associated proteins of cardiomyocytes) in rats with chronic heart failure (CHF), so as to explore its mechanisms underlying improvement of CHF. METHODS: SD rats were divided into blank control (n＝11), model(n＝8), autophagy activator (n＝8), autophagy inhibitor (n＝9) and moxibustion(n＝9) groups. The CHF model was established by i．p. injection of Doxorubicin Hydrochloride (DOX, 1 mg/mL, 1-4 mg/kg) every other day. Moxibustion was applied to bilateral "Feishu" (BL13) and "Xinshu" (BL15) for 20 min, 5 times a week for 3 weeks. Rats of the autophagy activator group received gavage of Rapamycin (RAPA, 2 mg/kg) and those of the autophagy inhibitor group received i．p. injection of Methyladenine (3-MA, 15 mg/kg) 5 times a week for 3 weeks after successful modeling. The heart weight and body weight were measured to calculate heart mass index (HW/BW＝heart weight ÷ body weight). Cardiac output (CO) and heart rate (HR) were measured by using a cardiac function meter. Serum N-terminal pro-brain natriuretic peptide (NT-pro BNP) content was assayed by using ELISA, and the expression of myocardial p53, p-mTOR and mTOR proteins was examined by Western blot. RESULTS: (1) Compared with the blank control group, the HR, HW/BW, NT-pro BNP content and p53 expression levels were significantly increased (P<0.01), and the CO and ratio of p-mTOR/mTOR were significantly decreased in the model group (P<0.01). (2) Compared with the model group, the HR, HW/BW and NT-pro BNP content of the autophagy inhibitor and moxibustion groups were significantly decreased (P<0.01, P<0.05), and CO and p-mTOR/mTOR ratio were significantly increased in both autophagy inhibitor and moxibustion groups (P<0.01). (3) Compared with the autophagy activator group, the levels of HR, HW/BW, NT-pro BNP and p53 in the autophagy inhibitor and moxibustion groups were significantly lower (P<0.01), and those of CO and p-mTOR/mTOR levels were significantly higher (P<0.01). CONCLUSION: Moxibustion, similar to the autophagy inhibitor, has a protective action on myocardium in CHF rats, which is possible by preventing over expression of myocardial autophagy-associated proteins during CHF.

Transfection of microRNA-21 mediating the biological behavior and cellular radiosensitivity of esophageal squamous carcinoma cells / 解剖学报

Objective To study the biological properties of microRNA (miRNA) -21 expression in esophageal squamous cell carcinoma. Methods MiRNA-21 sense expression vector, miRNA-21 empty vector and miRNA-21 inhibitor were transfected and detected by fluorescence Real-time PCR. The normal cells of esophageal squamous cell carcinoma TE-1 were used as the control group, and the transfection result were detected. The cell proliferation activity was detected by cell counting kit-8(CCK-8), and the apoptosis ability was detected by flow cytometry. The invasion ability and migration ability of TE-1 cells were observed by Transwell chamber and scratch test. Changes in the sensitivity of TE-1 cells to radiotherapy were observed by colony formation experiments. The data were analyzed using SPSS 19. 0 software. Results The result of Real-time PCR showed that the expression level of miRNA-21 in TE-1 cells was significantly decreased after transfected with miRNA-21 inhibitor (P<0. 05). Compared with the normal cell growth group, positive control group and negative control group, the proliferation of TE-1 cells was reduced and apoptosis was accelerated after transfection with miRNA-21 inhibitor (P<0. 05). In addition, the ability of cell invasion and migration in the experimental inhibition group was decreased. Clone formation assays showed that inhibition of miRNA-21 expression significantly increased the sensitivity of TE-1 cells to radiation. Conclusion Down-regulation of miRNA-21 reduces the proliferation, invasion, migration and sensitivity of radiotherapy in esophageal squamous cell carcinoma TE-1 cells, and is a potential target for the future treatment of esophageal cancer.

Clinical analysis of 30 cases of Castleman disease with different types of thoracic involvement / 中华血液学杂志

Objective: To improve the clinical understanding of Castleman disease (CD) with different types of thoracic involvement, including their clinical features, radiological and pathological findings, diagnosis and current treatment strategies. Methods: Retrospective analysis of 30 patients diagnosed with CD with thoracic involvement and hospitalized between June 2009 and May 2019 in The First Affiliated Hospital of Guangzhou Medical University was performed. Patients were divided into three groups for subsequent analysis based on the clinical data: CD with bronchiolitis obliterans (BO) , unicentric Castleman disease (UCD) without BO, and multicentric Castleman disease (MCD) without BO. Results: Among the 30 patients, there were 5 (16.7%) patients diagnosed with BO, 18 (60.0%) patients had UCD without BO and 7 (23.3%) patients had MCD without BO. The average age of MCD without BO patients was significantly older than that of BO and UCD without BO patients[ (49.29±5.39) ys vs (27.20±3.76) ys and (37.17±2.87) ys; P=0.005 and 0.034, respectively) ]. Pulmonary symptoms were commonly seen in BO group (100%) and MCD without BO group (71.4%) . while no pulmonary symptoms were seen in UCD without BO group. Key abnormal laboratory findings were erythrocyte sedimentation rate (ESR) increase (40%in BO group and 57.1% in MCD without BO group) and hypoxia (60% in BO group and 28.6% in MCD without BO group) . Other abnormal laboratory findings seen in MCD without BO group included anemia and IgG increase (both 57.1%) . Notably, all patients in BO group had extremely severe mixed ventilation dysfunction in the lung function test. CT scan showed lung parenchyma involvement in BO group (100%) , in UCD without BO group (11.1%) featured by solitary pulmonary nodule and in MCD without BO group (57.1%) featured by diffuse lesions in bilateral lungs. The size of lymph nodes was significantly smaller in MCD without BO group comparing to that in BO group and UCD without BO group[short diameter (1.83±0.51) cm vs (4.73±1.63) cm and (3.62±0.26) cm; P=0.006 and 0.011, respectively]. All patients (100%) in the BO group had a pathological type of transparent vascular variant while the same pathological type accounts for 88.9% in UCD without BO patients. The predominantly pathological type (57.1%) was plasma cell variant in the MCD without BO group. Oral ulcers presented in all patients in BO group but were relieved after the mass resection and immunomodulatory therapy, but the pulmonary symptoms were still progressively aggravated. Thoracoscopic mass excision was the main treatment for UCD without BO patients while chemotherapy, immunomodulatory and targeted therapy were commonly used for MCD without BO treatment. Conclusion: The age, clinical symptom, laboratory finding, lung function, imaging manifestation, pathology, treatment and prognosis were different among the three groups. This classification could improve clinical understanding of the disease.

Safety and efficacy of sacral neuromodulation therapy for lower urinary tract dysfunction in elderly people: A multicenter study / 中华老年医学杂志

Objective:To investigate the safety and efficacy of sacral neuromodulation(SNM)therapy for the treatment of lower urinary tract dysfunction(LUTD)in elderly patients.Methods:Clinical data of 91 elderly patients with LUTD from multiple medical institutions who received SNM during the period from January 2012 to December 2016 were retrospectively analyzed.Patients were divided into four groups: the interstitial cystitis(IC)group(n=28), the neurogenic bladder(NB)group(n=36), the overactive bladder syndrome(OAB)group(n=13)and the idiopathic dysuria(ID)group(n=14). Different sets of evaluation parameters were used for different diseases.Patients’ baseline data and data in stage I(test phase)and stage Ⅱ(permanent SNM)were recorded, statistically analyzed and compared.Results:Ninety-one people underwent SNM treatment.Of them, 53 patients received permanent implants(stage Ⅱ), and the total conversion rate of stage I to stage Ⅱ was 58.2%(53/91). Patients receiving permanent implants(stage Ⅱ)had a preoperative period ranging from 3 months to 30 years, and were followed up for 2 to 58 months after treatment, with an average follow-up of 19.6 months.The improvement rates in stage I for urinary urgency, daily urination frequency, daily nocturnal urination frequency, maximum urine volume, daily average urine volume, daily urine leakage frequency, and quality of life score were 35.4%, 31.6%, 33.7%, 32.6%, 49.2%, 43.2% and 13.2%, respectively.The improvement rates in stage Ⅱ for urinary urgency, daily urination frequency, daily nocturnal urination frequency, maximum urine volume, daily average urine volume, daily urine leakage frequency, and quality of life score were 43.2%, 40.0%, 37.8%, 50.5%, 70.5%, 70.4% and 43.2%, respectively.Three adverse events occurred, including 1 case of recurrent symptoms, 1 case of moderate infection, and 1 case of electrical lead dislocation.Conclusions:Sacral nerve stimulation has definitive and consistent curative effects on LUTD in elderly people.The follow-up time should be extended to further study the safety of sacral nerve stimulation.

DevelopmentofGroup 2InnateLymphoidCell-dominantAllergicAirway InflammationinMice / 中山大学学报(医学科学版)

@#【Objectives】Todevelopagroup2innatelymphoidcell（ILC2）-dominantallergicairwayinflammation modelinwildtypeC57BL/6andT/Bcell-deficientRag1-/- mice.【Methods】FemaleC57BL/6andRag1-/- micewere randomlydividedintocontrolandmodelgroups.Themiceinmodelgroupswereadministeredintratracheallywith1μg IL-33in20μLH2Oondays1，3and5，andthecontrolmicewereadministeredaccordinglywith20μLH2O.Onday6， themiceweresacrificedforcollectionofbronchoalveolarlavagefluid（BALF）andthelungs.Thepulmonaryinflammation inmicewasevaluatedbypathologicalstainingforlungtissues，ELISAforlevelsofcytokinesinBALF，andflowcytometry analyses of ILC2 and inflammatory cells.【Results】Both the C57BL/6 and Rag1-/- mice with the treatment of IL-33 exhibitedobviouseosinophilicairwayinflammationinperi-trachealarea（P<0.05）andgobletcellhyperplasiainairway epithelium（P<0.05）.Comparedwiththecontrolmice，numbersofeosinophils（P<0.05）andneutrophils（P<0.05） aswellaslevelsofIL-5（P <0.05）andIL-13（P <0.05）inBALFwereincreasedinthemodelgroup.Inaddition， significantlyhigher levels of ILC2 were found in lung tissues of the model mice.【Conclusion】The ILC2-dominant allergicairwayinflammationwassuccessfullydevelopedinbothC57BL/6andRag1-/-mice，whichprovidedtheapproach toinvestigatetheroleofILC2inasthmaandallergicrhinitis.