Clinical efficacy of da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis / 中华消化外科杂志

Objective:To investigate the clinical efficacy of da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 7 patients who underwent da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis in Xinjiang Uiger Municipal People′s Hospital from October 2019 to July 2021 were collected. There were 3 males and 4 females, aged (43±12)years. Observation indicators: (1) surgical situations; (2) complications; (3) follow-up. Mea-surement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All 7 patients underwent da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis successfully, without conversion to laparotomy and laparoscopic surgery. None of the 7 patients underwent intraoperative blood transfusion and the operation time, volume of intraoperative blood loss, time to postoperative first and flatus, time to postoperative initial liquid food intake, time to postoperative abdominal drainage tube removal, time to postoperative urethral catheter removal, duration of postoperative hospital stay of 7 patients was (225±45)minutes, 100(range, 50-200)mL, (1.9±0.7)days, (4.2±1.2)days, (7±4)days, (2.9±0.8)days, (7±4)days, respectively. (2) Complications. None of the 7 patients had postoperative complications such as bile leakage, abdominal hemorrhage, incision infection, hydatid cavity infection, secondary operation, intestinal obstruction, pulmonary infection and deep venous thrombosis of lower limbs. (3) Follow-up. All 7 patients were followed up for 7 (range, 3-12) months. None of the 7 patients had recurrence of hepatic echinococcosis or peritoneal implantation and incision implantation, and all patients survived during follow-up.Conclusion:da Vinci Xi surgical system assisted laparoscopic exocytosis for hepatic echinococcosis is safe and feasible.

Y-box-binding protein 1 mediates sorafenib resistance via the extracellular signal regulated-protein kinase pathway in hepatoma cells / 中华肝脏病杂志

Objective: To investigate the effect and possible mechanism of Y-box-binding protein 1 (YB-1) on sorafenib resistance in hepatoma cells. Methods: Lentiviral vectors with YB-1 overexpression and knockdown were constructed, respectively, to stimulate human hepatoma cell lines (HepG2 and Huh7) alone or in combination with sorafenib.The overexpression part of the experiment was divided into four groups: overexpression control group (Lv-NC), YB-1 overexpression group (Lv-YB-1), overexpression control combined with sorafenib resistance group (Lv-NC+sorafenib), YB-1 overexpression combined with sorafenib resistance group (Lv-YB-1 + sorafenib). The knockdown part of the experiment was also divided into four groups: knockdown control group (Lv-shNC), YB-1 knockdown group (Lv-shYB-1), knockdown control combined with sorafenib resistance group (Lv-shNC + sorafenib), YB-1 knockdown combined with sorafenib resistance group (Lv-shYB-1 + sorafenib). The occurrence of cell apoptosis was detected by TUNEL. The protein expression levels of phosphorylated (p)-ERK and ERK, key proteins in the extracellular regulatory protein kinase (ERK) signaling pathway, were detected by Western blot and quantified by ImageJ software. Subcutaneous tumorigenesis experiments were performed in nude mice. The effect of YB-1 on the efficacy of sorafenib was verified in vivo. The comparison between the two sets of data was carried out by an independent sample t-test. One-way ANOVA was used for comparisons between the three groups of data above. Results: Sorafenib had accelerated the occurrence of apoptosis in hepatoma cells, while YB-1 overexpression had inhibited cell apoptosis, and at the same time also inhibited the apoptosis-accelerating impact of sorafenib. On the contrary, YB-1 knockdown accelerated cell apoptosis and amplified the induction effect of sorafenib on apoptosis. Furthermore, sorafenib resistance had down-regulated p-ERK levels (HepG2: Lv-NC 0.685 ± 0.143, Lv-NC + sorafenib 0.315 ± 0.168, P < 0.05; Huh7: Lv-NC 0.576 ± 0.078, Lv-NC + sorafenib 0.150 ± 0.131, P < 0.01), whereas YB-1 overexpression had inhibited sorafenib resistance p-ERK reduction (HepG2: Lv-NC + sorafenib 0.315 ± 0.168, Lv-YB-1 + sorafenib 0.688 ± 0.042, P < 0.05; Huh7: Lv-NC + sorafenib 0.150 ± 0.131, Lv-YB-1 + sorafenib 0.553 ± 0.041, P < 0.05). YB-1 knockdown further increased sorafenib-induced p-ERK downregulation (HepG2: Lv-shNC + sorafenib 0.911 ± 0.252, Lv-shYB-1 + sorafenib 0.500 ± 0.201, P < 0.05; Huh7: Lv-shNC + sorafenib 0.577 ± 0.082, Lv-shYB-1 + sorafenib 0.350 ± 0.143, P < 0.05), which was further verified in naked mice (Lv-shNC + sorafenib 0.812 ± 0.279, Lv-shYB-1 + sorafenib 0.352 ± 0.109, P < 0.05). Conclusion: YB-1 mediates the occurrence of sorafenib resistance via the ERK signaling pathway in hepatoma cells.

LncRNA SBF2-AS1 Regulates Invasion and Proliferation of Hepatocellular Carcinoma Cells Through miR-372-3p/CDK6 Axis / 肿瘤防治研究

Objective To investigate the effects of lncRNA SBF2-AS1 on the proliferation and invasion of hepatoma cells by regulating the miR-372-3p/CDK6 pathway. Methods Bel7402 and SK-hep1 cells were selected as research objects. The expression levels of SBF2-AS1, miR-372-3p, and CDK6 were up- or down-regulated according to different experimental stages, while the expression levels of miR-372-3p and CDK6 in cells were detected by real-time fluorescence quantitative PCR and Western blot. Dual luciferase reporter assay verified the targeting relationships between SBF2-AS1 and miR-372-3p as well as miR-372-3p and CDK6, respectively. CCK-8, colony formation assay, Transwell, cell cycle assay, and flow cytometry were used to analyze cell proliferation, colony formation, migration/invasion ability, cell cycle activity, and apoptosis. Results SBF2-AS1 was highly expressed in hepatocellular carcinoma cells (P<0.05). SBF2-AS1 knockdown resulted in decreased proliferation and invasion of Bel7402 and SK-hep1 cells (P<0.05). After miR-372-3p knockdown, the proliferation capacity and invasion number of Bel7402 cells were significantly increased. However, the above results were reversed after SBF2-AS1 knockdown (P<0.05). In addition, miR-372-3p targeted CDK6 and inhibited its expression, although over-expressing SFB2-AS1 could reverse the above results (P<0.05). Over-expressing CDK6 could reverse the inhibition of over-expressing miR-372-3p on the proliferation and invasion of Bel7402 cells. Conclusion LncRNA SBF2-AS1 can positively regulate the expression of CDK6 through miR-372-3p. It can also influence the distribution of cell cycle and affect the proliferation and invasion abilities of hepatocellular carcinoma cells.

A neonatal intelligent regulation system based on the combination of mild hypothermia mattress and hyperbaric oxygen chamber: introduction to a patent / 中国当代儿科杂志

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common disease that affects brain function in neonates. At present, mild hypothermia and hyperbaric oxygen therapy are the main methods for the treatment of neonatal HIE; however, they are independent of each other and cannot be combined for synchronous treatment, without monitoring of brain function-related physiological information. In addition, parameter setting of hyperbaric oxygen chamber and mild hypothermia mattress relies on the experience of the medical practitioner, and the parameters remain unchanged throughout the medical process. This article proposes a new device for the treatment of neonatal HIE, which has the modules of hyperbaric oxygen chamber and mild hypothermic mattress, so that neonates can receive the treatment of hyperbaric oxygen chamber and/or mild hypothermic mattress based on their conditions. Meanwhile, it can realize the real-time monitoring of various physiological information, including amplitude-integrated electroencephalogram, electrocardiogram, and near-infrared spectrum, which can monitor brain function, heart rate, rhythm, myocardial blood supply, hemoglobin concentration in brain tissue, and blood oxygen saturation. In combination with an intelligent control algorithm, the device can intelligently regulate parameters according to the physiological information of neonates and give recommendations for subsequent treatment.

Role of lysosomal damage in senescence of SH-SY5Y cells induced by methylmercury and intervention of melatonin / 环境与职业医学

Background Methylmercury (MeHg) is a neurotoxin, and melatonin (MT) has a protective effect on the nervous system, but whether it can antagonize MeHg-induced nerve cell damage and the associated mechanism remain unknown. Objective Human neuroblastoma cells (SH-SY5Y cells) were used as research objects. A MeHg-induced SH-SY5Y cell senescence model was established to observe autophagy related protein, lysosomal number, and function changes, as well as potential intervention role and associated mechanism of MT. Methods (1) After SH-SY5Y cells were treated with different doses of MeHg (0, 0.125, 0.25, 0.5, 1, 2, and 4 μmol·L−1) for 48 h, the cell viability was detected using a cell viability detection kit (CCK-8 method) and the viability rate was calculated. Senescent cells were detected by an acidic senescence-associated-β-galactosidase (SA-β-gal) staining. (2) A MeHg dose of 0.5 μmol·L−1 that significantly induced senescence of SH-SY5Y cells was screened, and a half and a quarter of the dose (0.25 and 0.125 μmol·L−1) were used for the middle and low dose groups, respectively. (3) In the MT intervention experiments, SH-SY5Y cells were divided into four groups, including control group (0.1% DMSO), MeHg group (0.5 μmol·L−1 MeHg), MT group (1 mmol·L−1 MT), and MT intervention group (1 mmol·L−1 MT+0.5 μmol·L−1 MeHg). In the MT intervention group, cells were exposed to 0.5 μmol·L−1 MeHg for 48 h after 24 h of 1 mmol·L−1 MT pretreatment. (4) SA-β-gal staining was conducted to observe cell senescence; Western blotting for the expression levels of senescence-associated protein p16, autophagy-associated protein p62, LC3Ⅱ, and lysosomal-associated proteins LAMP1, LAMP2, and TFEB; Lyso-Tracker Red for the quantity of lysosomes; LysoSensor Green DND-189 for lysosomal pH changes; electron microscope for the morphological changes of lysosomes. Results The results of CCK-8 indicated that the viability rate of cells decreased with the increase of MeHg exposure concentration. Compared with the control group, the SA-β-gal positive cell ratio in the 0.5 μmol·L−1 MeHg group increased by 48% (P<0.01), p16, p62, as well as LC3Ⅱ protein expressions were significantly increased (P<0.05), LAMP1 and LAMP2 protein levels, as well as the fluorescence intensities of lysosomal red and green fluorescent probes decreased with the increase of MeHg concentration (P<0.05), and the volume of lysosomes increased under the electron microscope. Compared with the MeHg group, the expression of p16 protein was decreased in the 1 mmol·L−1 MT + 0.5 μmol·L−1 MeHg group and the SA-β-gal positive cell ratio was significantly decreased by 19% (P<0.05), the protein levels of p62 and LC3Ⅱ were significantly decreased, the LAMP1 and LAMP2 protein levels and the fluorescence intensities of lysosomal red and green fluorescent probes were increased respectively, the nuclear entry of TFEB was significantly increased, and the differences were statistically significant (P<0.05). Conclusion MeHg may cause cellular senescence by reducing the number of lysosomes and impairing lysosomal activity in SH-SY5Y cells, and MT may ameliorate MeHg-induced lysosomal abnormalities in SH-SY5Y cells, thereby intervening cell senescence.

Hashimoto's encephalopathy presenting with isolated cerebellar ataxia in 13 children / 中华儿科杂志

Objective: To analyze the clinical characteristics, treatment and prognosis of Hashimoto's encephalopathy presenting with isolated cerebellar ataxia in children. Methods: A retrospective analysis was performed on the clinical features, laboratory tests, neuroelectrophysiological examination, imaging, treatment and outcomes of 13 patients with Hashimoto's encephalopathy presenting with isolated cerebellar ataxia, who were admitted to the Department of Pediatric Neurology of Guangzhou Women and Children's Medical Center from January 2016 to May 2021. Results: Among the 13 cases, 6 were males and 7 were females. The onset age was 2.6 (2.0,3.3) years, 9 children had precursor infection or vaccination before the first course of disease. All the 13 children had gait abnormalities or unsteady sitting, 10 had intentional tremor, 6 had dysarthria, 3 had body tremor, 2 had nystagmus, 3 had fatigue, 3 had hypotonia, 2 had vomiting and 1 had irritability. Thyroglobulin antibody (TgAb) was 500.0 (298.9,587.2) kU/L and thyroid peroxidase antibody (TPOAb) was 621.9 (449.6,869.4) kU/L in 13 cases. Autoantibodies were positive in 9 cases, and cerebrospinal fluid leukocytosis was seen in 4 cases. Regarding electroencephalography result, 4 cases had background slowing and 1 case had occasional sharp waves. Among the 3 patients who had relapses, 1 had cerebellar atrophy shown on cranial magnetic resonance imaging (MRI) during the recurrence. All the patients received intravenous immunoglobulin (IVIG) and intensive methylprednisolone therapy during the first onset, followed by the disappearance of the symptoms, 1 patient had repeated episodes which was decreased after immunosuppressive treatment with Rituximab.Followed up for 25.0 (22.5,33.3) months after the last episode, 12 achieved complete remission and 1 had a wide base gait. Conclusions: Trunk ataxia is the common symptom of Hashimoto's encephalopathy presenting with isolated cerebellar ataxia in children.Children with cerebellar ataxia should be tested for TgAb and TPOAb to detect Hashimoto's encephalopathy, avoiding missed diagnosis and treatment delays; IVIG and intensive steroid therapy is effective, and immunosuppressive therapy for patients with multiple relapses could reduce the recurrence.

Association of IL-10 and TNF-α gene polymorphisms with hepatic echinococcus granulosus infection and necrosis / 中国医师杂志

Objective:To investigate the association between hepatic echinococcus granulosus infection and necrosis with gene polymorphism of interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α), and to identify the related factors at the gene level.Methods:A total of 106 patients with hepatic echinococcosis who underwent surgical treatment in the department of hepatobiliary surgery, People′s Hospital of Xinjiang Uygur Autonomous Region from January 2018 to December 2020 were selected. Patients with necrosis caused by hepatic echinococcus granulosus infection were selected as the observation group, and patients without necrosis caused by hepatic echinococcus granulosus infection were selected as the control group, with 53 cases in each group. The serum levels of IL-10 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). The polymorphisms of IL-10 (-592, -1082) and TNF-α (rsl800630) were detected by polymerase chain reaction (PCR). The levels of IL-10 and TNF-α and their gene polymorphisms were analyzed.Results:The levels of serum IL-10 and TNF-α in the observation group were significantly higher than those in the control group (all P<0.05); There was significant difference in genotype and allele frequency of IL-10 (-592, -1082) and TNF-α (rsl800630) (all P<0.05). The serum IL-10 level of CC genotype patients with IL-10 gene -592C/A locus in the observation group was higher than that of CA+ AA genotype patients, with statistically significant difference ( P<0.05). The serum IL-10 level in patients with TT genotype at -1082T>A of IL-10 gene in the observation group was higher than that in patients with TA+ AA genotype, with statistically significant difference ( P<0.05). The serum TNF-α level in patients with CC genotype at rsl800630C/A locus of TNF-α gene in the observation group was higher than that in patients with CA+ AA genotype, with statistically significant difference ( P<0.05). Conclusions:The changes of IL-10 (-592, -1082) and TNF-α (rsl800630) gene polymorphisms may be associated with hepatic echinococcus granulosus infection and necrosis.

Factors influencing neurodevelopmental disorders in children with SCN8A-related early-onset epilepsy: a follow-up study of 21 cases / 中华实用儿科临床杂志

Objective:To explore the influence factors of neurodevelopmental disorders in children with SCN8A-related early-onset epilepsy through analyzing their clinical characteristics and following up their neurodeve-lopmental status. Methods:A retrospective analysis was carried out on 21 children (13 males and 8 females, the age ranged from 4 months to 8 years, average 31.6 months)with SCN8A-related early-onset epilepsy treated in Guangzhou Women and Children′s Medical Center and Kunming Children′s Hospital between January 2017 and February 2021.All patients underwent whole-exome sequencing and Sanger sequencing.The pathogenicity was estimated according to the American College of Medical Genetics and Genomics guidelines.The clinical data of all patients were also collected, including the age of onset of the disease, forms of seizures, seizure frequency, neurological development at onset, electroencephalogram (EEG) and brain magnetic resonance imaging (MRI). Besides, the patients were followed up to acquire the effect of sodium channel blockers after the onset of seizures, the process or improvement of neurodeve-lopment, EEG evaluation and neurodevelopmental outcomes.Patients were grouped based on data analysis results.The Fisher′s exact test was conducted to measure the effect of various factors on the neurodevelopmental process and outcome, and corresponding coe-fficients were calculated. Results:The average onset age of 21 patients was 0-9 months.The follow-up duration was 4 months-8 years.Three cases died.Sixteen cases (76.2%) had early infantile epileptic encephalopathy (EIEE), 5 cases (23.8%) had epilepsy without encephalopathy, and 1 case had benign infantile epilepsy.Fourteen cases (66.7%) belonged to drug resistant epilepsy.Only one child showed normal neurodevelopment.Eleven children showed delayed neurodevelopment, but improvement was observed.Nine children were retrogressed and stagnated in terms of neurodevelopment.Small age at onset ( Fisher=9.517, P=0.020, r=0.571), high seizure frequency ( Fisher=10.512, P=0.003, r=0.572), EEG background ( Fisher=10.512, P=0.003, r=0.572), epileptic discharges ( Fisher=8.288, P=0.008, r=0.542), and EEG changes before and after treatment ( Fisher=10.437, P=0.009, r=0.586) were important factors affecting the neurodevelopmental process.Neurodevelopmental outcome was normal in only 1 case, 1 child belonged to mild mental retardation (MR), 7 children belonged to moderate MR, 3 children belonged to severe MR, and 9 children belonged to profound MR.Statistical analysis indicated that the clinical phenotype ( Fisher=10.059, P=0.004, r=0.739) and drug resistance ( Fisher=13.706, P=0.001, r=0.640) were significantly correlated with neurodevelopmental outcomes.However, the forms of seizures, EEG findings at onset and mutation sites were not related to neurodevelopmental disorders. Conclusions:Most children with SCN8A-related early-onset epilepsy are accompanied with neurodevelopmental retardation of varying degrees.Epileptic encephalopathy and poor response to drug treatment will lead to severe neurodevelopmental disorders.

Effect of sciadopitysin on sodium arsenite-induced senescence of rat hippocampal neurons / 环境与职业医学

Background In addition to the typical signs of skin damage, long-term arsenic exposure is often accompanied by signs and symptoms of neurobehavioral abnormalities. Objective To investigate potential intervention effect of sciadopitysin on senescence of neurons induced by sodium arsenite in rats and possible underlying mediating effect of cell cycle-related transcription factor E2F1. Methods SH-SY5Y cells were treated with 4 μmol·L−1 sodium arsenite for 24 h and intervened with 50 μg·mL−1 Ginkgo biloba extract (EGb761) or four major biflavonoids in Ginkgo biloba leaves (isoginkgetin, bilobetin, sciadopitysin, and ginkgetin) for 24 h respectively. Then, cell viability was measured by CCK-8 assay. Thirty-two 180-200 g SPF rats were randomly divided into a control group, an arsenic treatment group (10 mg·L−1), a Ginkgo biloba extract intervention group (10 mg·kg−1), and a sciadopitysin intervention group (10 mg·kg−1), 8 rats in each group, half male and half female. The rats were treated with sodium arsenite by free drinking water for 3 consecutive months, and the intervention treatment was conducted after 2 months of poisoning with drug intake by gavage for 1 month. HE staining was used to detect structural changes in the hippocampus, while Nissl's staining was used to detect changes in hippocampal morphology and neuron numbers. Moreover, senescence-associated β galactosidase (SA-β-gal) staining and Western blotting were used to detect senescence of hippocampal neurons and the expression level of E2F1, respectively. Results Compared to the arsenic treatment group, EGb761 and the four biflavonoids in Ginkgo biloba leaves effectively antagonized the inhibitory effect of sodium arsenite on cell viability (all Ps＜0.05), and sciadopitysin showed better restoration of cellular viability than Ginkgo biloba extract (P＜0.05). The results of HE staining and Nissl's staining showed that the hippocampal neurons in the arsenic treatment group were reduced in cell count and the synaptic structure was abnormal, with swelling, nuclear shrinkage, and vacuole, compared with the control group. The results of SA-β-gal staining showed that the number of senescent cells in the arsenic treatment group (15.75±3.01) was significantly increased compared with the control group (2.88±0.84) (P＜0.05); the numbers of senescent cells in the Ginkgo biloba extract group (9.38±1.92) and the sciadopitysin treatment group (7.75±2.38) were significantly decreased compared with the arsenic treatment group (all Ps＜0.05). The results of Western blotting showed that compared with the control group, the expression of E2F1 protein in hippocampus of the arsenic treatment group was significantly decreased (1.00±0.17 vs. 0.65±0.19, P<0.05); compared with the arsenic treatment group, the protein expression level of E2F1 in hippocampus of the sciadopitysin treatment group (0.89±0.18) was significantly recovered (P<0.05); compared with Ginkgo biloba extract (0.68±0.19), sciadopitysin had a better recovery effect on E2F1 expression level (0.89±0.18) (P＜0.05). The results of correlation analysis showed that the E2F1 protein expression level was negatively correlated with the positive rate of SA-β-gal staining in hippocampal neurons (r=−0.518, P＜0.05). Conclusion Sciadopitysin is an effective component of Ginkgo biloba extract. It can effectively inhibit the senescence of hippocampal neurons induced by sodium arsenite, and E2F1 may play an important mediating role.

Analysis and future prospect of State Science and Technology Awards in the medical fields from 2000 to 2020 / 中华医学科研管理杂志

Objective:By analyzing State Science and Technology Awards in the medical fields from 2000 to 2020, this paper aims to provide possible references for the development, transformation and application of scientific and technological achievements under the context of new evaluation mechanism, to further improve the effectiveness of scientific research management.Methods:Accessing in to the website of National Office For Science & Technology Awards to obtain information of Science & Technology Awards in the field of Medicine, analyze and characterize the different types of awarded scientific and technological achievements.Results:The awarded medical achievements in the past 21 years were mainly aimed at the common and frequently encountered diseases in China, with the most achievements related to cancer and tumor disease, followed by cardiovascular disease and infectious disease. Universities accounted the highest proportion of awards thus becoming the main force of medical scientific and technological innovation, while more balance was needed in regional and organizational distribution. The first prizes of State Natural Science Award and State Technological Invention Award are visibly vacant.Conclusions:Priorities should be given to foster original scientific and technological achievements, to train elite medical talent, to solve the regional imbalance of medical innovation strength and to develop high-tech medical enterprises with international competitiveness, thus solving major medical challenges.

Ganhai Weikang capsule in the treatment of functional dyspepsia: a prospective randomized, double-blind, placebo-controlled parallel clinical study / 中华消化杂志

Objective:To explore the efficacy and safety of Ganhai Weikang capsule (GWC) in the treatment of functional dyspepsia (FD).Methods:A randomized, double-blind, placebo-controlled parallel, multi-center, superiority clinical trial was conducted. From March 2018 to April 2020, totally 324 patients with dyspepsia symptoms, who were diagnosed as chronic non-atrophic gastritis by endoscopy and pathology and met the Rome Ⅳ diagnostic criteria for FD from 7 top hospitals were enrolled, including the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Heilongjiang Hospital of Traditional Chinese Medicine, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Qilu Hospital of Shandong University, the First Affiliated Hospital of Zhejiang University, Beijing Hospital of Traditional Chinese Medicine of Capital Medical University and the Third Xiangya Hospital of Central South University. The patients were randomly divided into the GWC group and the placebo group according to the ratio of 1∶1. The patients of GWC group were given GWC and the patients of placebo group were given GWC capsule simulant. The patients of both groups orally took capsules before meals, 2.4 g each time and 3 times per day, and the course of treatment was 4 weeks. The main efficacy index was the total clinical effective rate after 4 weeks, and the secondary efficacy index was the changes of clinical symptom scores of upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety. The safety index included laboratory tests and adverse events. Chi-square test and Wilcoxon rank sum test were used for statistical analysis.Results:A total of 320 FD patients were enrolled in the full analysis set (FAS), which included 161 cases in GWC group and 159 cases in placebo group. A total of 298 cases were in the per-protocol set (PPS), 149 cases each in GWC group and placebo group. The results of FAS and PPS both showed that the total clinical effective rates of the GWC group were higher than those of the placebo group (84.5%, 136/161 vs. 44.0%, 70/159 and 83.9%, 125/149 vs. 46.3%, 69/149), and the differences were statistically significant ( χ2=57.07 and 46.32, both P<0.001). In addition, the differences of the total score of main symptoms and each symptom (upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety) before and after treatment of GWC group were all higher than those of the placebo group (FAS: 10 (7, 14) vs. 5 (3, 11); 3 (2, 4) vs. 2 (0, 3); 2 (0, 4) vs. 1 (0, 3); 3 (1, 4) vs. 2 (1, 3); 2 (0, 4) vs. 1 (0, 3). PPS: 10 (7, 13) vs. 5 (3, 11); 3 (2, 4) vs. 2 (0, 3); 2 (0, 4) vs. 1 (0, 2); 3 (1, 4) vs. 2 (1, 3); 2 (0, 4) vs.1 (0, 3)), and the differences were statistically significant (FAS: Z=5.80, 5.91, 3.19, 3.72 and 3.30; PPS: Z=5.14, 5.11, 2.86, 3.21 and 2.84; all P<0.01). The results of FAS and PPS indicated that the improvement rates of main symptoms and each symptom (upper abdominal pain, upper abdominal burning, postprandial fullness and early satiety) of GWC group were all higher than those of the placebo group (FAS: 77.8% (54.6%, 91.3%) vs. 42.9% (28.6%, 61.5%); 100.0% (60.0%, 100.0%) vs. 50.0% (25.0%, 60.0%); 100.0% (50.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 71.4% (33.3%, 100.0%) vs. 41.4% (25.0%, 66.7%); 100.0% (50.0%, 100.0%) vs. 50.0% (20.0%, 100.0%). PPS: 77.8% (54.2%, 89.5%) vs. 44.0% (28.6%, 65.0%); 100.0% (60.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 100.0% (50.0%, 100.0%) vs. 50.0% (25.0%, 100.0%); 71.4% (33.3%, 100.0%) vs. 46.4% (25.0%, 66.7%); 100.0% (50.0%, 100.0%) vs. 50.0% (20.0%, 100.0%)), and the differences were statistically significant (FAS: Z=8.60, 7.72, 4.98, 4.24 and 5.61; PPS: Z=7.90, 7.03, 4.49, 3.88 and 4.83; all P<0.001). After 2 weeks of treatment, the differences of the total score of main symptoms and score of each symptom (upper abdominal pain, upper abdominal burning and early satiety) before and after treatment of GWC group were all higher than those of the placebo group (5.0 (3.0, 8.0) vs. 4.0 (2.0, 6.0); 2.0 (1.0, 2.0) vs. 2.0 (0.0, 2.0); 1.5 (0.0, 2.0) vs. 1.0 (0.0, 2.0); 1.5 (0.0, 2.0) vs. 1.0 (0.0, 2.0)), and the differences were statistically significant ( Z=2.95, 3.44, 2.43 and 2.79, all P<0.05). There was no significant difference in the incidence of adverse events between the GWC group and the placebo group (0.6%, 1/163 vs. 0, 0/159). Conclusion:The clinical total effective rate of GWC in the treatment of FD is superior to that of placebo and it has good safety.

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.

Effect of hot spring bathing on rheumatoid related indicators and joint pain / 上海预防医学

Objective To observe the intervention effect of typical hot spring bathing in Guizhou province on joint pain, serum anti-keratin antibody(AKA), anti-perinuclear factor antibody(APF)and anti-cyclic citrullinated peptide antibody(CCP). Methods A total of 160 people with joint pain symptoms from five typical hot spring areas in Guizhou province were selected as the subjects. They were treated with hot spring bathing intervention for 4 weeks, once a day, 5 times a week, 40 to 50 minutes each time. According to the evaluation index of physiotherapy natural mineral water in the Code for Geological Exploration and Evaluation of Natural Warm Mineral Water Resources(GB/T 13727-2016)and geological types, the five typical hot springs were divided into three different types, namely water temperature type hot springs(water temperature > 36 ℃), metasilicate type hot springs(metasilicate > 50 mg/L)and warm mineral spring type hot springs(total dissolved solids > 1 000 mg/L). WHO pain grading standard was used to score the degree of joint pain before and after hot spring bathing intervention. Serum APF, AKA and CCP antibodies were detected by ELISA kit before and after hot spring bathing. Results The joint pain score of the subjects was 2.60±0.60, and the joint pain score of the total population decreased after intervention(0.61±0.57, P < 0.05). Before intervention, the joint pain scores of water temperature type, metasilicic acid type and warm mineral spring type were 2.78±0.96, 1.98±1.15 and 3.31±0.57, respectively. After intervention, the scores of joint pain of the three kinds of hot spring bathing patients all decreased(P < 0.05), and were 0.50±0.65, 0.48±0.74 and 0.85±0.90, respectively. Before intervention, AKA(ng/L)and CCP(μg/mL)antibody levels of the observed subjects were 34.89±16.06 and 107.58±10.40, respectively, which significantly decreased after intervention(both P < 0.05), namely 26.06±10.68 and 102.93±6.01, respectively. AKA(ng/L)was 35.04±20.01 before intervention, but decreased significantly after intervention(26.61±7.54, P < 0.05). AKA(ng/L)and CCP(μg/mL)were 31.09±17.26 and 106.51±10.13 before intervention, respectively. After intervention, the above two antibody indexes significantly decreased(all P < 0.05)to 24.53±13.98 and 98.57±5.68, respectively. Before intervention, the AKA(ng/L), APF(ng/mL)and CCP(μg/mL)antibody levels were 38.40±8.66, 349.46±118.43 and 104.96±9.66, respectively. After intervention, the above three antibody indexes significantly decreased(all P < 0.05). The values were 34.00±7.55, 269.38±127.55 and 101.65±3.04, respectively. Conclusion The typical hot spring bathing intervention in Guizhou province can relieve the symptoms of joint pain, and the three types of hot springs can reduce the levels of AKA, APF and CCP antibodies to different degrees, and the warm mineral spring type of hot spring is better than the other types of hot spring.

Analysis of the effect of hot spring bathing on serum melatonin levels and its association with sleep and anxiety / 上海预防医学

Objective To explore the improvement effect of typical hot spring bathing on sleep and anxiety and its correlation with serum melatonin level in Guizhou province. Methods Five typical characteristic hot springs in Guizhou were selected according to the geological type of hot spring water. A total of 226 residents in these areas were selected for the survey and the self-rating scale of sleep(SRSS)and the self-rating anxiety scale(SAS)were used to measure their scores before and after hot spring bathing, and the correlation between the changes of SRSS and SAS scores and the serum melatonin levels were analyzed. Results The SRSS and SAS scores of the respondents after hot spring bathing were lower than before, and the difference was statistically significant(P < 0.05). Serum melatonin levels after hot spring bathing were significantly higher than before(P < 0.05), and there was a negative correlation between the changes of SRSS and SAS scores and serum melatonin levels(P < 0.05). Conclusion Typical hot springs in Guizhou Province can significantly improve the sleep quality and anxiety state, which are related to the elevation of serum melatonin level.

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.

Ameliorative effect of hot spring bathing on the elevation of blood lipid in population / 上海预防医学

Objective To explore the effect of typical hot spring bathing of Guizhou Province on dyslipidemia, which could provide scientific basis for clarifying the physiotherapy effect of hot springs. Methods The typical hot spring sites of three main types(hydrothermal hot spring, warm mineral hot spring and metasilicate hot spring)in Guizhou Province were selected as investigation sites. 189 residents with hyperlipidemia near the investigation sites were selected as subjects and were treated with hot spring baths for 4 weeks, once a day, 5 times a week and 40-50 minutes each time. The age and gender distribution of the subjects were obtained by a questionnaire. The levels of TC, TG, LDL-C and HDL-C in serum were measured by automatic biochemical analyzer at baseline and at the end of hot spring baths. The differences of the three kinds of hot spring baths on improvement rate of dyslipidemia, the changes of abnormal blood lipid indexes and their improvement rates were compared. Results After baths of hydrothermal hot springs, warm mineral hot springs and metasilicate hot springs, the improvement rates of abnormally elevated lipids were 15.6%, 40.4% and 47.9%, respectively. The improvement rates of abnormally elevated lipids after baths of warm mineral hot springs and metasilicate hot springs were significantly higher than that after hydrothermal spring baths(all P < 0.05). Compared with before hot spring bathing, the levels of TC, TG, LDL-C and non-HDL-C in serum significantly decreased in all three kinds of hot springs. Moreover, the degree of decrease of TG in serum and the improvement rate of abnormal TG after baths of warm mineral spring and metasilicate hot spring were significantly higher than that after hydrothermal spring baths. The degree of decrease of LDL-C in serum and the improvement rate of abnormal LDL-C after baths of metasilicate hot spring were significantly higher than that after baths of hydrothermal spring and warm mineral spring(all P < 0.05). Conclusion The three types of typical hot spring baths in Guizhou Province can mitigate the elevation of blood lipid. Compared with hydrothermal spring, warm mineral spring and metasilicate hot spring may have better improvement effect on blood lipid elevation due to their more significant improvement effect on abnormal elevation of TG and LDL-C in serum.

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.

Overview of study of the physiotherapy efficacy of typical hot springs in Guizhou Province / 上海预防医学

To implement the Guizhou Provincial Party Committee and the Provincial Government's strategic goal of building a"Chinese Hot Spring Province"in an all-round way, promote the development of Guizhou's"big health, big tourism, big poverty alleviation"and other industries, and enhance the development and utilization of Guizhou hot springs and their health and wellness value. With the support of the provincial Geological Prospecting Fund project Guizhou Province Physiotherapy Hot Springs(Geothermal Water)Survey and Evaluation, Guizhou Medical University was responsible for completing the topic"Study on the Physiotherapy Efficacy of Typical Hot Springs in Guizhou Province". Here, the background, study and design plan, quality control, and features and limitations of this project are briefly introduced.

Analysis of lumbosacral sagittal balance parameter variation in minimally invasive transforaminal lumbar interbody fusion with real-time 3D navigation techniques / 中国骨伤

OBJECTIVE@#To explore the dynamic changes of lumbosacral sagittal parameters after real-time three-dimensional navigation assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and traditional open TLIF for treatment of lumbar degenerative disease.@*METHODS@#The clinical data of 61 patients with lumbar degenerative disease underwent single-segment surgery from September 2017 to September 2019 were retrospectively analyzed. Among them, 31 cases underwent MIS-TLIF with 3D navigation techniques (MIS-TLIF group) and another 30 cases underwent conventional open TLIF (traditional open TLIF group). The basic information, operative time and intraoperative blood loss were collected. The sagittal radiologic parameters were measured before surgery and 3 months after surgery, including lumbar lordosis (LL), segmental lordosis (SL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), anterior disc height (ADH), posterior disc height(PDH).And the average disc height(DH) and pelvic incidence to lumbar lordosis mismatch (PI-LL) were calculated.@*RESULTS@#Operative time and intraoperative blood loss in MIS-TLIF group were significantly less than in traditional open TLIF group(@*CONCLUSION@#Real-time navigation-assisted MIS-TLIF and traditional open TLIF can recover DH in a short term for lumbar degenerative diseases, improve LL and PI-LL, and make the arrangement of the sagittal plane of the lumbosacral region more coordinated after surgery. But only the navigation assisted MIS -TLIF can significantly improve SL. Compared with traditional open TLIF, real-time navigation assisted MIS-TLIF in the treatment of degenerative lumbar diseases has the advantages of short operation time and less intraoperative bleeding.

Meso-scale Discovery Assay Detects the Changes of Plasma Cytokine Levels in Mice after Low or High LET Ionizing Irradiation / 生物医学与环境科学（英文）

Objective@#To obtain precise data on the changes in the levels of 29 cytokines in mice after high or low linear energy transfer (LET) irradiation and to develop an accurate model of radiation exposure based on the cytokine levels after irradiation.@*Methods@#Plasma samples harvested from mice at different time points after carbon-ion or X-ray irradiation were analyzed using meso-scale discovery (MSD), a high-throughput and sensitive electrochemiluminescence measurement technique. Dose estimation equations were set up using multiple linear regression analysis.@*Results@#The relative levels of IL-6 at 1 h, IL-5 and IL-6 at 24 h, and IL-5, IL-6 and IL-15 at 7 d after irradiation with two intensities increased dose-dependently. The minimum measured levels of IL-5, IL-6 and IL-15 were up to 4.0076 pg/mL, 16.4538 pg/mL and 0.4150 pg/mL, respectively. In addition, dose estimation models were established and verified.@*Conclusions@#The MSD assay can provide more accurate data regarding the changes in the levels of the cytokines IL-5, IL-6 and IL-15. These cytokines could meet the essential criteria for radiosensitive biomarkers and can be used as radiation indicators. Our prediction models can conveniently and accurately estimate the exposure dose in irradiated organism.