Clinical research progress on corticotomy and modified techniques for accelerating orthodontic tooth movement / 口腔疾病防治

@#Adjunctive interventions for accelerating orthodontic tooth movement have been a hot topic of interest in orthodontics. Prolonged orthodontic treatment is often associated with multiple potential complications, such as decalcification, caries, root resorption, and gingival inflammation. Therefore, applying adjunctive interventions that accelerate orthodontic tooth movement and reduce the duration of orthodontic treatment can provide patients with numerous benefits that are of profound clinical significance. Currently, adjunctive interventions for accelerating orthodontic tooth movement can be divided into two main categories: surgical and nonsurgical. Surgical interventions, represented by corticotomy and modified corticotomy procedures, are the most common in clinical practice and can minimize the treatment duration, augment alveolar bone, and expand the range of orthodontic tooth movement. However, these procedures are inevitably traumatic and have many risks and limitations that prevent them from being widely used in clinical practice. In recent years, multiple modified corticotomy techniques, such as corticision, piezocision, micro-osteoperforation, and discision, have been proposed; these techniques can reduce soft and hard tissue damage and the incidence of postoperative complications and are relatively easy to perform in the clinic. Corticotomy and other improved surgical techniques can shorten the duration of orthodontic treatment to a certain extent and promote the recovery of periodontal health with no adverse effects on periodontal, dental, or pulp tissues. However, in clinical application, several potential side effects (such as periodontal tissue damage, root resorption, loss of pulp vitality, etc) and shortcomings need further research with long-term follow-up.

Mechanism of Yishen Tonglong Decoction inhibiting TLR4/p38 MAPK/NF-κB signaling pathway against prostate cancer via upregulating miR-145-5p / 数字中医药（英文）

@#【Objective】 To investigate the mechanism of Yishen Tonglong Decoction (益肾通癃汤, YSTLD) inhibiting the toll-like receptor 4/p38 mitogen activated protein kinases/nuclear factor kappa-B (TLR4/p38 MAPK/NF-κB) signaling pathway against prostate cancer by up-regulating miR-145-5p. 【Methods】 miRNA microarray technology was used to detect the changes of miRNA expression profile in prostate cancer PC-3 cells treated with YSTLD, and miRNAs with marked differences in miRNA microarray results were screened and validated by real-time polymerase chain reaction (qRT-PCR). Lentiviral transfection of miR-145-5p into prostate cancer PC-3 cells, Cell Counting Kit-8 (CCK8) assay, and scratch assay were adopted to detect the effects of miR-145-5p on prostate cancer PC-3 cell proliferation and migration. qRT-PCR and Western blot were employed to detect the effects of miR-145-5p on TLR4/p38 MAPK/NF-κB signaling pathway and the expression levels of apoptosis-related genes caspase3, tumor necrosis factor-α (TNF-α), Bax, and Bcl-2. qRT-PCR and Western blot were used to detect the effects of serum containing YSTLD on miR-145-5p, TLR4/p38 MAPK/NF-κB signaling pathway, and the expression levels of apoptosis-related genes caspase3, TNF-α, Bax, and Bcl-2. 【Results】 The expression levels of 35 miRNAs in prostate cancer PC-3 cells treated with YSTLD were significantly different from those in the control group, with miR-145-5p being the most significantly different; qRT-PCR validation revealed that the miR-145-5p levels in prostate cancer PC-3 cells treated with YSTLD were significantly higher than those in the DMSO control group (P < 0.05). After lentiviral transfection of miR-145-5p into prostate cancer PC-3 cells, miR-145-5p was found to inhibit the proliferation and migration of prostate cancer PC-3 cells. Overexpression of miR-145-5p up-regulated expression levels of caspase3, TNF-α, and Bax mRNA, and down-regulated expression levels of p38 MAPK, p65 NF-κB, and Bcl-2 mRNA in prostate cancer PC-3 cells (P < 0.05), while up-regulated caspase3 protein expression levels in prostate cancer PC-3 cells and down-regulated expression levels of TLR4, p38 MAPK, and p65 NF-κB protein (P < 0.05). Serum containing YSTLD could up-regulate the expression levels of caspase3, TNF-α, and Bax mRNA, and down-regulate the mRNA expression levels of p38 MAPK, p65 NF-κB, Bcl-2, and TNF receptor-associated factor 1 (TRAF1) in prostate cancer PC-3 cells after intervening prostate cancer PC-3 cells (P < 0.05). Simultaneously, it up-regulated the expression levels of caspase3 protein and down-regulated the protein expression levels of TLR4, p38 MARK, p65 NF-κB, and TRAF1 in prostate cancer PC-3 cells (P < 0.05). 【Conclusion】 YSTLD can promote apoptosis of prostate cancer PC-3 cells by up-regulating the expression level of miR-145-5p and inhibiting TLR4/p38 MAPK/NF-κB signaling pathway, which may be an important mechanism of YSTLD against prostate cancer.

Diagnostic value of nasal nitric oxide for children with primary ciliary dyskinesia / 中华儿科杂志

Objective: To evaluate the value of nasal nitric oxide (nNO) measurement as a diagnostic tool for Chinese patients with primary ciliary dyskinesia (PCD). Methods: This study is a retrospective study. The patients were recruited from those who were admitted to the respiratory Department of Respiratory Medicine, Children's Hospital of Fudan University from March 2018 to September 2022. Children with PCD were included as the PCD group, and children with situs inversus or ambiguus, cystic fibrosis (CF), bronchiectasis, chronic suppurative lung disease and asthma were included as the PCD symptom-similar group. Children who visited the Department of Child health Care and urology in the same hospital from December 2022 to January 2023 were selected as nNO normal control group. nNO was measured during plateau exhalation against resistance in three groups. Mann-Whitney U test was used to analyze the nNO data. The receiver operating characteristic of nNO value for the diagnosis of PCD was plotted and, the area under the curve and Youden index was calculated to find the best cut-off value. Results: nNO was measured in 40 patients with PCD group, 75 PCD symptom-similar group (including 23 cases of situs inversus or ambiguus, 8 cases of CF, 26 cases of bronchiectasis or chronic suppurative lung disease, 18 cases of asthma), and 55 nNO normal controls group. The age of the three groups was respectively 9.7 (6.7,13.4), 9.3 (7.0,13.0) and 9.9 (7.3,13.0) years old. nNO values were significantly lower in children with PCD than in PCD symptom-similar group and nNO normal controls (12 (9,19) vs. 182 (121,222), 209 (165,261) nl/min, U=143.00, 2.00, both P<0.001). In the PCD symptom-similar group, situs inversus or ambiguus, CF, bronchiectasis or chronic suppurative lung disease and asthma were significantly higher than children with PCD (185 (123,218), 97 (52, 132), 154 (31, 202), 266 (202,414) vs. 12 (9,19) nl/min,U=1.00, 9.00, 133.00, 0, all P<0.001). A cut-off value of 84 nl/min could provide the best sensitivity (0.98) and specificity (0.92) with an area under the curve of 0.97 (95%CI 0.95-1.00, P<0.001). Conclusions: nNO value can draw a distinction between patients with PCD and others. A cut-off value of 84 nl/min is recommended for children with PCD.

Empirical analysis on lumbar disc herniation treated with "sinew-bone three needling technique" of Chinese medicine / 中国针灸

The paper presents professor WU Han-qing's experience in treatment of lumbar disc herniation (LDH) with "sinew-bone three needling technique" of Chinese medicine. Based on the theory of meridian sinew, the points are located by "three-pass method" in terms of the distribution of meridian sinew and syndrome/pattern differentiation. The cord-like muscles and adhesion are relieved by relaxing technique to work directly on the affected sites and alleviate the local compression to the nerve root. The needle technique is operated flexibly according to the affected regions involved, due to which, the needling sensation is increased while the safety ensured. As a result, the meridian qi is enhanced, the mind and qi circulation is regulated; and the clinical effect is improved.

Research progress on the role and mechanism of endothelial dysfunction in hyperhomocysteine-induced atherosclerosis / 生理学报

Hyperhomocysteinemia (HHcy) is considered to be an independent risk factor for cardiovascular diseases, but the molecular mechanisms underlying its pathogenesis are not fully understood. Endothelial dysfunction is a key initiating factor in the pathogenesis of atherosclerosis, which is commonly observed in almost all HHcy-induced vascular diseases. HHcy promotes oxidative stress, inhibits nitric oxide production, suppresses hydrogen sulfide signaling pathway, promotes endothelial mesenchymal transition, activates coagulation pathways, and promotes protein N-homocysteination and cellular hypomethylation, all of which can cause endothelial dysfunction. This article reviews the specific links between HHcy and endothelial dysfunction, and highlights recent evidence that endothelial mesenchymal transition contributes to HHcy-induced vascular damage, with a hope to provide new ideas for the clinical treatment of HHcy-related vascular diseases.

Analysis of expression and clinical significance of METTL7B in glioma tissues based on bioinformatics / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨甲基转移酶样蛋白7B（METTL7B）在胶质瘤组织中的表达及其与患者临床病理特征和预后的相关性。方法：基于CGGA数据库胶质瘤数据和GTEx数据库正常脑组织数据，分析METTL7B基因在胶质瘤与正常脑组织中的表达差异，并用GEPIA数据库数据和免疫组织化学染色法进行验证。用Kaplan-Meier生存分析、单因素Cox分析、多因素Cox分析及ROC曲线分析等评估METTL7B在胶质瘤患者预后中的价值，用CGGA数据库数据分析METTL7B表达与胶质瘤患者临床病理特征的相关性，用CIBERSORT及TIMER数据库进行肿瘤免疫细胞浸润分析，进行KEGG通路富集分析及GO功能富集分析，通过基因共表达分析确定与METTL7B相关的基因。结果：METTL7B在胶质瘤组织中明显上调（均P<0.05），METTL7B表达是胶质瘤患者独立的不良预后因素。METTL7B高表达与高龄（>41岁）、肿瘤分级增加、肿瘤复发或继发性肿瘤、IDH野生型、1p19q非共缺失以及肿瘤的恶性病理学有关联（均P<0.01）；METTL7B表达与B细胞、CD4+ T细胞、CD8+ T细胞、单核细胞、中性粒细胞、巨噬细胞、活化肥大细胞等免疫细胞有关联（均P<0.05）。KEGG通路富集及GO功能分析结果显示，肿瘤相关信号通路及多种免疫反应在METTL7B高表达表型中显著富集。基因共表达分析结果表明，METTL7B与TNFRSF12A、CHI3L1、EMP3表达呈正相关（r=0.807、0.804、0.783，均P<0.01），与ELFN2、REPS2、SHANK2表达呈负相关（r=-0.642、-0.627、-0.602，均P<0.01）。结论：METTL7B在胶质瘤组织中的表达上调是预后不良的指标，且与肿瘤免疫浸润相关。

Efficacy of the herbal pair, Radix Achyranthis Bidentatae and Eucommiae Cortex, in preventing glucocorticoid-induced osteoporosis in the zebrafish model / 中西医结合学报

OBJECTIVE@#In traditional Chinese medicine, the herbal pair, Radix Achyranthis Bidentatae (RAB) and Eucommiae Cortex (EC), is widely used to treat osteoporosis. Herein, we determined whether this herbal pair can be used to ameliorate glucocorticoid (GC)-induced osteoporosis (GIOP) and find its optimal dosage in zebrafish.@*METHODS@#The characteristics of the aqueous extract of RAB and EC were separately characterized using high-performance liquid chromatography. Osteoporosis was induced in 5-day post-fertilization zebrafish larvae by exposing them to 10 μmol/L dexamethasone (Dex) for 96 h. Seven combinations of different ratios of RAB and EC were co-administered. Treatment efficacy was determined by calculating zebrafish vertebral area and sum brightness, via alizarin red staining, and by detecting alkaline phosphatase (ALP) activity. Multiple regression analysis was conducted to test the optimal dosage ratio.@*RESULTS@#According to the Chinese Pharmacopoeia (2015), β-ecdysone (β-Ecd) is a major bioactive marker in RAB extract, while pinoresinol diglucoside (PDG) is the major marker in EC extract. Both of β-Ecd and PDG content values aligned with the Chinese Pharmacopoeia standards. Treatment with 10 μmol/L Dex reduced zebrafish vertebral area, sum brightness, and ALP activity, but RAB and EC attenuated these effects. Combining 50 µg/mL RAB and 50 µg/mL EC was optimal for preventing GIOP in zebrafish. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the mRNA expression of osteogenesis-related genes. A treatment of 10 μmol/L Dex decreased runt-related transcription factor 2 (Runx2), osteogenic protein-1 (OP-1), bone γ-carboxyglutamic acid-containing protein (BGLAP), and β-catenin levels. This effect was counteracted by RAB and EC co-treatment (P < 0.05). Additionally, the effect of using the two herbal extracts together was better than single-herb treatments separately. These results demonstrated that RAB and EC preserve osteoblast function in the presence of GC. The best mass ratio was 1:1.@*CONCLUSION@#RAB and EC herbal pair could ameliorate GC-induced effects in zebrafish, with 1:1 as the optimal dosage ratio.

Effects of excessive fluoride exposure on astrocytes and the expression of glial fibrillary acidic protein in vitro and in vivo / 中华地方病学杂志

Objective:To investigate the effects of excessive fluoride exposure on astrocytes and the expression of glial fibrillary acidic protein (GFAP), in vitro and in vivo. Methods:(1) In vivo experiment: 24 SPF SD rats, half male and half female, were randomly divided into control and fluoride exposed groups according to sex and body weight, 12 rats in each group. Rats were fed with < 1 mg/L and 50 mg/L sodium fluoride solution prepared by tap water for 6 months, respectively. The expression levels of GFAP protein in rat brain tissue were measured by immunofluorescence, immunohistochemistry and Western blotting. (2) In vitro experiment: adult (6-month-old) rat cortical astrocytes were extracted and cultured in primary culture (4 mmol/L sodium fluoride solution for 24 h), and the astrocytes were identified by immunofluorescence, and GFAP mRNA and protein expression levels were detected by real-time fluorescence quantitative PCR and Western blotting, respectively, and astrocytes apoptosis and calcium ion content were detected by flow cytometry. Results:(1) In vivo experiment: the results of immunofluorescence, immunohistochemistry and Western blotting showed that the GFAP protein expression level in brain tissue of rats exposed to fluoride was higher than that of control group (0.440 ± 0.200 vs 0.250 ± 0.120, t =-5.93, P = 0.027; 0.270 ± 0.020 vs 0.240 ± 0.050, t =-4.87, P = 0.040; 1.017 ± 0.001 vs 0.486 ± 0.006, t =-52.48, P = 0.001). (2) In vitro experiment: GFAP positive cells were identified as astrocytes by immunofluorescence; GFAP mRNA expression level was higher in fluoride exposed group than that of control group by real-time fluorescence quantitative PCR (2.780 ± 0.120 vs 0.134 ± 0.005, t =-37.84, P = 0.001). The Western blotting results showed that the GFAP protein expression level was higher in fluoride exposed group than that of control group (2.76 ± 0.10 vs 1.38 ± 0.05, t =-20.44, P = 0.002). Flow cytometry results showed that the apoptosis rate of astrocytes was higher in fluoride exposed group than that of control group (%: 55.0 ± 1.0 vs 3.5 ± 0.6, t =-10.28, P = 0.009) and the calcium ion content was lower than that of control group (%: 54 ± 9 vs 72 ± 13, t = 4.64, P = 0.043). Conclusion:Excessive fluoride exposure causes increased GFAP expression in astrocytes in vitro and in vivo, promotes apoptosis, and affects calcium signaling pathways.

Effect of 6 week neck eccentric training on neck function of college students / 中国学校卫生

Objective@#To investigate the effect of cervical eccentric training on neck function of college students, and to provide basis for cervical spondylosis prevention.@*Methods@#Fifty two students from a medical college in Shanxi Province were recruited. Participants were divided into the neck eccentric training intervention group and the control group according to the random number table method, after stratified by sex. The intervention group received training for 25 min each time, 3 times a week for 6 weeks, and the control group received neck health education. Neck circumference, strength, range of motion, endurance and head and neck posture were measured before and after intervention.@*Results@#The interaction of strength anterior flexion, extension left fiexion and right flexion was significant( F=34.25, 55.96, 56.49, 37.13, P <0.05). After 6 weeks, the strength of the intervention group was anterior flexion(65.37±18.64)N, extension(87.61±21.38)N, left flexion(55.80±12.04)N, right flexion(55.87±11.83)N. After 6 weeks, the strength of the control group were (45.69±9.25), (53.34±9.45), (41.60±6.96) and(42.20±9.92)N, which were significantly lower compared to the intervention group( t =4.82, 7.48, 5.21, 4.52, P <0.01). The interaction of motion of anterior flexion, extension, left flexion and right flexion were significant( F=11.62, 8.83, 8.29, 6.57, P <0.05). After 6 weeks, the motion of intervention group had anterior flexion(53.54±7.28)°, extension(57.42±7.37)°, left flexion(40.77±4.14)°, right flexion(85.12± 6.35 )°. The corresponding motion levels of the control group were(45.35±9.55)°,(50.85±7.56)°,(37.19±5.86)°,(76.15±7.86)°. The intervention group was significantly higher than the control group( t=3.48, 3.18, 2.54, 4.52, P <0.05). Main effects on time were observed in neck circumference, right flexion and left rotation motion, neck endurance and head extension angle( F =15.79, 13.94, 35.90, 10.17, 8.61, P <0.05).@*Conclusion@#Six week neck eccentric training can significantly improve neck strength and range of motion, as well as neck circumference, neck endurance and head forward posture.

Research progress of novel drug delivery system for STING agonist / 中国药理学通报

Stimulator of interferon genes(STING)is a key protein in cGAS-STING signaling pathway and plays an important role in immune response mediated by the exogenous or endogenous DNA.This review describes the biological function of STING, the process of cGAS-STING pathway, the classification and administration of STING agonists, and summarizes the currently reported drug delivery systems.The delivery of STING agonists through appropriate drug carriers can overcome the lack of difficult entry, easy enzymatic hydrolysis, short half-life and poor targeting, improve the body's innate and adaptive immunity, and enhance the therapeutic effect of drugs.In conclusion, this paper mainly reviews the research progress of drug delivery system for STING agonists to provide basis for the development of drug delivery system and promote the clinical transformation and application of STING agonists.

Associação entre vitamina D sérica e rinossinusite crônica: uma metanálise / Association between serum vitamin D and chronic rhinosinusitis: a meta-analysis

Resumo Introdução: A rinossinusite crônica é uma inflamação crônica altamente heterogênea do trato respiratório superior causada por uma disfunção imune nos seres humanos. Entretanto, a etiologia subjacente dessa doença ainda não foi bem estabelecida. Diversos estudos revelaram que anormalidades nos níveis séricos de vitamina D podem desempenhar um papel na fisiopatologia da doença. Objetivo: Fazer uma metanálise de estudos para comparar os níveis séricos de vitamina D entre pacientes com rinossinusite crônica e controles saudáveis e avaliar as potenciais associações do nível sérico de vitamina D com a ocorrência da doença. Método: Seguindo as diretrizes Prisma, bancos de dados relevantes, inclusive Pubmed, Web of Science, Embase e Cochrane Library, foram pesquisados desde a sua data de início até 1° de dezembro de 2018. A simetria do gráfico de funil (funnel plot symmetry) e o teste de Egger foram usados para detectar o viés da publicação. Os desfechos foram apresentados como diferença média ponderada e combinamos a diferença média ponderada e intervalos de confiança de 95% para estimar a diferença dos níveis séricos de vitamina D entre pacientes com rinossinusite crônica e os controles. O valor de I2 de Higgins foi usado para testar a heterogeneidade entre os estudos incluídos. Resultados: Dos 176 estudos que identificamos, apenas oito, que envolveram 337 pacientes com rinossinusite crônica e 179 controles saudáveis, preencheram os critérios e foram incluídos na metanálise. Em uma análise combinada de todos os estudos, a diminuição do nível sérico de vitamina D foi demonstrada na rinossinusite crônica (DMP = −7,80, IC95% −13,28 ± −2,31, p = 0,000). Análises de subgrupos com base no local do estudo (EUA vs. Não EUA), tipos de biomarcadores (25[OH]D3 vs. 25[OH]D) e desenho do estudo (retrospectivo vs. prospectivo) não explicaram a heterogeneidade. No entanto, o fenótipo da rinossinusite crônica (rinossinusite crônica com pólipos nasais vs. rinossinusite crônica sem pólipos nasais) pode explicar algum grau de heterogeneidade. Contudo, um nível sérico mais baixo de vitamina D foi observado em pacientes com rinossinusite crônica com pólipos nasais. Conclusão: Nossos achados indicam que o nível sérico de vitamina D pode estar associado à rinossinusite crônica, pois detectamos uma associação significante entre níveis séricos mais baixos de vitamina D em pacientes com rinossinusite crônica, especialmente na rinossinusite crônica com pólipos nasais. No entanto, mais estudos abrangentes são necessários para se chegar a conclusões abalizadas.

Prevalence of human soil-borne nematode infections in Yunnan Province: a cross-sectional study in 2015 / 中国血吸虫病防治杂志

Objective To investigate the current prevalence of human soil-borne nematode infections in Yunnan province, so as to provide the scientific evidence for formulating the soil-borne nematodiasis control strategy in the province. Methods In 2015, a total of 20 survey sites were sampled in 10 counties (cities) of Yunnan Province using the stratified cluster random sampling method. Stool samples were collected from all local permanent residents at ages of one year and older in each survey site, and the soil-borne nematode eggs were identified using the modified Kato-Katz technique and the egg number was counted. In addition, the hookworm species was identified using the filter-paperculture method, and Enterobius vermicularis eggs were detected using the cellophane tape method in children at ages of 3 to 6 years. Results A total of 5 067 residents received stool examinations, and 950 residents were detected with soil-borne nematode infections, with an overall prevalence rate of 18.75%. The prevalence of Ascaris lumbricoides, Trichuris trichura and hookworm was 7.52%, 8.47% and 9.02%, respectively. Among 446 children detected using the cellophane tape method, 5 children were detected with E. vermicularis infections. Among the 160 residents with hookworm infections, there were 139 residents with Necator americanus infections (86.88%), 16 with A. duodenale infections (10.00%) and 5 with mixed infections (3.12%). Mild A. lumbricoides (67.98%, 259/381), T. trichura (88.58%, 380/429) and hookworm infections (94.53%, 432/457) were predominant. Among the four ecological zones, the highest prevalence of human soilborne nematode infections was found in the East Tibet-South Sichuan Ecological Zone (31.79%), and among the 10 survey counties (cities), the greatest prevalence was seen in Gongshan Derung and Nu Autonomous County (50.13%), while the lowest prevalence was found in Ninglang Yi Autonomous County (0.40%). The prevalence of human soil-borne nematode infections was 5.67% (43/759), 26.67% (610/2 287) and 14.70% (297/2 021) in high-, moderate- and low-economic-level regions, respectively. There were no significant differences in the prevalence of human soil-borne nematode infections in terms of ecological regions, survey counties (cities) or economic development levels (χ2 = 342.20, 814.60 and 201.34, all P < 0.05). There was no significantdifference in the prevalence of human soil-borne nematode infections between male (18.21%, 441/2 422) and female residents (19.24%, 509/2 645) (χ2 = 0.89, P > 0.05), and soil-borne nematode infections were detected in residents at all age groups, with the greatest prevalence found in residents at ages of 1 to 9 years (25.88%). In addition, the highest prevalence of soil-borne nematode infections was seen in residents with the Dulong Ethnic Minority (82.09%), in preschool children (25.06%) and in illiterate residents (24.80%), and there was no age-, ethnicity-, occupation- or education level-specific prevalence of soil-borne nematode infections detected (χ2 = 46.50, 1 016.96, 36.33 and 52.43, all P < 0.05). Conclusions The prevalence of human soil-borne nematode infections remains high in Yunnan Province. The management of soil-borne nematodiasis requires to be reinforced among low-age children, farmers, old people and residents with low educations levels or ethnic groups.

Epidemiological characteristics and trends of stroke death in Hexi District of Tianjin from 2007 to 2019 / 上海预防医学

Objective:To analyze the epidemiological characteristics and trend of stroke death among registered residents in Hexi District of Tianjin from 2007 to 2019，and to provide scientific basis for evaluation of comprehensive prevention and control strategies and measures of stroke. Methods:All death monitoring data of the residents was collected and the crude mortality， standardized mortality and annual percent change （APC） of stroke were obtained by statistical treatment. Results:A total of 15 235 stroke deaths were reported in Hexi District of Tianjin from 2007 to 2019，with an average annual mortality rate of 144.59/105. The rate was higher in males than in females （169.02/105 in males and 121.04/105 in females， P<0.001）. The crude mortality rate showed an upward trend with the year （APC=1.51%， P<0.05）. The standardized mortality rate showed a downward trend （APC=-1.39%， P<0.05）. The crude mortality of ischemic stroke showed an upward trend with the year （APC=3.15%， P<0.01）， and the trend change in standardized mortality rate had no statistical significance. The crude mortality and standardized mortality of hemorrhagic stroke showed a downward trend，with the mortality rate decreased at 2.43% per year and the standardized mortality rate decreased at the 4.50% per year （all P<0.05）. Conclusion:Stroke is the main disease affecting the health of residents in Hexi District of Tianjin. Targeted measures should be taken to reduce the mortality of stroke. Stroke prevention and control should focus on winter and spring seasons， males， elderly people and patients with ischemic stroke.

Research Progress in Genetic Research of Fatigue / 中国实验方剂学杂志

Fatigue refers to the manifestation of disorders in the process of carrying out or maintaining random activities， which can be regarded as an independent disease or as a symptom in a variety of chronic diseases. The high incidence of fatigue has seriously affected people's physical and mental health， and the prevention and treatment of fatigue has become an important problem to be solved urgently. The pathogenesis of fatigue mainly includes energy consumpation， accumulation of metabolites， abnormal secretion of neurotransmitters， decline of mitochondrial function， dysfunction of hypothalamus pituitary adrenal axis， etc. At present， there is no unified understanding about the pathogenesis of fatigue at home and abroad. The gene research of fatigue is the current research frontier. Gene expression profiling provides a new method for the study of the mechanism of fatigue. The combination of gene chip technology and traditional Chinese medicine（TCM） theory is expected to bring a breakthrough in the study of the pathogenesis of fatigue. In the study of fatigue gene chip， messenger RNA（mRNA） and microRNA（miRNA） are the common research objects， but few explorations are focused on the gene expression rule of fatigue by a specific signaling pathway and the effective regulation targets of TCM for treating fatigue. In recent years， the dysfunction of reward and inhibition mechanism in the central nervous system has become a research hotspot. In particular， gamma amino butyric acid （GABA） and dopamine （DA） have attracted much attention as the main substances of inhibition and reward mechanism， respectively. GABA and DA are used as inhibition and reward mechanisms to maintain the balance， and the body will not feel fatigue. Once the balance is broken， the fatigue will be formed. At the same time， DA and GABA receptors can also regulate cyclic adenosine monophosphate signaling pathway（cAMP） to affect fatigue. The research on key genes in GABA/DA balance mechanism and related cAMP signaling pathway by gene chip technology is expected to reveal the pathogenesis of fatigue in depth. The gene chip method is used to detect the changes of key genes in GABA/DA pathway and the related cAMP signaling pathway in the fatigue population and the normal population， so as to further explore the pathogenesis of fatigue. In this paper， the key genes in GABA/DA balance mechanism and cAMP signaling pathway related to fatigue were summarized by using the review method， so as to provide the basis for further study on the pathogenesis of fatigue and effective prevention and treatment from the perspective of genetics.

Study on Therapeutic Effect and Related Mechanism of Fuyou Granule on Precocious Puberty in SD Female Rats / 中国实验方剂学杂志

Objective:To study the effect and related mechanism of Fuyou granule on danazol-induced precocious puberty model in rats. Method:Totally 21 cages of SD female rats were randomly divided into normal group， model group， Leuprorelin（0.1 g·kg^-1） and Fuyou mixture group（37.9 g·kg^-1）， and high-dose， mid-dose and low dose Fuyou granule<italic> </italic>groups（17.0，8.5，4.3 g·kg^-1）. Rats at 5 days of age were given a single subcutaneous injection of 300 μg danazol to establish the precocious puberty model. After 10 days of modeling， drug intervention was started. Vaginal opening was examined at the age of 20 days， and the gonadal development was observed by hematoxylin-eosin （HE） staining. The levels of serum luteinizing hormone （LH）， follicle-stimulating hormone （FSH） and estradiol （E₂） were determined by radioimmunoassay. The mRNA expressions of hypothalamic gonadotropin releasing hormone （GnRH）， Kiss-1， G protein-coupled receptor 54 （GPR54） were detected by Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， and the expression of GnRH cells in the hypothalamus was detected by immunohistochemistry. Result:Compared with the normal group， the vaginal opening of the model group was significantly earlier， and the uterus and ovarian coefficients were significantly increased （<italic>P</italic><0.05）， indicating that the danazol-induced precocious puberty model was successfully established. The expression levels of GnRH， Kiss-1， and GPR54 also increased significantly （<italic>P</italic><0.05）， indicating that the danazol model can activate the HPG axis in advance， thereby inducing precocious puberty<bold>. </bold>Compared with the model group， the mid-dose Fuyou granule group significantly delayed the time of vaginal opening （<italic>P</italic><0.01）， high-dose Fuyou granule group<italic> </italic>significantly reduced uterine wall thickness and uterine coefficient （<italic>P</italic><0.05，<italic>P</italic><0.01）， mid-dose group reduced ovarian coefficient and uterine wall thickness （<italic>P</italic><0.05）. All the three dosage groups of Fuyou granule significantly reduced the content of serum hormones E₂， LH and FSH （<italic>P</italic><0.05，<italic>P</italic><0.01）， reduced the expression levels of hypothalamic GnRH， Kiss-1 and GPR54 mRNA （<italic>P</italic><0.05）， and decreased the expression of GnRH cells （<italic>P</italic><0.05）. Conclusion:Fuyou granule can achieve therapeutic precocity by regulating the Kiss-1/GPR54 system and down-regulating the expression of GnRH to inhibit the activation of the HPG axis.

Serum antibody levels in COVID-19 patients six months after hospital discharge / 上海预防医学

ObjectiveTo investigate the level of serum antibodies in COVID-19 patients six months after discharge， and to provide data to evaluate the duration of IgM， IgG and neutralizing antibody titers in the patients. MethodsEnzyme-linked immunosorbent assay （ELISA） was used to determine the antibody levels of IgM and IgG， and the new coronavirus live virus neutralization test was used to detect the neutralizing antibodies in the plasma of 181 recovered patients. ResultsThe IgG positive rate was 92.27% （167/181） in COVID-19 patients six months after discharge， while the lgM positive rate was 28.18% （51/181）. Six months after hospital discharge， 117 recovered patients （64.64%） were positive for IgG antibodies and negative for IgM antibodies， indicating that they had produced stable antibodies. This result suggested that they had been infected with the new coronavirus （SARS-CoV-2） and were in the recovery stage. The positive detection rate of neutralizing antibodies was as high as 91.71%. ConclusionSix months after infection with SARS-CoV-2， IgG antibodies produced in the patients continue to exist， and the neutralizing antibodies maintain a high and stable level. Results of this study have important guiding significance for future research on the durability of new coronavirus antibodies.

Serum antibody levels in COVID-19 patients six months after hospital discharge / 上海预防医学

ObjectiveTo investigate the level of serum antibodies in COVID-19 patients six months after discharge， and to provide data to evaluate the duration of IgM， IgG and neutralizing antibody titers in the patients. MethodsEnzyme-linked immunosorbent assay （ELISA） was used to determine the antibody levels of IgM and IgG， and the new coronavirus live virus neutralization test was used to detect the neutralizing antibodies in the plasma of 181 recovered patients. ResultsThe IgG positive rate was 92.27% （167/181） in COVID-19 patients six months after discharge， while the lgM positive rate was 28.18% （51/181）. Six months after hospital discharge， 117 recovered patients （64.64%） were positive for IgG antibodies and negative for IgM antibodies， indicating that they had produced stable antibodies. This result suggested that they had been infected with the new coronavirus （SARS-CoV-2） and were in the recovery stage. The positive detection rate of neutralizing antibodies was as high as 91.71%. ConclusionSix months after infection with SARS-CoV-2， IgG antibodies produced in the patients continue to exist， and the neutralizing antibodies maintain a high and stable level. Results of this study have important guiding significance for future research on the durability of new coronavirus antibodies.

Non-invasive electrical neuromodulation techniques: analgesic effects and neural mechanisms / 生理学报

As non-pharmaceutical interventions, non-invasive electrical neuromodulation techniques are promising in pain management. With many advantages, such as low costs, high usability, and non-invasiveness, they have been exploited to treat multiple types of clinical pain. Proper use of these techniques requires a comprehensive understanding of how they work. In this article, we reviewed recent studies concerning non-invasive electrical peripheral nerve stimulation (transcutaneous electrical nerve stimulation and transcutaneous vagus/vagal nerve stimulation) as well as electrical central nerve stimulation (transcranial direct current stimulation and transcranial alternating current stimulation). Specifically, we discussed their analgesic effects on acute and chronic pain, and the neural mechanisms thereof. We then contrasted the four kinds of nerve stimulation techniques, pointing out limitations of existing studies and proposing directions for future research. With more extensive and in-depth research to overcome these limitations, we shall witness more clinical applications of non-invasive electrical nerve stimulations to alleviate patients' pain and ease the crippling medical and economic burden imposed on patients, their families, and the entire society.

Application of digital prosthesis in the repair of palatal fistula in rabbits / 中国组织工程研究

BACKGROUND: Digital impression technology has been widely used in the oral field. Compared with traditional impression technology, it is more convenient and accurate. OBJECTIVE: To explore the application of digital prosthesis for repairing palatal fistula in rabbits. METHODS: The rabbit models of palatal fistula were established by surgery. One month later, 10 rabbit models of palatal fistula were scanned by digital intraoral scanning system. The medical silicone rubber prosthesis for palatal fistula was manufactured by digital impression technology and digital design. After wearing the prosthesis, SUN LB, LAN YY, ZHOU HY, HUY. Application of digital prosthesis In me repair of palatal fistula In rabbits.  Zhongguo Zuzhi Gongcheng Yanjiu. 2020;24(14):2192-2196. DPI:10.3969/j.issn.2095-4344.2228 the accuracy, retention and sealing properties of the prosthesis were examined. The study was approved by the Laboratory Animal Ethical Committee of Hospital of Stomatology, Southwest Medical University. RESULTS AND CONCLUSION: After digital prosthesis repaired palatal fistula, the accuracy, retention and sealing properties of the prosthesis were good. To conclude, the digital prosthesis for palatal fistula repair by digital impression technology achieves accurate repair, and has certain clinical values.