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AIM: To systematically evaluate the efficacy of intense pulsed light(IPL)combined with meibomian gland expression(MGX)in the treatment of meibomian gland dysfunction(MGD)-related dry eye disease(DED).METHODS: Chinese and English databases such as Chinese national knowledge infrastructure(CNKI), Wanfang, VIP, CBM, ClinicalTrials, PubMed, Embase and Web of Science were searched, and clinical randomized controlled trials(RCTs)using IPL combined with MGX in the experimental group and MGX alone in the control group from January 2017 to September 2022 were included. Six outcome indicators including clinical efficacy, ocular surface disease index(OSDI)score, break-up time(BUT), corneal fluorescein staining(CFS)score, tear meniscus height(TMH)and meibomian gland yielding secretion score(MGYSS)were Meta analyzed by Review Manager 5.3 and Stata 14 software.RESULTS: A total of 15 RCTs were included, with 1 345 patients with MGD-related dry eye. Meta-analysis results showed that the treatment of MGD-related dry eye in the experimental group improved better clinical efficacy(OR=4.95, 95%CI: 2.76～8.90, Z=5.35, P<0.00001), BUT(SMD=1.26, 95%CI: 0.84～1.69, Z=5.78, P<0.00001), TMH(SMD=0.37, 95%CI: 0.15～0.59, Z=3.33, P=0.0009), and reduced OSDI scores(SMD=-0.86, 95%CI: -1.44～-0.27, Z=2.85, P=0.004)as well as MGYSS(SMD=-2.43, 95%CI: -4.31～-0.54, Z=2.52, P=0.01)than the control group. However, there was no statistically significant difference in CFS scores(SMD=-0.19, 95%CI: -0.46～0.07, Z=1.43, P=0.15).CONCLUSION: IPL combined with MGX in the treatment of MGD related dry eye can increase the overall effective rate and improve the symptoms and signs of patients with MGD related dry eye better than MGX alone.
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ObjectiveTo explore the amelioration of cognitive dysfunction in diabetes mellitus （DM） by Jianpi Qinghua prescription （JPQH） based on type 2 diabetes （T2DM） model rats. MethodFifty healthy male Wistar rats of SPF grade were randomly divided into control group （n=10） and experimental group （n=40）. The rats in the control group were fed conventionally， while those in the experimental group were fed on a high-sugar， high-fat diet for six weeks and administered with streptozotocin （STZ） for the induction of the DM model. The model rats were randomly divided into model group， sitagliptin group （1.2 g·L-1）， pioglitazone group （0.8 g·L-1）， and JPQH group （1.3 g·mL-1）， with 10 rats in each group. After six weeks of drug intervention， the changes in body weight， blood glucose， and other related indexes of each group were recorded. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the peripheral blood and brain. The Morris water maze test was used to evaluate the cognitive function in rats. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of the hippocampal CA region. The amyloid β-protein 40 （Aβ40） level was detected by immunohistochemistry. The protein expression of t-tau and p-tau in hippocampal neurons of rats was detected by Western blot. ResultCompared with blank group， the body weight of model group was significantly decreased （P<0.05）， blood glucose level was significantly increased （P<0.01）， inflammatory cytokines TNF-α and IL-1β were increased （P<0.05）， learning and spatial ability were significantly decreased （P<0.01）， the arrangement of hippocampal cells was loose and disordered， and the intercellular space was significantly increased. The number of cells decreased significantly， and the expression of Aβ40 increased significantly. and increased t-tau and p-tau protein content in the hippocampus （P<0.01）. Compared with model group， the JPQH group showed reduced blood glucose （P<0.01）， decreased TNF-α and IL-1β levels in the peripheral blood and cerebrospinal fluid （P<0.05）， a downward trend of IL-6 without a statistical difference， improved learning and spatial memory ability （P<0.01）， densely arranged cells in the hippocampal CA1 area， increased cell number， reduced Aβ40 expression， and decreased p-tau protein expression （P<0.05）. ConclusionJPQH can prevent cognitive dysfunction in DM by reducing inflammatory factor levels， decreasing neurotoxicity caused by Aβ40 deposition， and inhibiting hyperphosphorylation of tau protein in DM rats.
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Antibacterial therapy is a global health issue. The antibiotic resistance is becoming an increasingly serious threat, which caused by misuse and overuse of antibacterial agents combined with the emergence of new resistance mechanism. The resulting infection treatment risk and incidence of the spread of disease, severe cases and deaths are increased in different degrees. With the extensive application of biomaterials and nanotechnology to biomedicine, extensive research has been conducted on antibacterial infection. With the specific physicochemical properties like optical, electric and magnetic and high penetration, inorganic nanomaterials can produce natural antibacterial effect. Nanomedicine can be designed to allow controlled drug release and targeting effect, thus demonstrated better antibacterial efficiency. In this review, the mechanism of antibacterial resistance is described, and the antibacterial infection research on inorganic nanomaterials, as well as nano-drug delivery system including liposomes, nanoparticles, dendrimers and biomimetic nanocarriers are summarized. Nanomaterials and nanotechnology offer promising strategies for the development of new agents that can improve efficacy on antibacterial infections and overcome antibiotic resistance potentially.
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AIM: To valuate the efficacy of 0.01% atropine for controlling myopia in children of different ages.METHOD: A randomized, double-blind, placebo control and single-center study was conducted. A total of 295 myopic children, aged 6～13 years, with myopia of -0.5D～-6.00D and astigmatism ≤2.0D, who admitted to our hospital from May 2019 to May 2020 were randomly assigned to experimental group(197 cases)and control group(98 cases)in a 2:1 ratio. Two groups were further divided into three subgroups according to age, 6～8 years old group(40/26 cases), 9～10 years group(84/34 cases), and 11～13 years group(73/38 cases). 0.01% atropine was administrated in the experimental group and placebo was administrated in the control group once before sleep. The changes of parameters were compared before and at 2wk, 3, 6, 9 and 12mo after treatment. Intraocular pressure, accommodation amplitude, best corrected distance and near visual acuity, pupil diameter and tear film were tested at 2wk. Cycloplegic refraction was assessed before treatment, and at 6 and 12mo after treatment.RESULTS: The spherical equivalent and axial length progression at 12mo after administration was -0.37±0.69D and 0.29±0.24mm in the experimental group, and -0.59±0.65D and 0.37±0.23mm in the control group(P=0.008, 0.006). In 6～8 years group, spherical equivalent and axial length progression between experimental and control group were not statistically significant(t=0.054, P=0.957; t=-0.623, P=0.536). In 9～10 years group, spherical equivalent and axial length progression between groups were statistically significant(t=2.056, P=0.042; t=-2.057 P=0.042). In 11～13 years group, spherical equivalent and axial length progression between groups were statistically significant(t=2.33, P=0.022; t=-2.424, P=0.017). The pupil was slightly dilated and the accommodation amplitude was decreased in experimental group, and the mean pupil diameter of the two groups was 3.94±0.79 and 3.16±0.48 mm respectively at 12mo after treatment(P<0.001). Other parameters and adverse event noted between groups were not statistically significant.CONCLUSIONS: 0.01% atropine is helpful to control the progression of myopia in children, which is well tolerated by adolescents. However, the effect of 0.01% atropine on the control of myopia for children aged 6～8 years is not enough. The findings suggest that increased concentration of atropine can be tried for 6～8 years old.
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ObjectiveTo summarize the echocardiographic features of sinus of Valsalva aneurysm （SVA）， analyze the causes of missed diagnosis， thus explore the diagnostic skills and improve the diagnostic accuracy for SVA. MethodsThe echocardiographic features and clinical data of 52 SVA patients who underwent surgery in the First Affiliated Hospital of Sun Yat-sen University from January 2014 to March 2022 were retrospectively reviewed. The patients were divided into 5 types according to modified Sakakibara classification system. ResultsThere were 32 male and 20 female patients with their age of 18~66 （36.1±11.6） years. Of the 52 aneurysms， 44 originated from the right coronary sinus （RCS）， 8 from noncoronary sinus （NCS） and none from left coronary sinus （LCS）. Among the 35 SVAs protruding into the right ventricle， including type I， type Ⅱ and type Ⅲv， 32 （91.4%） were associated with ventricular septal defect （VSD）. There were 2 （17.6%） associated with VSD among the 17 SVAs protruding into the right atrium or other sites of the heart， including type Ⅲa， type Ⅳ and type Ⅴ. SVA was frequently associated with aortic valve disease， 27 cases （51.9%） of which needed surgical valve replacement or valvoplasty. SVA was missed in 4 patients and VSD in 8， with the misdiagnosis rates of 7.7% and 23.5%， respectively. The most commonly missed VSD diagnosis was subarterial VSD with type I SVA. Of the 19 SVAs associated with infective endocarditis （IE）， 2 were missed， with the misdiagnosis rate of 10.5%. ConclusionThe ultrasound images of SVA are diverse and complex. SVA protruding into the right atrium is rarely associated with VSD， while SVA protruding into the right ventricle is frequently associated with VSD. SVA is also prone to be associated with aortic valve disease and IE， which makes the diagnosis more challenging. Therefore， during ultrasound examination， we must vigilantly and flexibly make use of the multiple scan slices so as to decrease the rate of missed diagnosis and improve the diagnostic accuracy for SVA.
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ObjectiveTo compare the outcomes in controlled ovarian stimulation （COH） and fresh embryo transfer between women with and those without a high basal luteinizing hormone （bLH） level in polycystic ovary syndrome （PCOS）. MethodsThe clinical data of PCOS patients at the Reproductive Medicine Center of the Sixth Hospital of Sun Yat-sen University from January 2015 to December 2021 were retrospectively analyzed. They were divided into the high group （LH≥10 U/L） and normal group （LH<10 U/L） according to the bLH levels. The results of COH and pregnancy outcomes after fresh transfer were compared， including gonadotropin （Gn） initiation dose， Gn duration， total Gn dose， number of oocytes obtained， two pronuclei （2PN） rate， available embryos rate， high-quality embryos rate， blastocyst formation rate， human chorionic gonadotrophin （HCG） positive rate， clinical pregnancy rate （CPR）， spontaneous abortion rate （SAR）， ongoing pregnancy rate （OPR） and live birth rate （LBR）. The differences in hormonal trends during COH were also analyzed. ResultsThere were no statistically significant differences in age， body mass index， anti-Mullerian hormone， and type of infertility between the two groups. Compared with the normal group， the Gn initiation dose and Gn duration were not statistically significant （P>0.05）， while the total Gn dose was significantly lower （P<0.001） in the high group. The number of oocytes retrieved， 2PN rate， available embryos rate， high-quality embryos rate， and blastocyst formation rate were comparable between the two groups （all P>0.05）. After fresh embryo transfer， they had similar pregnancy outcomes in the HCG positive rate， CPR， SAR， OPR and LBR （all P > 0.05）. ConclusionsIn patients with PCOS， high bLH levels do not affect COH or pregnancy outcomes in fresh transfer cycles. Further studies are needed to determine whether LH levels need to be lowered prior to COH and whether frozen-all strategy is required in patients with elevated bLH levels.
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Objective To investigate the changes of clinical indices in chronic hepatitis B (CHB) patients with concomitant minimal hepatic steatosis and related factors for minimal hepatic steatosis. Methods A total of 179 CHB patients who underwent liver biopsy in Department of Infectious Diseases, Affiliated Drum Tower Hospital of Nanjing University Medical School, from July 2018 to March 2022 were enrolled, and according to the degree of steatosis, they were divided into non-steatosis group with 98 patients and minimal hepatic steatosis group with 81 patients. Demographic information, clinical data, and liver histopathology data were collected, and related observation indices were compared between the two groups. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was performed, and a Logistic regression analysis was used to investigate the risk factors for minimal hepatic steatosis. Results Compared with the non-steatosis group, the minimal hepatic steatosis group had a significantly higher proportion of male patients (69.1% vs 52.0%, χ 2 =5.390, P < 0.05) and a significantly higher proportion of patients with significant liver fibrosis (43.2% vs 25.5%, χ 2 =6.234, P < 0.05). Compared with the non-steatosis group, the minimal hepatic steatosis group had significantly higher levels of body mass index (BMI) (23.61±2.95 kg/m 2 vs 22.13±2.67 kg/m 2 , t =-4.150, P < 0.05), uric acid (UA) [333.0(291.0-375.5) μmol/L vs 287.5(244.8-345.3) μmol/L, Z =-3.620, P < 0.05], triglyceride [0.92 (0.66-1.14) μmol/L vs 0.77 (0.62-1.02) μmol/L, Z =-2.224, P < 0.05], and controlled attenuation parameter (CAP) [234 (214-258) dB/m vs 218 (201-237) dB/m, Z =-2.867, P < 0.05]. In the group with normal body weight, the patients with minimal hepatic steatosis had significantly higher levels of UA (333.0±63.9 μmol/L vs 291.0±72.8 μmol/L, t =-2.395, P < 0.05) a nd HBV DNA [4.44 (3.51-6.79) log 10 IU/mL vs 3.42 (3.00-5.03) log 10 IU/mL, Z =-2.474, P < 0.05]. BMI (odds ratio [ OR ]=1.223, 95% confidence interval [ CI ] : 1.086-1.378, P =0.001) and UA ( OR =1.006, 95% CI : 1.002-1.010, P =0.008) were risk factors for minimal hepatic steatosis in CHB patients, and UA ( OR =1.007, 95% CI : 1.001-1.013, P =0.022) was a risk factors for minimal hepatic steatosis in CHB patients with normal body weight. Conclusion Compared with the non-steatosis CHB patients, the CHB patients with minimal hepatic steatosis have a significantly higher proportion of patients with significant liver fibrosis and a significantly higher level of CAP. BMI and UA are independent risk factors for minimal hepatic steatosis in CHB patients, and for the CHB patients with normal body weight, elevated UA is closely associated with the onset of minimal hepatic steatosis.
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OBJECTIVE To systematically evaluate the efficacy and safety of glucokinase activators in the treatment of type 2 diabetes mellitus. METHODS PubMed， Cochrane Library， Web of Science， Embase and CNKI databases were searched from the inception to March 2022. Randomized controlled trials about glucokinase activators versus placebo （or other oral hypoglycemic agents） in the treatment of type 2 diabetes were included， data were extracted and meta-analysis was analyzed using RevMan 5.4 software. RESULTS A total of 9 studies with 215 0 patients were included. In terms of hypoglycemic effect， compared with control group， glucokinase activators significantly reduced glycosylated hemoglobin （HbA1c） [MD＝－0.40， 95%CI（－0.53， －0.26）， P＜0.000 01]， fasting blood glucose[MD＝－0.53， 95%CI（－0.85， －0.20）， P＝0.001] and 2 h postprandial blood glucose [MD＝－2.28， 95%CI（－2.68， －1.88）， P＜0.000 01] in diabetic patients. In terms of safety， the incidence of hypoglycemia caused by glucokinase activators was higher than control group on the whole [RR＝1.55， 95%CI（1.20，2.01）， P＝ 0.000 8]. According to the subgroup analysis of organs activated by glucokinase activator， the incidence of hypoglycemia in the pancreas-liver dual activator group [RR＝1.44， 95%CI（1.11，1.89）， P＝0.007] and liver-selective activator group [RR＝2.26， 95%CI（1.02，5.03）， P＝0.05] was higher than that in the control group， the difference was statistically significant. CONCLUSIONS Glucokinase activators can effectively reduce HbA1c， fasting blood glucose and 2 h postprandial blood glucose in patients with type 2 diabetes， but the risk of hypoglycemia remains to be addressed.
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Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease affecting multiple systems and organs, which leads to a variety of comorbidity, including an important impact on the body′s endocrine system comorbidities. COPD comorbidity will affect the severity and prognosis of the disease, and so does thyroid dysfunction. However, the specific mechanism is not clear, and previous studies suggest that hypoxia, inflammatory factors may be involved. However, the treatment of patients with COPD associated with thyroid dysfunction is still controversial. Further understanding of the relationship between this comorbidity and COPD is of great clinical significance. This article reviews the relevant studies, hoping to provide useful ideas for the exploration of the mechanism and treatment of COPD with thyroid dysfunction.
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Objective:To investigate the clinical efficacy of second-line therapy with dasatinib in the treatment of chronic myeloid leukemia.Methods:Sixty patients with chronic phase chronic myeloid leukemia who received treatment in Hongqi Hospital of Mudanjiang Medical University between January 2015 and January 2021 were included in this study. They were randomly divided into control and observation groups, with 30 patients in each group. The control group was treated with conventional chemotherapy, and the observation group was treated with conventional chemotherapy combined with oral dasatinib. All patients were treated for 6 months. Clinical efficacy, immune function indexes, quality of life score, and incidence of adverse reactions (abnormal liver function, rash, fatigue, peripheral edema, nausea and vomiting, alopecia) were compared between the two groups.Results:Objective response rate (ORR) in the observation group was significantly higher than that in the control group [83.33% (25/30) vs. 53.33% (16/30), χ2 = 6.23, P < 0.05). Before treatment, there were no significant difference in immune function indicators between the two groups ( t = 0.03, 0.20, 0.44, all P > 0.05). After treatment, CD 4/CD 8, CD 3+ and natural killer cells in the observation group were (1.03 ± 0.32), (43.77 ± 6.62)%, (31.12 ± 3.38)%, respectively, which were significantly higher than (0.74 ± 0.28), (35.79 ± 6.27)%, (28.22 ± 2.84)% in the control group ( t = 3.69, 4.78, 3.60, all P < 0.05). The scores of social functioning, material well-being life, mental health, somatic health in the observation group were (85.48 ± 6.25) points, (80.12 ± 6.34) points, (79.94 ± 6.48) points, and (77.92 ± 5.81) points, respectively, which were significantly higher than (72.79 ± 5.89) points, (63.47 ± 5.82) points, (68.87 ± 6.08) points, (63.14 ± 6.12) points in the control group ( t = 7.91, 10.59, 6.82, 9.59, all P < 0.05). The incidence of adverse reactions in the observation group was significantly lower than that in the control group [16.67% (5/30) vs. 40.00% (12/30), χ2 = 4.02, P < 0.05). Conclusion:Second-line therapy with dasatinib for chronic phase chronic myeloid leukemia is effective and safe. It can effectively improve the efficacy and safety of chemotherapy and can also improve immunological function and quality of life.
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Objective:To learn about the arsenic status of drinking water in Urumqi City and evaluate its health risk, so as to provide scientific basis for the construction of water improvement projects in Urumqi City.Methods:From 2018 to 2020, 687 water samples were collected at monitoring sites in 7 districts and 1 county of Urumqi City for three consecutive years, and arsenic in drinking water was detected according to "Standard Examination Methods for Drinking Water - Nonmetal Parameters" (GB/T 5750.5-2006), and the arsenic in drinking water was evaluated according to "Standards for Drinking Water" (GB/T 5749-2006). The health risk of arsenic in drinking water in Urumqi City was evaluated by using the health risk assessment model recommended by United States Environmental Protection Agency (USEPA).Results:All of 687 water samples were centralized water supply, the arsenic compliance rates in dry season ( n = 342) and wet season ( n = 345), surface water ( n = 414) and underground water ( n = 273) were 100.0%. In dry season, the carcinogenic risk of arsenic via drinking water was 8.24 × 10 -6/a. In wet season, the carcinogenic risk of arsenic via drinking water was 3.30 × 10 -6/a. Conclusions:Remarkable achievements have been made in the construction of water improvement projects in Urumqi City, and the drinking water arsenic condition is good, the health risk of arsenic via drinking water is small. In the future, we should continue to strengthen the monitoring of drinking water quality, promote the construction of water improvement projects, further improve the drinking water sanitation, and put forward targeted prevention and control measures to ensure drinking water safety.
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Objective:To explore the role of scenario simulation exercise combined with formative assessment in the teaching of operating room interns.Methods:A total of 86 interns received by the operating room from April 2019 to March 2020 were selected and divided into control group and study group according to the order of internship, with 43 interns in each group. Traditional clinical teaching was used in the control group, and the clinical teaching of scenario simulation exercise combined with formative assessment was used in the study group. The assessment results of theoretical knowledge and operational skills, the changes of clinical comprehensive ability before and after practice and the recognition of teaching were compared between the two groups. SPSS 25.0 was used for t test and chi-square test. Results:After practice, the scores of theoretical knowledge and operational skills in the study group were significantly higher than those in the control group ( P < 0.05). There was no statistical difference in the scores and total scores of professional knowledge application ability, health education ability, basic skill operation, professional skill operation, evaluation and diagnosis ability, information processing ability, communication and communication ability, adaptability, teamwork ability and professional attitude of the two groups before the internship. After the internship, the above scores and total scores were higher than those before the internship, with statistically significant differences ( P<0.05), and the scores and total scores of the study group were higher than those of the control group ( P<0.05). The total recognition rate of teaching in study group (93.02%, 40/43) was higher than that in the control group (76.74%, 36/43), with statistically significant differences ( P<0.05). Conclusion:The teaching method of scenario simulation exercise combined with formative assessment applied to the practice of physicians in the operating room can significantly improve the mastery level of theoretical knowledge and operational skills, clinical comprehensive ability and recognition of teaching.
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Objective:To summarize the clinical characteristics, causes of misdiagnosis and preventive measures of infectious mononucleosis (IM) in children, and to improve the ability of clinicians in early diagnosis of IM in children.Methods:The clinical data of 468 children with IM in Xi′an Children′s Hospital from January 2018 to December 2021 were retrospectively analyzed, including general situation, disease onset, diagnosis and misdiagnosis.Results:Among the 468 children, 33 cases were clinically diagnosed and 435 cases were a definitely diagnosed; 281 males (60.04%) and 187 females (39.96%); the incidence rate was highest in preschool children (43.80%, 205/468) and in autumn (33.12%, 155/468). The first symptoms were fever (52.99%, 248/468), eyelid edema (15.38%,72/468) and neck mass (14.96%, 70/468). The fever rate was 90.38% (423/468), and the median time of first fever appearance was on the first (first, second) day of disease course, and the median duration of fever was 6 (4, 8) d. The median time of first visit was on the third (first, fifth) day of disease course, and the time of diagnosis was on the seventh (fifth, ninth) day of disease course. Blood routine examination showed that the proportion of white blood cell count increased was 51.92% (243/468), the proportion of lymphocytes increased was 61.75% (289/468), and the proportion of abnormal lymphocytes increased (≥10%) in peripheral blood was 58.97% (276/468). The lymphocyte subsets of 364 children were detected, the rate of helper T lymphocytes (Th cells) decreased was 80.22% (292/364), the rate of suppressor T lymphocytes (Ts cells) increased was 99.45% (362/364), the value and decreased rate of Th cells/Ts cells were 0.24 (0.16, 0.40) and 100.00% (364/364), rate of B lymphocytes decreased was 93.96% (342/364), rates of natural killer cells decreased and increased were 35.16% (128/364) and 0.55% (2/364). The misdiagnosis rate was 55.13% (258/468), and the misdiagnosis time was on the fifth (fourth, seventh) day of disease course. Among the 258 misdiagnosed children, 105 cases (40.70%) were misdiagnosed as upper respiratory tract infection, 65 cases (25.19%) as acute suppurative tonsillitis, 27 cases (10.47%) as acute cervical lymphadenitis or neck mass.Conclusions:Due to the complex and diverse clinical manifestations of IM in children, it is easy to be misdiagnosed in the early stage of the disease. So, it is necessary for clinicians to master the clinical characteristics of IM in children, constantly improve the level of diagnosis and treatment, and reduce the misdiagnosis rate.
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Objective:To analyze the clinical phenotypes and pathogenic gene of a Han Chinese family with enhanced S-cone syndrome (ESCS).Methods:The method of pedigree investigation was adopted.A suspected ESCS Han Chinese family including 8 members of 3 generations was recruited in Henan Eye Hospital from June to September 2021.There was one patient in the family.A thorough ophthalmic examination of the proband was carried out to evaluate the phenotypes, including visual acuity, degree of strabismus, anterior segment and fundus, autofluorescence imaging, fluorescein fundus angiography, full-field electroretinogram (ERG), multifocal ERG, optical coherence tomography.DNA was extracted from peripheral blood samples from the proband and family members.The pathogenic gene and variation were screened by whole exome sequencing (WES).The variation and co-segregation were verified by Sanger sequencing.The deleteriousness of the variation was analyzed by SIFT, Polyphen2 and MutationTaster.The pathogenicity of the variation was evaluated in accordance with the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines.The analysis of amino acid sequence conservation was performed by SIFT.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2017[6]).Written informed consent was obtained from each subject.Results:This pedigree was consistent with autosomal recessive inheritance.The proband had clinical features such as night blindness, hyperopia, accommodative esotropia, peripheral retinal pigmentation, retinoschisis, and photopic ERG responses dominated by large-amplitude waves.Variations including a compound heterozygous variation, c.671C>T: p.S224L on exon 5 and c. 955G>A: p.E319K on exon 6 of NR2E3 were identified by WES.The variations were confirmed to be consistent with co-segregation.The both loci were missense variations, the variation frequency of which was 0 in the East Asian population via the gnomAD database.The variations were predicted to be deleterious by SIFT, Polyphen2 and MutationTaster.The c.671C>T variation was recorded with unknown significance in ClinVar database, and the c.955G>A variation was an unreported new locus.According to the ACMG Standards and Guidelines, the both variations were labeled as with uncertain clinical significance, and the corresponding amino acid sequences were highly conservative across multiple species. Conclusions:This family has the clinical characteristics of ESCS and meets the genetic diagnosis criteria.Two novel variations in NR2E3 gene, c.671C>T: p.S224L and 955G>A: p.E319K, are found.
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AIM:To discuss the efficacy and safety of orthokeratology with reducing back optic zone diameter(5mm-BOZD)compared with conventional back optic zone diameter(6mm-BOZD)in the treatment of adolescent myopia.METHODS: A prospective randomized controlled trial was performed. There were 100 cases with 100 eyes of adolescent myopia(all right eye data were taken)selected from April 2016 to January 2019, the spherical degree was -1.00--5.00D. Then they were randomly divided into the two groups. The experimental group wore 5mm-BOZD orthokeratology, and the control group wore 6mm-BOZD orthokeratology. Their axis length(AL), spherical equivalent(SE), relative peripheral refraction(RPR), best corrected visual acuity(BCVA), uncorrected near visual acuity(NVA), Efron grading was applied to record the anterior segment of the eyes, corneal hysteresis(CH), corneal resistance factor(CRF), corneal-compensated intraocular pressure(IOPcc), average noninvasive Keratograph tear breakup time(NIKBUTav)and higher order aberration(RMSh) were compared between the two groups during the 1a treatment period.RESULTS: After 1a of treatment, the AL in experimental group increased 0.05±0.05mm,while it increased 0.15±0.05mm(t=-8.949, P<0.001)in control group. The SE in experimental group increased -0.18±0.27D,while it increased-0.42±0.35D(t=3.609, P=0.001)in control group. There were statistical differences in RPR changes at N30°, N20° and T30°sites between the two groups(P<0.05). There were no statistical differences in BCVA,NVA,Efron grade,CH,CRF,IOPcc,NIKBUTav and RMSh between the two groups(P>0.05).CONCLUSION:Reducing back optic zone diameter orthokeratology can correct adolescent myopia safely and more effectively during the observation period.
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Objective:To investigate the methylation status of SDC2, PPP2R5C and ADHFE1 genes in stool and their values in the screening of colorectal cancer and precancerous lesions.Methods:From August 2020 to March 2021, 64 patients with colorectal cancer, 72 patients with adenoma, 33 patients with hyperplastic polyps and 59 healthy people were recruited from Qingdao Central Hospital Affiliated to Qingdao University, and the morning stool samples were collected from the research subjects. The genomic DNA was extracted and modified with sulfite. The methylation status of SDC2, PPP2R5C and ADHFE1 genes were detected by methylation specific polymerase chain reaction (MSP), and the fecal occult blood test (FOBT) was performed. Taking the pathological results as the gold standard, receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to compare the effect of combined detection of methylation of three genes and FOBT in predicting colorectal cancer and precancerous lesions. R-Studio software was used to construct a nomogram for the prediction of colorectal cancer with combined detection of gene methylation in stool and other clinical features, and the calibration and validation were performed.Results:The positive rates of combined detection of methylation of SDC2, PPP2R5C and ADHFE1 genes in stool were higher than those of FOBT in colorectal cancer+adenoma [74.3% (101/136) vs. 47.1% (64/136), χ2 = 23.20, P = 0.001], colorectal cancer [90.6% (58/64) vs. 70.3% (45/64), χ2 = 8.91, P = 0.003] and adenoma [59.7% (43/72) vs. 26.4% (19/72), χ2 = 14.43, P = 0.002]. There was no significant difference in the positive rates in hyperplastic polyps [21.2% (7/33) vs. 6.1% (2/33), χ2 = 0.12, P = 0.125] and healthy controls [10.2% (6/59) vs. 8.5% (5/59), χ2 = 4.01, P = 1.000]. The combined detection of gene methylation was better than FOBT in the prediction of colorectal cancer + adenoma [AUC: 0.85 (95% CI 0.80-0.91) vs. 0.71 (95% CI 0.64-0.78), P < 0.05], especially in the prediction of adenoma [AUC: 0.82 (95% CI 0.74-0.89) vs 0.64 (95% CI 0.57-0.69), P < 0.001]. The sensitivity and specificity of ADHFE1 gene methylation status in predicting colorectal cancer were high (90.6% and 96.6%). In colorectal cancer patients over 50 years old, the positive rate of combined detection of gene methylation was higher than that of FOBT [90.2% (55/61) vs. 68.9% (42/61), P < 0.05]. The nomogram calibration curve for predicting colorectal cancer constructed based on the combined detection of gene methylation and each clinical feature showed a high degree of concordance between the predicted and observed diagnostic performance of colorectal cancer. Conclusions:The methylation levels of SDC2, PPP2R5C AND ADHFE1 genes in stool are increased in patients with colorectal cancer or adenoma. The combined detection of gene methylation is expected to be a non-invasive method for the screening of colorectal cancer and precancerous lesions.
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As one of the diseases with high incidence in China， cancer seriously endangers human health. The scientific research and clinical practice of traditional Chinese medicine （TCM） in the prevention and treatment of tumors during the Sixth Five-Year Plan period and the 13th Five-Year Plan period show that TCM has certain advantages in preventing and treating postoperative metastasis and recurrence， prolonging survival period， alleviating adverse reactions， and improving the quality of life of patients with advanced tumors. However， innovation of the TCM theoretical thinking and realization of the TCM full-cycle management are needed urgently， which limits the improvement of clinical efficacy. Malignant tumor is a truly representative of major difficult diseases. The simple mode of syndrome differentiation and treatment cannot meet the clinical needs， and thus the triple mode of disease， syndrome and symptom differentiation and treatment emerged， and has received widespread attention. However， since malignant tumors have their own characteristics of occurrence， development and evolvement， it is urgent to establish a new system of TCM differentiation and treatment for special diseases to adapt to the law of modern disease development. Therefore， on the basis of the triple mode， this paper innovatively proposed a new system of cancer prevention and treatment based on five views on differentiation and treatment in TCM， forming a new paradigm of whole-cycle， whole-chain and all-directional integrated Chinese and western medicine prevention and treatment of tumors. Specifically， time-space view： On the basis of the holistic concept and combined with the complex characteristics of different pathological types， lesion location， disease course and treatment stages of malignant tumors， the dynamic and systematic participation of TCM in the whole process of tumor treatment was brought into play from the time and space dimensions. Core view： The core pathogenesis was summarized based on the combination of disease and syndrome， and its key role in guiding differentiation and treatment of malignant tumors was emphasized. Additionally， the pathogenesis characteristics and evolvement rules of various cancer types in different stages were paid attention. Symptom view： The symptoms were ameliorated and the quality of life was improved. The current obvious contradictions of patients were solved to enhance the humanistic nature of treatment. Precision view： In combination of modern medical concepts， TCM constitutions and laboratory indicators， TCM advantages were enriched and emphasized for precise clinical positioning. Disease-before-onset view： As prevention is more important than treatment， precaution was focused on in each stage of tumors. The five views had different emphases and were interrelated， covering new understandings of the existing TCM prevention and treatment system of malignant tumors. In addition， new ideas and concepts have been introduced on the basis of the original TCM theory， which provided new strategies for the comprehensive prevention and treatment of tumors.
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ObjectiveTo observe the protective effect of Sanhuatang and its modifications on the brain tissue of rats exposed to cerebral ischemia-reperfusion injury （CIRI） and explore its action mechanism and compatibility characteristics. MethodOne hundred and forty SD male rats of clean grade were randomly divided into the control group， sham-operation group， and operation group. The Longa suture method was employed to establish the CIRI model. The successfully modeled CIRI rats were further divided into five groups， namely the model group， nimodipine group， Sanhuatang without Notopterygii Rhizoma et Radix group， Notopterygii Rhizoma et Radix group， and Sanhuatang group， and treated with the corresponding medicines by gavage for five days. The cerebral infarct size in each group was examined by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and the pathological changes in the brain tissue were observed by hematoxylin-eosin （HE） staining and electron microscopy. The mRNA and protein expression levels of Claudin-5， Occludin， and zonula occludens-1 （ZO-1） in brain tissues were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the control group， the model group exhibited markedly increased infarct size， obvious changes in brain morphology and ultrastructure， and down-regulated mRNA and protein expression of Claudin-5， Occludin， and ZO-1 （P<0.01）. Compared with the model group， both nimodipine and Sanhuatang significantly decreased the infarct size （P<0.01） and relived the pathological changes. The infarct sizes in the Sanhuatang without Notopterygii Rhizoma et Radix group and Notopterygii Rhizoma et Radix group were reduced without exhibiting a statistically significant difference. The mRNA and protein expression levels of Claudin-5， Occludin， and ZO-1 in the nimodipine group， Sanhuatang group， and Notopterygii Rhizoma et Radix group were up-regulated significantly in comparison with those in the model group （P<0.01， P<0.01）. The mRNA and protein expression levels of Claudin-5 and ZO-1 were higher in the Notopterygii Rhizoma et Radix group than in the Sanhuatang without Notopterygii Rhizoma et Radix group （P<0.01， P<0.01）. ConclusionSanhuatang exerts the protective effect against CIRI in rats possibly by regulating the expression of Claudin-5， Occludin， and ZO-1 and improving the blood-brain barrier function. Notopterygii Rhizoma et Radix in Sanhuatang may play an important role in the protection of rats from CIRI.
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ObjectiveTo predict the therapeutic targets and related signaling pathways of orcinol glucoside （OG） in the treatment of osteoporosis by network pharmacology， and further clarify its mechanisms based on molecular docking and in vitro cell model. MethodThe pharmacological targets of OG were obtained from Similarity ensemble approach （SEA） and SwissTargetPrediction， and the targets related to osteoporosis from DisGeNET and GeneCards. The cross-analysis was conducted to screen the common targets between OG and osteoporosis. STRING was used to construct the protein-protein interaction （PPI） network， followed by topology analysis using CytoNCA plug-in of Cytoscape 3.7.2 to screen out the core targets. The obtained common targets were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） analysis by g：Profiler. AutoDock Vina was utilized for molecular docking， and the in vitro cell experiments were then carried out for verifying the mechanism of OG in treating osteoporosis. ResultA total of 73 targets related to OG and osteoporosis were harvested，among which 14 were proved to be key targets by topological analysis. GO and KEGG functional enrichment analysis yielded 259 cell biological processes， mainly involving organonitrogen compound metabolic process， cell population proliferation， protein metabolic process， regulation of response to stress， and response to chemicals. Its mechanism of action might be related to advanced glycation end-product （AGE）-AGE receptor （RAGE） signaling pathway， interleukin-17 （IL-17） signaling pathway， and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. Molecular docking indicated that the binding energies of OG to Cyclin D1 （CCND1） and cyclin-dependent kinase 4 （CDK4） were the lowest and similar. The results of flow cytometry showed that compared with the normal group， OG group exhibited decreased proportion of cells in G0/G1 phase （P<0.01） and decreased proportion of cells in S phase （P<0.01）. As demonstrated by Western blot， compared with the normal group， OG up-regulated the protein expression levels of Cyclin D1 and CDK4 （P<0.05， P<0.01）. ConclusionOG alleviates osteoporosis via multiple targets and multiple pathways. It may exert the therapeutic effects by increasing Cyclin D1 and CDK4 protein expression to change cell cycle and promote cell proliferation.
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Obstructive sleep apnea hypopnea syndrome(OSAHS)is a group of diseases which occurred in the upper respiratory tract with transient, recurrent, partial or complete obstruction during night sleep. It can affect the regulation of hemodynamics, endocrine systems and autonomic nerve, and then result in the reduction of body oxygen saturation, chronic hypoxia and hypercapnia. Beside being an independent risk factor for cardiovascular and cerebrovascular diseases, many studies have shown that it is also associated with ocular surface diseases in OSAHS, such as floppy eyelid syndrome, dry eye, keratoconus, etc., but there is still a lack of perfect systematic analysis. This paper reviews the relationship between OSAHS and relevant ocular surface diseases including pathogenesis,clinical manifestations and treatment progress, in order to reduce the ophthalmic complications of OSAHS patients in clinical diagnosis and treatment,and better improve the quality of life of patients.