CRISPR/Cas9-mediated Knockout of KIFC1 Inhibits Proliferation and Induces Apoptosis of Cervical Cancer Cells / 肿瘤防治研究

Objective To investigate the functions of the KIFC1 gene in tumor cells and its effect on the proliferation of cervical cancer cells. Methods We designed sgRNAs targeting the KIFC1 gene and constructed a recombinant plasmid based on the pSpCas9 (BB)-2A-GFP vector, which was co-transfected into HeLa cells. We screened monoclonal knockout cell lines through flow cytometry sorting, limited dilution inoculation of cells, and sequencing. RT-qPCR, Western blot, and immunofluorescence were used to detect the transcription and protein expression levels of KIFC1 in knockout cells. Cell phenotypes such as nucleus and microtubule cytoskeleton were observed using phase-contrast microscopy and fluorescence confocal microscopy. Cell proliferation, cell cycle, and apoptosis were analyzed by growth curve plotting, EdU labeling, and acridine orange staining. Results The deletion of the KIFC1 gene resulted in the abnormal phenotypes of HeLa cells, with increased numbers of multinuclei, micronucleus, and disordered microtubules. The cell cycle was disrupted, accompanied with a significant increase in the ratio of late apoptotic cells and a decrease in cell proliferation (all P < 0.05). Conclusion KIFC1 gene deletion affects the assembly of microtubules and cell division in HeLa cells, leading to abnormal nuclear morphology, chromatin elimination, cell cycle arrest, and increased cell apoptosis.

Analysis of multimodal ultrasound characteristics of statin-related myopathy in elderly patients with hyperlipidemia / 中华老年医学杂志

Objective:To investigate the characteristics of multimodal ultrasound imaging in elderly hyperlipidemia patients with statin-related myopathy and to provide a reference of new method for non-invasive quantitative evaluation on statin myopathy.Methods:We collected 20 elderly hyperlipidemia patients with statin-related myopathy(the statin-related myopathy group), 20 elderly hyperlipidemia patients without statin-related myopathy after taking statins during the same period(the non-statin-related myopathy group), and 20 healthy volunteers who matched the age and sex of the above two groups during the same period(the healthy control group)in our hospital.Two-dimensional ultrasound, shear wave elastography and superb microvascular imaging were used to obtain thickness, echo, pinnation angle and shear wave velocity(SWV)values as well as vascular index(VI)values of the medial gastrocnemius during relaxation, dorsiflexion, and plantar flexion for each group, which were then analyzed.Results:There were no significant differences among the three groups in general conditions such as age, height, weight, and body mass index(all P>0.05). The mean thickness of the medial gastrocnemius in the statin-related myopathy group was about(1.04 ± 0.20)cm, which was less than(1.34 ± 0.16)cm in the non-statin-related myopathy group and(1.35 ± 0.15)cm in the healthy control group( F=22.03, P<0.001). The pinnation angle in the statin-related myopathy group was about(12.50 ± 1.10), which was less than(18.55 ± 1.28)in the non-statin-related myopathy group and(18.60 ± 1.35)in the healthy control group( F=158.03, P<0.001). Compared with the non-statin-related myopathy group and the healthy control group, SWV during resting, dorsiflexion and plantar flexion in the statin-related myopathy group decreased( F=61.71, 111.96 and 8.69, respectively, P<0.01). The average value of VI in the statin-related myopathy group was about(0.43 ± 0.12)%, which was less than that in the non-statin-related myopathy group(0.75 ± 0.20)% and in the healthy control group(0.93 ± 0.17)%( F=48.93, P<0.001). However, there was no significant difference in values from the parameters between the non-statin-related myopathy group and the healthy control group(all P>0.05). Conclusions:Multimodal ultrasound imaging of statin-related myopathy in elderly hyperlipidemia patients shows distinct characteristics and can be used to evaluate muscle damage of statin-related myopathy.

Experts consensus on the management of delirium in critically ill patients / 中华内科杂志

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Application value of oral contrast-enhanced ultrasonography in the diagnosis of gastric tumors in the elderly / 中华老年医学杂志

Objective To investigate the diagnostic value of ultrasonography.in elderly patients with gastric tumors.Methods A total of 42 elderly patients with gastric tumors confirmed by surgery pathology underwent oral contrast-enhanced ultrasonography and electronic gastroscopy.The diagnostic effect of oral contrast-enhanced ultrasonography and electronic gastroscopy were compared based on the gold standard of surgical pathology.Results Of the 42 elderly patients with gastric tumors,40 patients were diagnosed by oral contrast-enhanced ultrasonography and the surgical pathology(40/42,95.2％),with Kappa value of 0.812.And 38 cases were diagnosed by electronic gastroscopy and the surgical pathology(38/42,90.5 ％),with Kappa value of 0.718 (P ＜ 0.05).Based on gold standard of surgical pathology results,the accuracies of T1,T2,T3 and T4 stage by oral contrast-enhanced ultrasonography were 95.0％ (38/40),95.0％ (38/40),100.0％ (40/40) and 100.0％(40/40),respectively.The sensitivity and specificity of T3 and T4 stage for oral contrastenhanced ultrasonography reached to 100.0 ％.The diagnostic accuracies of N0,N1-N3,M0 and M1 by oral contrast-enhanced ultrasonography were 95.0 ％ (38/40),95.0 ％ (38/40),100.0 ％ (40/40) and 100.0％(40/40).Conclusions Oral contrast-enhanced ultrasonography is a simple,painless and non-invasive method for the diagnosis of gastric tumors in the elderly.And its qualitative coincidence rate of the tumors diagnosis is similar to that of gastroscopy.So it can be used as the first choice for the examination of gastric tumors in the elderly.Oral contrast-enhanced ultrasonography has a high diagnostic accuracy on TNM staging of gastric tumor.When combined with electronic gastroscopy,it may provide a more reliable basis for the choice of evaluation of treatment and prognosis in elderly patients with gastric tumor.

Application value of oral contrast-enhanced ultrasonography in the diagnosis of gastric tumors in the elderly / 中华老年医学杂志

Objective@#To investigate the diagnostic value of ultrasonography.in elderly patients with gastric tumors.@*Methods@#A total of 42 elderly patients with gastric tumors confirmed by surgery pathology underwent oral contrast-enhanced ultrasonography and electronic gastroscopy.The diagnostic effect of oral contrast-enhanced ultrasonography and electronic gastroscopy were compared based on the gold standard of surgical pathology.@*Results@#Of the 42 elderly patients with gastric tumors, 40 patients were diagnosed by oral contrast-enhanced ultrasonography and the surgical pathology(40/42, 95.2%), with Kappa value of 0.812.And 38 cases were diagnosed by electronic gastroscopy and the surgical pathology(38/42, 90.5%), with Kappa value of 0.718(P<0.05). Based on gold standard of surgical pathology results, the accuracies of T1, T2, T3 and T4 stage by oral contrast-enhanced ultrasonography were 95.0%(38/40), 95.0%(38/40), 100.0%(40/40)and 100.0%(40/40), respectively.The sensitivity and specificity of T3 and T4 stage for oral contrast-enhanced ultrasonography reached to 100.0%.The diagnostic accuracies of N0, N1-N3, M0 and M1 by oral contrast-enhanced ultrasonography were 95.0%(38/40), 95.0%(38/40), 100.0%(40/40)and 100.0%(40/40).@*Conclusions@#Oral contrast-enhanced ultrasonography is a simple, painless and non-invasive method for the diagnosis of gastric tumors in the elderly.And its qualitative coincidence rate of the tumors diagnosis is similar to that of gastroscopy.So it can be used as the first choice for the examination of gastric tumors in the elderly.Oral contrast-enhanced ultrasonography has a high diagnostic accuracy on TNM staging of gastric tumor.When combined with electronic gastroscopy, it may provide a more reliable basis for the choice of evaluation of treatment and prognosis in elderly patients with gastric tumor.

A literature review for 153 cases of thyrotropin-secreting pituitary adenomas in China / 中华内分泌代谢杂志

Objective To explore the clinical characteristics of patients with thyrotropin-secreting pituitary adenomas ( TSHomas) in China. Methods All the articles related to TSHomas were retrieved from the Chinese journal databases up to July 2017. All reported cases were assessed. Results TSHomas have been diagnosed in all ages (range:12-81 years old, average 41.9 ± 13.8 years old) with no gender difference (male : female=84: 69). The rate of misdiagnosis fell from 84.6％(11/13) to 50.6％(39/77) in the last 10 years. In 92 cases (60.1％), the level of TSH was elevated [median 1.57×ULN (upper limits of normal)]. The most common elevated hormones associated with TSHomas were growth hormone ( GH) and prolactin ( PRL;11.1％and 9.7％, respectively) . 37 cases underwent octreotide suppression test, of which the inhibitory rates ranged from 26. 2％ to 94. 9％ ( median 71.79％). The detection rate of micro-adenoma was 7.7％(1/13)before year 2000, 11.4％(4/35)from 2000 to 2006, and 26.7％(28/105) after 2006. Although TSHomas usually invade surrounding tissues, they hardly cause pituitary apoplexy. Surgery orγ-knife was performed in 132 cases ( 86. 3％) . Immunohistochemistry of tumors showed that 87 (52.9％) of 46 were pure TSH adenomas and 32 (36.8％) cases were mixed ones, while GH and PRL were most common (75.0％and 56.3％respectively) in the mixed adenomas. Negative immunohistochemistry for TSH was found in 9 cases (10.3％). In the follow-up, the restoring rates of thyroid hormone and TSH level were 77.0％(87/113) and 80.0％( 36/45) respectively. Conclusion TSHoma is diagnosed at an earlier age in China than that reported in Europe and America, while at similar age compared with Japan. Macro-adenomas were more common in spite of the increasing detection rate of micro-adenomas. Macro-adenomas are often invasive but less likely to induce pituitary apoplexy. Immunostaining for TSH could be negative. The most common positive immunostaining in mixed adenoma is GH and/or PRL. However, a positive immunostaining for one pituitary hormone does not necessarily correlates with its hypersecretion of that hormone.

A comparative study of the clinical features of thyrotropin-secreting pituitary adenomas / 解放军医学杂志

Objective To comparatively analyze the clinical characteristics of thyrotropin-secreting pituitary adenomas (TSH-omas).Methods The clinical features, laboratory variables, imaging and pathological Results were retrospectively compared and analyzed of 26 cases with TSH-omas admitted in Chinese PLA General Hospital from Feb. 2006 to Oct. 2016 and 20 cases with TSH-omas admitted in Shanghai Huashan Hospital from Apr. 2006 to Apr. 2013.Results The female ratio was slightly higher in patients of Chinese PLA General Hospital than in Huashan Hospital [(57.7%(15/26)vs. 45.0%(9/20)], while the mean age was similar [39.5±14.1(18-67 years)vs. 40.0±14.5(17-74 years)]. The most common chief complaint was thyrotoxicosis [73.1%(19/26)vs. 55.0%(11/20)], and mild-to-moderate goiter was the most common symptom. The mean serum TSH levels in Chinese PLA General Hospital and in Huashan Hospital were 5.06(2.97-6.27)mU/L and 6.16(3.76-10.91)mU/L respectively, and patients with normal serum TSH levels were more common in Chinese PLA General Hospital than in Huashan Hospital [57.7%(15/26)vs. 40.0%(8/20)]. Microadenoma was more common in Chinese PLA General Hospital than in Huashan Hospital [34.62%(9/26)vs. 20.0%(4/20)], while macroadenoma was more common in Huashan Hospital than in Chinese PLA General Hospital [20.0%(4/20)vs. 7.7%(2/26)]. Microadenoma was more common in female patients of the both groups [66.7%(6/9)vs. 75.0%(3/4)], while macroadenoma was all found in male patients. Tumor invasion of surrounding tissue and structure was often found in macroadenoma. In terms of octreotide inhibition test, the range of 24h TSH inhibition rate was roughly the same in the two groups (37.4%-91.8% and 46.5%-94.1%, respectively). Mixed adenoma was rare among all the pathologically confirmed cases. In Chinese PLA General Hospitals, TSH immunoreactive negative neoplastic cells were found in 3 of 8 cases, and octreotide scanning showed negative in 2 of 12 cases.Conclusions Patients with TSH-omas in the two hospitals show similarities but also some significant differences in the clinical features. Overall, the domestic patients with TSH-omas are diagnosed without gender difference according to the reports in China. The mean age at diagnosis is significantly younger than that in foreign data. Microadenoma is more common in females, while macroadenoma is more common in males. Serum TSH levels can be normal in patients with TSH-omas. Immunostaining and/or octreotide scanning for TSH can be negative.

Expression of Notch1, Notch3 and Hes1 in gastrointestinal stromal tumors and their clinical significance / 重庆医学

Objective To investigate the expression of Notch1,Notch3 and Hes1 in gastrointestinal stromal tumors(GIST) and their clinical significance.Methods Quantitative real-time polymerase chain-reaction(Q-PCR) and Western blot were applied to detect the mRNA and the expression of Notch1,Notch3 and Hes1 in 135 matched GIST specimens and adjacent tissues.Meanwhile,the expression of Notch1,Notch3 and Hes1 was detected by immunohistochemistry,and the relationship between their expression and clinicopathological factors in GIST patients was analyzed.In addition,a total of 40 wild type mice(WT) and Notch1 knockout mice(KO) was divided into WT group,KO group,WT+ GIST group and KO+GIST group,and the expression of Notch1,Notch3 and Hes1 in each group was detected.Results Compared with adjacent tissues,the mRNA andthe expression of Notch1,Notch3 and Hes1 were up-regulated in GIST tissues(P＜0.05).The positive rates of Notch1,Notch3 and Hes1 in the GIST specimens (59.26 ％,65.19 ％ and 62.22 ％) were higher than those in the adjacent tissues(17.780％,22.22 ％ and 17.78 ％),and the difference was statistically significant(P＜0.05).Statistical analysis showed that the expression of Notch1 was significantly correlated with the NIH grade of GIST(x2 =8.532,P=0.002);the expression of Notch3 was significantly related with tumor metastasis of GIST (x2 =7.532,P=0.003);the expression of Hes1 was significantly associated with the tumor size of GIST(x2 =6.781,P=0.012).The expression of Notch1,Notch3 and Hes1 was higher in WT+GIST group compared to the expression found in WT group(all P＜0.05).There were no significant differences in the expression of Notch1,Notch3 and Hes1 between WT+ GIST group and KO+GIST group.The expression of Notch1,Notch3 and Hes1 was lower in KO+ GIST group compared to the expression found in WT+GIST group(all P＜0.05).Conclusion The expression of Notch1,Notch3 and Hes1 related to Notch signaling pathway is elevated in GIST tissues,and the activation of Notch signaling pathway may play an important role in the occurrence and progression of GIST.

Effect of different clinical interventions for gastric tube in patients undergoing gastrointestinal operations on the risk of postoperative complications and recovery of gastrointestinal tract / 实用医学杂志

Objective To assess the effect of different clinical interventions for gastric tube in patients undergoing gastrointestinal operations for measuring the risk of postoperative complications and recovery of gastrointestinal tract. Methods A total of 148 patients undergoing gastrointestinal operations were recruited and divided into Group A, B, C and D, with 37 cases in each group. All patients underwent perioperative management based on the concept of rapid rehabilitation surgery. Group A were not indwelled with gastric tube with routine method. Group B were indwelled with gastric tube with routine method and got nasogastric extubation 5 min before tracheal extubation. Group C were indwelled gastric tube with routine method and got nasogastric extubation 6 h after fully conscious of anesthesia. Group D indwell gastric tube with routine method and got nasogastric extubation 12 h after fully conscious of anesthesia. The parameters including time of the first passing of flatus, defecation and resuming peristaltic sound after operation between the groups were compared. Vasoactive Intestinal Peptide (VIP), Motilin (MTL) and Glucagon (GLU)before the operation, and at the 1st, 3rd and 7th day after operation were measured by radioimmunoassay. Results Time of the first passing of flatus, defecation and resuming peristaltic sound after operation showed a rising trend from Group A to Group D. The difference in time of the first passing of flatus was not significant (P>0.05), time of defecation and resuming peristaltic sound after operation in Group A were significantly shorter (P0.05). VIP in Group A at the 3rd day after operation was significantly lower than those in other 3 groups , with the increasing of time for indwelling tubes. VIP showed a rising trend. MTL showed a decreasing trend with the increasing of time for indwelling tubes at 3rd and 7th day after operation. GLU in Group A was the highest (P0.05). Nausea and vomiting, anastomotic fistula, intestinal obstruction, abdominal distension in 4 groups showed no significant differences (P>0.05). Conclusion Avoidance of gastric tube in gastrointestinal operations can benefit the postoperative recovery of gastrointestinal tract , reduce pharyngeal discomforts and pulmonary infections. For patients with indwelled gastric tube, the time for indwelling tubes should be shorten, in order to speed up the recovery process and improve the safety of the patients.

Effect of compound Xueshuantong capsule in treatment patients of cataract with proliferative diabetic retinopathy / 中国生化药物杂志

Objective To discuss effect of compound Xueshuantong capsule in in treatment patients of cataract with proliferative diabetic retinopathy.Methods 60 cases of cataract patients with proliferative diabetic retinopathy from February 2015 to February 2016 in our hospital were selected,according to random number table method divided into observation group (n=30) and control group (n=30).The patients in both groups were given basic medical treatment of diabetes,the patients in observation group were treated with Xueshuantong capsule before cataract surgery,continue treatment for three months.The total effective rate of treatment was compared between the two groups,the results of fundus fluorescein angiography and macular thickness before and after treatment were compared,comparison the levels of VEGF in the aqueous humor of the two groups after the treatment. Results The total effective rate of treatment in observation group was significantly higher than control group (P<0.05).After treatment, the number of hemangiomas in the observation group was significantly less than that in the control group (P<0.05),the area of exudation was significantly smaller than that of the control group (P<0.05),the macular thickness of the observation group was significantly lower than the control group (P<0.05),the VEGF content in aqueous humor was significantly lower than that in control group (P<0.05).Conclusion Compound Xueshuantong capsule can significantly improve the retinopathy of cataract patients with proliferative diabetic retinopathy,has a significant effect on decreasing VEGF concentration in aqueous humor and reducing macular edema .

Epidemiological features and risk factors of spontaneous abortion among rural Tibetan women at childbearing age / 中华流行病学杂志

Objective To study the current status and risk factors of spontaneous abortion of women with Tibetan ethnicity at reproductive age in rural areas.Methods Pregnant women who lived in fibet were interviewed on their former reproductive history and being followed on the outcomes of pregnant from 2006 to 2012.Generalized Poisson regression model was used to explore the influencing factors of spontaneous abortion.OR value of the research factors was estimated and its 95％ confidence interval counted.Results There were 1 557 pregnant women under this study,with a total number of 2 687 pregnancies and 2 382 productions.171 women underwent spontaneous abortion,with a total number of 204 times,93 women had histories of abortion,with a total number of 101 times.Among all the Tibetan pregnant women,the ratio between spontaneous abortion and pregnant women was 7.6％ while the rate of spontaneous abortion was 7.9％.Ratio between the number of women who had experienced spontaneous abortion and the total number of women under survey was 11.0％.Pregnancy appeared the important reason on spontaneous abortion.The risk of having spontaneous abortion would increase among women who had more than 3 pregnancies.Results from Poisson regression analysis revealed that the odds ratio (OR) value before the adjustment was 3.921 (95％CI:2.553-6.021) but after the adjustment,it increased to 4.722 (95％CI:2.834-7.866).The increase of production time could reduce the risk of spontaneous abortion in women of childbearing age.Risks related to spontaneous abortion were associated with the number of pregnancies.Women seemed to have lower risk for spontaneous abortion after 2009,with OR value as 0.419(95％CI:0.285-0.616) before,compared to aOR value as 0.580 (95％CI:0.380-0.885) after the adjustment Social-demographic characteristics was not found to be particularly associated with the occurrence of spontaneous abortion.Conclusion Rate of spontaneous abortion among Tibetan women at childbearing age was not particularly high when comparing to those women living in the plain area such as Shaanxi.However,in order to further reduce the incidence of spontaneous abortion among Tibetan women,approaches should include the following items:strengthening maternal health care,extending the spacing of pregnancy and reducing the frequency of pregnancy.

Growth pattern of Tibetan infants: one-year follow-up study after birth in rural Tibet / 中华流行病学杂志

Objective To investigate the growth pattern of rural Tibetan children in the first year after birth.Methods In rural area of Lhasa,Tibet,252 subjects were recruited and their weight,length were measured longitudinally from birth to 12th months of age.Frequency of monitoring reached 5 times in total and Ponderal index (PI) was calculated for each visit.Mixed model was used to analyze the changes of length and weight by gender after controlling for birth weight.Results Birth weight and length showed great influence on children' s growth (weight:β =-0.681 9,P＜0.000 1,length:β =-0.957 1,P＜0.000 1).Weight and length of Tibetan male infants at each age point were lower than WHO new standard on growth and the Reference from 2005 National Survey on growth of children in China.The gap seemed widened by time but the gap between Tibetan female infants and Chinese standard narrowed 6 months after birth.Data showed that the higher PI of Tibetan infants than that of other Chinese infants which might infer that Tibetan infants had a more solid body mass under their own height.Conclusion The growth pattern of Tibetan infants might have its own feature.Tibetan infants appeared to have had higher PI,which was contradictory to the general conclusion that poor growth and development status had been seen in Tibetan children.