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Objective: To analyze the consistency of plasma circulating tumor DNA (ctDNA) and tumor tissue DNA in detecting KRAS/NRAS/BRAF/PIK3CA gene mutations in patients with advanced colorectal cancer, and to explore the factors affecting the consistency. Methods: Patients with advanced colorectal cancer who were treated in Zhongshan Hospital Fudan University from December 2018 to May 2020 were enrolled. The results of plasma and tissue gene detection, clinicopathological information and treatment were collected. The consistency and influencing factors of plasma and tissue KRAS/NRAS/BRAF/PIK3CA status were analyzed. Results: The patients enrolled in this study all received plasma gene detection. The mutation rates of KRAS, NRAS, BRAF and PIK3CA in plasma were 27.30%, 2.42%, 6.06% and 9.70%, respectively. Among them, 128 patients underwent tissue gene testing, and the mutation rates of KRAS, NRAS, BRAF and PIK3CA were 30.47%, 2.34%, 7.03% and 3.13%, respectively. The overall coincidence rate of KRAS/NRAS/BRAF/PIK3CA status by plasma and tissue was 62.50% (Kappa=0.200, P=0.023). Univariate analysis showed that the consistency of gene detection was higher in newly diagnosed untreated group and liver metastasis group, but lower in lung metastasis group. Conclusion: Our real-world study found that there are some differences in KRAS/NRAS/BRAF/PIK3CA status between plasma and tissue. Anti-tumor therapy and metastatic sites may be important factors affecting the inconsistency.

Objective: To investigate the clinical characteristics, treatment and prognosis of optic neuropathy associated with varicella zoster virus (VZV). Methods: Five cases of optic neuropathy associated with VZV infection from Department of Neurology between January 1, 2014 and March 31, 2019 were retrospectively collected. The clinical manifestations, treatment and prognosis were analyzed. Results: There were 7 eyes involved in 5 cases, 3 cases (3/5) involved only one eye, and 2 cases (2/5) involved both optic nerves. During the follow-up time, no recurrence was found. Severe visual impairment occurred in 4 eyes (4/7) and non-severe visual impairment in 3 eyes (3/7). Visual acuity improved significantly in 1 eye (1/7), turned better in 2 eyes (2/7), and remained unchanged in 4 eyes (4/7). In acute phase, abnormal signals of optic nerve and/or sheath were observed on MR images. Case 3 received antiviral and hormone therapy on the second day after the onset of the disease, and the visual acuity recovered well; the other 4 cases had poor prognosis. Conclusions: Head and face VZV infection can cause serious optic neuropathy, leading to severe visual dysfunction, and poor prognosis, but recurrence is rare. Early intravenous administration of antiviral drugs (acyclovir is the best) and hormones are recommended for VZV infection in this area. It is best to use drugs within 72 hours in order to avoid and reduce secondary optic neuropathy as far as possible.

Objective: To characterize the ocular saccadic abnormality in neuromyelitis optica spectrum disorder (NMOSD) patients, and explore the relationship between ocular saccadic abnormality and the overall disability and visual function state. Methods: For the 110 consecutive NMOSD patients who visited the Department of Neurology of Beijing Tongren Hospital from July 2015 to July 2017, a 120 Hz spatial resolution infrared video nystagmus system was used to perform a quantitative horizontal saccade examination. All patients were assessed for overall disability status using the extended disability status scale (EDSS). The subjective visual function status was evaluated using the National Eye Institute-Visual Function Questionnaire (NEI-VFQ 25) and the 10-item neuro-ophthalmic supplement questionnaire (Suppl. 10). Results: A total of 68 (61.8%) of 110 NMOSD patients had horizontal saccadic abnormalities, including 50 cases (45.5%) with abnormal saccade latency, 34 cases (30.9%) with abnormal saccade accuracy and 22 cases (20.0%) with abnormal speed. Patients with abnormal saccade had more intracranial lesions and higher EDSS scores than those with normal eye movements ( P= 0.006 and P< 0.001, respectively). Patients with abnormal saccade had lower Supp.10 scores than the normal patient ( P= 0.004), while there was no significant difference of NEI-VFQ 25 scores between the two groups ( P= 0.079). Conclusions: The horizontal saccadic abnormality is common in the NMOSD patients, and the overall disability status and visual function-related quality of life are worse. Quantitative horizontal saccade examination can provide important information on intracranial lesions and neuronal function impairment, and thus it should be emphasized in clinical settings.

Objective: To investigate the clinical features, imaging findings and prognosis of idiopathic intracranial hypertension (IIH) patients complicated with iron deficiency anemia (IDA). Methods: A total of 307 cases of IIH patients hospitalized in Beijing Tongren Hospital were retrospectively screened between January 1, 2011 and February 28, 2018. There were 49 anemia cases (15.96%) and 45 IDA cases (14.66%), respectively. Finally, 36 IDA patients were enrolled. The clinical characteristics, imaging findings, treatment and prognosis of these patients were analyzed. Results: IIH combined with IDA was more common in women of childbearing age (34/36). There were 30 obese and overweight cases (83.33%), with multiple subacute or chronic course of disease. The visual symptoms in the early IIH patients were first diagnosed in the Department of Ophthalmology. The first symptom was headache with/without visual symptoms (27 cases (75%)). Head MRI detected empty sella or partial empty sella, and 2 cases of venous sinus thrombosis were found in DSA examination. Of the 34 female patients, 24 had simple menometrorrhagia or menstrual disorder. All patients were given methyl acetate to reduce the intracranial pressure and iron therapy. Five patients received low molecular weight heparin-warfarin sequential treatment, 5 cases underwent gynecologic surgery and 2 male cases received hemorrhoid operation. There were 7 cases underwent lumbar cisterna-peritoneal shunt for visual impairment. During the follow-up, intracranial pressure decreased and visual function of patients improved significantly. Conclusions: IIH is frequently found in obese or overweight women at childbearing age and IDA may be an important cause of IIH. IIH can cause serious irreversible visual impairment. Therefore, early identification and active treatment should be performed. Correction of anemia can significantly improve the clinical symptoms of IIH. Operation should be employed for IIH patients with poor visual function or rapid progress, in order to reduce intracranial pressure and improve prognosis as soon as possible.

Objective: To analyze the clinical and immunological characteristics of acute severe bilateral optic neuritis, and to explore the predictive factors of vision outcome and relapse so as to save visual function and avoid or alleviate vision disability. Methods: Forty-eight inpatients confirmed with acute severe bilateral optic neuritis from January 2013 to June 2015 were included and followed up. The clinical features, immunological findings, optic nerve imaging, visual function outcome and predictors of relapse were statistically analyzed. Results: Acute severe bilateral optic neuritis accounted for 7.3% of the total number of optic neuritis in the same period. There were 35 cases (72.9%) with monophasic course, and 13 cases (27.1%) with recurrence or other central nervous system involvement during the follow-up period; 11 (22.9%) in 48 patients with positive AQP4-IgG; AQP4-IgG-positive patients had a higher recurrence rate ( P <0.001) and poorer visual function prognosis ( P =0.034) than antibody-negative patients; the baseline visual acuity ( P =0.004), early treatment response ( P =0.012) and number of involved optic nerve segments ( P =0.016) were associated with end point visual function. Positive AQP4-IgG( OR 13.486, 95% CI 1.971-16.263)and combining with other autoimmune antibodies ( OR 5.591, 95% CI 1.502-15.621)were independently associated with relapse. Conclusions: Acute severe bilateral optic neuritis is not unusual and may cause blindness or visual disability. The positive rate of AQP4-IgG and the recurrence rate of the disease are low in our study. The necessity for long-term immunotherapy requires individual consideration. The baseline visual acuity, involved segment number of optic nerve and response to early treatment are associated with prognosis of visual function. Patients with AQP4-IgG positive and other autoimmune antibodies are easy to relapse. Whether the antibody-negative bilateral optic neuritis is a heterogeneous disease and the relationship with classic NMO or NMOSD deserve further research.

Objective: To classify different causes of cavernous sinus lesion in patients with ophthalmoplegia and analyze their clinical and imaging features. Methods: We confirmed the etiological diagnosis of 137 hospitalized ophthalmoplegia patients with cavernous sinus lesion retrospectively from January 2005 to January 2014 in the Department of Neurology of Beijing Tongren Hospital.The diagnosis was made according to clinical feature, laboratory test, imaging studies and pathology.The clinical data of these patients were analyzed and compared among different groups. Results: Fifty-one cases (37.2%) were confirmed as inflammatory diseases of cavernous sinus, which were the most common cause in 137 patients.Early stage pain ( OR 5.591, 95% CI 1.703-18.401) and involvement of oculomotor nerve ( OR 4.902, 95% CI 1.015-24.630) were independently associated with inflammatory diseases.Forty-three cases (31.3%) were confirmed to have tumor, which was the second cause of cavernous sinus lesions, and meningioma was the most common tumor.The second branch of trigeminal nerve involvement was independently correlated ( OR 1.017, 95% CI 1.005-1.071) with tumor.The percentage of male ( OR 3.506, 95% CI 1.362-8.765) was significantly higher in 28 cases (20.4%) with cavernous sinus vascular lesions.Cavernous sinus infectious diseases were seen in 15 cases (10.9%), and fungal infection was the most common, mostly secondary to sinus infection. Conclusions: The common causes of cavernous sinus lesion include cavernous sinus inflammatory diseases, neoplastic diseases, vascular diseases and infectious diseases, and inflammatory diseases is the most commonly seen cause in this group of patients.Obvious facial sensory disturbances and the second branch of trigeminal nerve involvement are independent associated with tumor.The early course of pain and involvement of oculomotor nerve are associated with inflammatory diseases.Optimization of MRI examination method can better identify the cavernous sinus lesions.

Objective: To study the characteristics of blood lipids levels' change during pregnancy, and to discuss the relationships between the blood lipid level and the age, gestational hypertension, gestational diabetes and other pregnancy complications., Methods: From January to September 2015, we enrolled 2 907 pregnant women admitted to our hospital for regular checks as control group, 190 cases in gestational hypertension group, 258 cases in gestational diabetes mellitus group. The control group was divided into first trimester (≤12 w) second trimester (20 to 26 w) and third trimester (≥28 w) groups; in second trimester group, patients were further divided into the certain age group (<35years old) and elderly group (≥35 years old); blood lipid levels including serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) were detected in all groups., Results: (1) Blood lipids levels varied as pregnancy proceeded. TG level increased most significantly, followed by TC, LDL-C level. However, HDL-C level slightly decreased in third trimester comparing with first and second trimester stage, the difference was statistically significant (P< 0.05); (2) serum TC, TG and LDL-C level in second trimester were significantly higher in the certain age group than in the elder group (P< 0.05); (3) in gestational diabetes mellitus group, serum TC, TG, LDL-C levels were significantly higher in first and second trimester than those in the control group (P< 0.05); (4) in gestational hypertension group, serum TC, TG, LDL-C levels were significantly higher in third trimester than those in the control group (P< 0.05); HDL-C level was lower in the gestational hypertension group than in the control group, and there was statistically significant difference (P<0.05)., Conclusions: The blood lipid levels in pregnancy increase gradually as the gestational weeks increase, which can be explained as a normal physiological phenomenon. Elder pregnancy, gestational hypertension and gestational diabetes mellitus patients usually have obvious blood lipid disorder, therefore, it is very important to monitor the blood lipid level during pregnancy stages for predicting and early intervention of pregnancy complications such as gestational diabetes mellitus and gestational hypertension.

Objective: To investigate the role of heme oxygenase-1 (HO-1) in the oxidative stress damage of intestinal mucosa barrier disruption in patients with malignant obstructive jaundice (MOJ)., Methods: Fifteen jaundiced patients with malignant biliary obstruction undergoing endoscopic retrograde cholangiopancreatography (ERCP) examination or treatment were enrolled. The control group was comprised of 10 healthy subjects with gastroscopy and 10 patients with non-jaundiced biliary obstruction. Patients were subjected to duodenal biopsy to assess the intestinal oxidative stress as estimated by lipid peroxidation (malondialdehyde) and activity of superoxide dismutase (SOD). Apoptosis of epithelial cell was examined by TdT-mediated dUTP-biotin nick end labeling. Immunohistochemistry and Western blotting were employed to examine the distribution and expression of HO-1 proteins in intestinal mucosa., Results: MOJ jaundiced patients presented high levels of intestinal oxidative stress with a significantly increased level of lipid peroxidation [(1.79 +/- 0.24) vs (1.09 +/- 0.28) vs (1.18 +/- 0.32) nmol x mg(-1) x prot(-1), P = 0.041] and a decreased SOD activity [(303 +/- 10) vs (398 +/- 11) vs (406 +/- 11) nmol x mg(-1) x prot(-1), P = 0.017]. The apoptotic rate of intestinal epithelial cells was significantly higher in jaundiced group than in non-jaundiced control group. Apoptotic index was (69.1 +/- 5.9)%, (28.6 +/- 3.5)% and (10.2 +/- 2.5)% respectively (P < 0.01). The staining of HO-1 was predominantly localized in cytoplasm. In jaundiced patients, HO-1 was obviously elevated than those in the control group (HO-1 optical density 0.28 +/- 0.04 vs 0.20 +/- 0.04 vs 0.13 +/- 0.05) (P < 0.01). Similar outcomes were obtained by quantitative analysis of Western blotting images [HO-1/GAPDH (10.7 +/- 0.7)% vs (7.6 +/- 0.5)% vs (3.9 +/- 0.4)%, P < 0.01]., Conclusion: MOJ induces intestinal oxidative stress and it may be a key contributing factor to intestinal barrier failure in the patient population. HO-1 protein level is rising with the progression of obstruction. Perhaps HO-1 has a protective effect upon MOJ through anti-oxidative damage.

Objective: To investigate the effect of high thoracic epidural anesthesia on ventricular remodeling and cardiac function in rats with heart failure induced by myocardial infarction, and to investigate their mechanism., Methods: Rats that had been established successively model were randomly divided into S group (n = 12), HTEA group and CHF group (24/group). 9.0 g/L normal sodium 100 microl/kg was injected to epidural cavity twice a day separately in group S and group CHF. 1.25 g/L bupivacaine 100 microl/kg was injected to epidural cavity twice a day in group HTEA. Epidural injection was started 24 hrs after the epidural surgery and continued 4 weeks. Then the change of cardiac function was observed by using echocardiogram. The ratio of heart weight to body weight (HW/BW) and the ratio of left ventricular weight to body weight (LVW/BW) were measured. Noninfarct ventricular tissue were stained with hematoxylin-eosin (HE) and Masson's trichrome respectively. beta(3)-adrenoceptor levels and eNOS levels were detected with reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry., Results: LVEDD and LVESD were significantly decreased in the group HTEA compared with group CHF (P < 0.01), while LVEF% and LVFS% were significantly increased (P < 0.01). The ratios HW/BW and LVW/BW were significantly increase in the group CHF compared with the group S (P < 0.01), but they were limited in the group HTEA (P < 0.01). Hypertrophy and edema, degeneration and necrosis of myocytes can be seen in rats with CHF, as well as muscle fibers disruption and collagen fiber increase, while the pathological amorphous were attenuated in HTEA rats. beta(3)AR and eNOS mRNA levels were significantly decreased in the group THEA compared with the group CHF., Conclusions: These results indicate that HTEA could ameliorate ventricular remodeling and cardiac function in rats with heart failure induced by myocardial infarction. The mechanism could involve decreases of beta(3)AR expression in rats of heart failure.

Objective: To evaluate the effects of nerve growth factor (NGF) on the proliferation and apoptosis of hepatic stellate cells (HSCs) of fibrotic rat., Methods: HSCs of fibrotic rat were incubated in medium with different concentrations of NGF (50 ng/ml, 100 ng/ml, and 150 ng/ml respectively) or without NGF for 24, 48 and 72 hours respectively. The proliferation rate of the HSCs was determined by MTT assay. Apoptotic HSCs were detected by TUNEL method. The apoptotic rate of HSCs was studied by flow cytometry. The conformation of HSCs was observed by microscopy., Results: (1) MTT method indicated that the proliferation rates of the HSCs induced with different concentrations of NGF for 24 hours was significantly reduced compared with that of the control group (0.77 +/- 0.03, all P < 0.05). The proliferation rate of the HSCs treated with NGF of the concentration of 100 ng/ml for 24 hours was the lowest (0.63 +/- 0.02, P < 0.05). (2) The proliferation rate of the HSCs treated with NGF of the concentration of 100 ng/ml, the most appropriate concentration, increased time-dependently, and the proliferation rate at the 72 th hour was the lowest in comparison with that of the control group (0.48 +/- 0.03 vs 0.89 +/- 0.01, P < 0.05). (3) After stimulation of the HSCs by NGF of the concentration of 100 ng/ml for 24 hr, TUNEL method showed a significant increased apoptotic rate of HSCs compared with the control group (10.2% +/- 1.2% vs 1.6% +/- 0.1%, P < 0.05). Meanwhile, flow cytometry showed an apoptotic rate of 6.2% +/- 0.2% among the HSCs in the experimental group, but no apoptosis in control group. (4) Microscopy did not show significant morphological change in the HSCs with the proliferation inhibited., Conclusion: NGF can induce apoptosis of activated HSCs. The mechanism may be the interference with the apoptotic pathway.

Acute volume loading produced by autogenous reinfusion of ascitic fluid provides an ideal volume expansion model for studying hormonal regulation and it was carried out in 10 cirrhotic patients with massive ascites. The basal plasma ANP level in the cirrhotic patients with ascites was 1776.00 +/- 160.72 ng/L, which was significantly elevated as compared with the level in normal controls (378.36 +/- 39.58 ng/L, P less than 0.01), PRA was significantly higher in patients with ascites (5.13 +/- 0.18 micrograms/l/h) than in healthy volunteers (1.46 +/- 0.31 micrograms/l/h, P less than 0.01). During reinfusion of ascitic fluid there was a significant natriuresis and diuresis; ANP rose from a basal mean value to a peak value of 2166.00 +/- 195.70 ng/l (P less than 0.05) at periinfusion. Subsequently, ANP dropped at 1 hour after infusion (1819.00 +/- 165.92ng/L, P less than 0.05), PRA dropped progressively from a mean basal level to that of 2.48 +/- 0.58 micrograms/l/h (P less than 0.05) at periinfusion. These data demonstrate that there is no evidence for absolute deficiency of ANP in cirrhosis with ascites. The immediate diuresis and natriuresis were associated with a rise in ANP, but the sustained renal consequences may be possibly connected with suppression of RAAS.