[Epidemiological characteristics of spontaneous subarachnoid hemorrhage cases in Shandong province].

Objective: To investigate the characteristics and trends of spontaneous subarachnoid hemorrhage (SAH) in Shandong province. Methods: In this study, SAH incidence data of residents from 2012 to 2021 were collected from the chronic disease monitoring information management system of Shandong province, including the basic information of outpatient, emergency or inpatient cases and out-of-hospital deaths (name, gender, ID number, address, etc.) and disease diagnosis information (disease diagnosis, date of onset, date of diagnosis, etc.). The crude incidence rate and age-standardized incidence rate were used as indicators to describe the incidence of SAH in different gender, age groups and regions (urban and rural areas). Joinpoint regression was used to analyze the variation of incidence rate and age by year. The rate difference decomposition method was used to estimate the contribution of population aging to the increase of SAH incidence. Global and local spatial autocorrelation analysis was performed using DeoDa 1.12 software. Results: From 2012 to 2021, a total of 11 629 cases of SAH were reported from 19 provincial monitoring sites in Shandong province. Among them, 54.11% (6 293 cases) were female and 91.87% (10 684 cases) were≥45 years old. The reported crude incidence rate increased from 5.26/100 000 to 9.50/100 000, with an average annual increase of 7.75% (Ztrend=7.30, Ptrend<0.001), and the standardized incidence rate also showed an upward trend (Ztrend=3.92, Ptrend=0.004). The crude incidence rate of women was higher than that of men in all years (all P values<0.05), and the standardized incidence rate of women was higher than that of men in all years except in 2012 and 2021 (all P values<0.05). In 2012, the crude incidence and standardized incidence of urban residents were lower than those in rural areas (P<0.05); from 2013 to 2017, the urban incidence was higher than that in rural areas; and after 2018, the rural incidence exceeded the urban incidence again (all P values<0.05). The median age of onset of SAH increased from 61.9 years in 2012 to 67.2 years in 2021. The age of onset of SAH in men was lower than that in women in all years (all P<0.05), and there was no significant difference between urban and rural residents in most years (P>0.05). The incidence of SAH increased with age (Ptrend<0.001), with a low incidence reported in residents aged<45 years and a rapid increase in residents aged≥45 years. According to the seasonal decomposition, the incidence of SAH had three small peaks in January, March to May and October to November. From 2013 to 2021, the contribution of aging population to the increase of crude incidence of SAH increased from 27.86% to 43.68%. The global spatial autocorrelation analysis showed that the incidence of SAH was in an obvious spatial aggregation distribution (Moran's I>0, P<0.05). Local spatial autocorrelation analysis showed that the counties with high incidence were mainly concentrated in Dezhou City in northwest Shandong Province and Heze city in southwest Shandong province. Conclusions: The crude incidence rate of SAH in Shandong province is increasing, with spatial clustering and seasonal clustering. Residents aged 45 years and older, female residents, and rural residents are at high risk of developing SAH, so targeted prevention and control measures should be taken for high-incidence seasons, high-risk groups, and high-incidence clustered areas.

[Clinical evaluation methods for craniovertebral junction abnormalities].

Craniovertebral junction malformation is a congenital malformation located in the foramen magnum and upper cervical spine, including bone and nerve malformation, resulting in motor and sensory disorders, cerebellar and lower cranial nerves, etc. The evaluation methods of clinical symptoms and efficacy of craniovertebral junction malformation are important for the surgical indications and effects, mainly including the evaluation of clinical symptoms and the quality of life. At present, the commonly used methods in clinical work and literature are the Japanese orthopaedic association scores, visual analogue scales, 36-item short-form health survey, etc. Most of these clinical evaluations are not aimed at craniovertebral junction diseases but focus on the description of a certain type of clinical symptoms. Chicago Chiari outcome scale and syringomyelia outcome scale of Xuanwu hospital are dedicated to Craniovertebral junction malformation, but more clinical studies are needed to prove their effectiveness. Based on the literature reports, this article reviewed the previous clinical evaluation methods of craniovertebral junction malformation and discusses their applications and limitations.

[The measurement and application of imaging evaluation parameters for cranio-cervical junction osseous and neural abnormalities:a review].

Cranio-cervical junction (CVJ) anomalies encompass a spectrum of bone,soft tissue,and neural structural abnormalities,including basilar invagination,platybasia,atlantoaxial dislocation,tonsillar herniation,and occipito-cervical fusion.Given the frequent coexistence of these anomalies and the intricate anatomical variations involved,precise imaging techniques and evaluation parameters are crucial for accurate disease characterization and treatment assessment.Since the 1930s,various parameters,such as the McRae line,Chamberlain line,Wackenheim line,and clivo-axial angle,have been widely employed for evaluating basilar invagination and platybasia.The advent of MRI and CT has further expanded the repertoire of parameters,including sagittal tilt,coronal tilt,medullary spinal angle,and intricate multi-axis evaluation systems.In this review,we summarize the relevant imaging parameters and their corresponding measurement techniques from previous literature,emphasizing high-sensitivity,consistent,and evidence-based parameters.This study aims to provide valuable insights for the imaging evaluation of CVJ anomalies.

[Change of innate lymphoid cell subsets in peripheral bloods and ascites in liver cirrhotic patients complicated with spontaneous bacterial peritonitis].

Objective: To investigate the change of innate lymphoid cells (ILC) subsets in peripheral blood and ascites in liver cirrhotic patients complicated with spontaneous bacterial peritonitis (SBP). Methods: The data of 62 patients with liver cirrhosis admited to the Zhumadian Central Hospital from November 2019 to November 2020 were analyzed. Among them, 41 cases were complicated with untainted ascites (untainted ascites group), while the other 21 cases were complicated with SBP (SBP group). Meanwhile, 20 cases of controls who received healthy examination in the same period were also enrolled (control group). Peripheral blood mononuclear cell (PBMC) was isolated from peripheral blood of all patients and controls. Mononuclear cell in ascites was isolated from patients with liver cirrhosis. The percentage of ILC1, ILC2, and ILC3 subsets in PBMC and mononuclear cell in ascites were measured by flow cytometry. CD3-CD19-CD20-CD14- cells (lin-cells) were purified from ascites and were stimulated with lipopolysaccharide (LPS) for 24 h. The transcription factor T-bet, GATA3, and RORγt mRNA relative level in lin-cells was semi-quantified by real-time PCR. Cytokine level in the supernatants was measured by enzyme linked immunosorbent assay. Differences of ILC subsets in peripheral blood and ascites were compared among groups. Results: There were twenty-nine males and twelve females in untainted ascites group, aged M(Q1,Q3) 49(33, 78) years. There were twelve males and nine females in SBP group, aged 50(37, 76) years. There were eleven males and nine females in control group, aged 48(32, 69) years. lin-CD45+CD161+CD127+ ILC cells could be detected in both peripheral blood and ascites. There was no significant difference in total ILC percentage within PBMC among untainted ascites group, SBP group, and control group (P=0.235). There was also no significant difference of total ILC percentage within mononuclear cells in ascites between untainted ascites group and SBP group (P=0.232). The differences were not statistically significant of peripheral CD117-CRTh2-ILC1, CRTh2+ILC2, or CD117+CRTh2-ILC3 within peripheral ILC among untainted ascites group, SBP group, and control group (all P>0.05). ILC1 percentage in ascites was up-regulated in SBP group compared with untainted ascites group (35.69%±3.39% vs 26.40%±3.85%, P<0.001), while ILC2 in ascites was down-regulated in SBP group (36.83%±7.70% vs 48.35%±9.45%, P<0.001). There was no statistical difference in ILC3 percentage in ascites between the two groups (P=0.230). T-bet mRNA relative level and IFN-γ production by lin- cells from ascites were elevated in response to LPS stimulation in SBP group compared with untainted ascites group (both P<0.001). GATA3 mRNA relative level and IL-5/IL-13 secretion by lin-cells from ascites were reduced in SBP group compared with untainted ascites group (both P<0.05). There was no significant difference of RORγt mRNA relative level or IL-17/IL-22 expression between the two groups (both P>0.05). Conclusion: Peripheral ILC subsets do not change in liver cirrhosis patients with SBP. ILC1 percentage is up-regulated, and ILC2 percentage is down-regulated in ascites in liver cirrhosis patients with SBP.

[Surgical treatment strategy for difficult-reducible atlantoaxial dislocation].

Objective: To discuss the surgical strategy for difficult-reducible atlantoaxial dislocation. Methods: Clinical data of 82 patients with difficult-reducible atlantoaxial dislocation underwent surgical treatment in the Department of Neurosurgery, Xuanwu Hospital from January 2018 to February 2019 were retrospectively reviewed. Total of 32 men and 50 women were included, with a mean age of (41.8±12.9) years. Most cases (n=80) were treated with one-staged posterior atlantoaxial joint distraction and cage implantation, a few (n=2) underwent ventral decompression. All cases were followed up, postoperative improvement of clinical symptoms and radiology parameters were analyzed. Results: Of the patients, 80 cases (97.6%) received one-staged posterior atlantoaxial joint distraction and cage implantation; lateral facet joint bony fusion was found in 4 patients and was cut off with an osteotome. Transoral odontoidectomy was performed in 2 cases (2.4%) with fused atlanto-odontoid joint. All the patients were followed-up for (18.6±7.3) months. Postoperative CT showed complete reduction of ADI was achieved in 60 patients (75.0%). The ADI decreased significantly after the operation [(2.1±1.4) mm vs (5.0±1.5) mm, P<0.05]. The postoperative vertical distance between odontoid process and the Chamberlain line decreased significantly when compared with that before the operation [(3.9±3.8) mm vs (10.2±5.2) mm, P<0.05]. The mean JOA score at 6 months post operation improved significantly than that before the operation (13.7±1.5 vs 11.2±1.7, P<0.05). Seventy-five patients (93.8%) had atlantoaxial intra-articular bony fusion at 1 year follow-up. Conclusion: Most difficult-reducible atlantoaxial dislocations can be managed well by posterior one-staged atlantoaxial joint distraction and Cage implantation.

[Role of CT and MRI image fusion and computer assisted simulation technique in guiding type â ¢ and â £ primary pelvic sarcoma surgeries].

Objective: To explore the possible clinical benefits of CT/MRI image fusion and computer-assisted simulation techniques in guiding type Ⅲ and Ⅳ primary pelvic bone tumor surgeries. Methods: The clinic data of primary bone sarcomas patients treated at Department of Bone and Soft Tissue,Zhenghzhou University Affiliated Cancer Hospital from January 2019 to December 2021 were retrospectively analyzed. Based on whether the CT and MRI image fusion technique was utilized for tumor evaluation and surgical planning,the patients were divided into image fusion group (n=21) or control group (n=27). There were 7 male and 14 female patients included in the image fusion group, with the age of (37.0±10.4) years(range: 18 to 67 years). In the control group, there were 10 males and 17 females with the age of (39.7±15.2) years (range: 16 to 65 years). Both groups included osteosarcoma,chondrosarcoma and undifferentiated polymorphic sarcoma as the pathological diagnosis. Clinical information such as gender,age,pathological diagnosis,location of disease,and metastasis at diagnosis were collected. Surgical related information such as duration of surgery,blood loss,surgical margin,and wound complications were also obtained. Periodical follow-ups every 3 months were performed for all patients to monitor the status of local recurrence,distant metastasis,and survival information. Independent t test and χ² test were used for data comparison between groups. Results: Significant reduced duration of surgery was observed in the image fusion group in comparison with control group both in type Ⅲ and Ⅳ surgeries ((144.0±31.6)min vs. (248.2±56) min,t=-8.084, P<0.01); (173.0±42.0)min vs. (306.1±62.0)min, t=-4.518, P<0.01). Blood loss was significantly reduced in the image fusion group compared with the control group ((484.8±226.3)ml vs. (836.1±359.8)ml,t=-4.130, P<0.01). In addition, significant lower ratio of R1 margin and recurrence rates of type Ⅲ and Ⅳ surgeries were found in the image fusion group comparing with the control group (4.8%(1/21) vs. 22.2%(6/27), χ²=4.214, P=0.040; 4.8%(1/21) vs. 22.2%(6/27), χ²=4.214, P=0.040).In the image fusion group, there were 3 cases of incision infection, 1 of which underwent secondary debridement.And in thecontrol group there were 7 cases of incision infection, 3 of which underwent secondary debridement. There was no significant difference in the incidence of complications between the two groups (14.2%(3/21)vs. 25.9%(7/27), χ²=0.645, P=0.422). Up to the last follow-up, 1 patient died in the image fusion group and 2 patients died in the control group, the difference was not statistically significant (χ²=1.885, P=0.220). Conclusion: Compared with the traditional operation,the image fusion technique can significantly reduce the duration of surgery,blood loss and lower the recurrence rate by achieving better surgical margins.

[Posterior atlanto-axial intraarticular distraction technique as revision surgery to treat atlanto-axial dislocation associated with basilar invagination].

Objective: To examine the effect of posterior atlanto-axial intraarticular distraction technique as revision surgery for failed posterior fossa decompression in patients with basilar invagination(BI) and atlanto-axial dislocation(AAD). Methods: The clinical data of 13 cases of AAD accompanied with BI treated at Department of Neurosurgery, Xuanwu Hospital, Capital Medical University were retrospectively analyzed. There were 3 males and 10 females,aged (42.6±9.5) years (range:30 to 63 years). All cases had assimilation of atlas and once underwent posterior fossa decompression. Anterior tissue was released through posterior approach followed by cage implantation into facet joint and occipital-cervical fixation with cantilever technique. The clinical results were evaluated using Japanese Orthopedic Association scale(JOA) and the main radiological measurements including atlantodental interval (ADI), the distance of odontoid tip above Chamberlain line(DCL),clivus-canal angle(CCA) and the length of syrinx were collected. Paired sample t test was used to compared the data before and after operation. Results: All patients underwent surgery successfully, the mean surgical time was (187.7±47.4) minutes (range from 116 to 261 minutes). Twenty occipital condyle screws, 26 C2 pedicle screws and 3 occipital plates were implanted. Clinical symptoms improved in all patients. Twelve patients had complete reduction of basilar invagination and atlanto-axial dislocation, 1 achieved near completely reduction of basilar invagination. The postoperative ADI, DCL and CCA significantly improved((4.3±1.1) mm vs. (1.8±0.8) mm, (11.7±5.0) mm vs. (6.4±2.8) mm, (142.4±7.9)° vs. (133.3±7.9)°, all P<0.01).There were 5 cases with syringomyelia before surgery, and shrinkage of syrinx was observed 1 week after surgery in all cases. Eight patients achieved bone fusion 3 months after surgery, all patients achieved bone fusion 6 months after surgery. The JOA score increased from 12.8±2.3 before surgery to 14.8±1.3 one year after surgery, with statistically significant difference (t=4.416, P<0.01).No implant failure, spacer subsidence and infection were observed. Conclusion: In cases of failure posterior fossa decompression of basilar invagination and atlanto-axial dislocation, using posterior atlanto-axial intraarticular distraction and cantilever technique with cage implantation could achieve complete reduction and symptomatic relief.

[Preliminary study on time-dependent changes of intestinal tract and brain-gut axis in mice model of Parkinson's disease induced by paraquat].

Objective: To observe the intestinal time-dependent changes in Parkinson's disease (PD) mouse model constructed by intraperitoneal injection of paraquat (PQ) and to establish the brain-gut axis connection initially. Methods: In October 2019, 48 mice were randomly divided into treated group and control groups: treated 4-week (P-4) group, treated 6-week (P-6) group, treated 8-week (P-8) group, control 4-week (C-4) group, control 6-week (C-6) group, and control 8-week (C-8) group. The treated group was injected with 15 mg/kg PQ solution and the control group was injected with 0.9% saline (0.2 ml/20 g) by intraperitoneal injection twice a week. After the initial state (0 weeks) and the treatment at the end of 4, 6 and 8 weeks, the mood changes and motor functions of mice were assessed by neurobehavioral tests (open field test, pole climbing test, tail suspension test and elevated plus maze test) . And the number of fecal pellets for 1 h and water content were calculated to assess the functional status of the gastrointestinal tract. Western blotting experiments were performed to detect the expression levels of α-synuclein (α-syn) and tyrosine hydroxylase (TH) in the nigrostriatal region of the mouse brain, the tight junction markers zonula occludens-1 (ZO-1) and Occludin, the inflammatory markers of integrin αM subunit (CD11b) , inducible nitric oxide synthase (iNOS) , high mobility group box 1 (HMGB1) , interleukin-1ß (IL-1ß) , and the neuronal markers ßⅢ-tubulin and α-syn protein in the colon.Immunohistochemical staining was performed to detect the expression levels of colonic tight junction proteins ZO-1 and Occludin. Immunofluorescence staining was performed to detect the expression levels of TH in the substantia nigra region of the midbrain, and the co-localization of colonic intestine neuronal marker (ßⅢ-tubulin) and Ser129 α-syn in the colonic. Results: Compared with the initial state (0 weeks) and C-8 group, mice in the P-8 group had significantly higher pole climbing test scores and resting time, and significantly lower total active distance, mean active speed, percentage of open arm entry and 1 h fecal instances (P<0.05) . After poisoning, the 1 h fecal water content of model mice first increased and then decreased, the P-4 and P-6 groups were significantly higher than the simultaneous point control group, and the P-8 groups were significantly lower than the initial state (P<0.05) . Compared with control, P-4 and P-6 groups, the expression levels of ZO-1 and Occludin in the P-8 group were significantly decreased (P<0.05) . Compared with control group, the expression levels of CD11b and IL-1ß in the P-4 group were significantly increased (P<0.05) . Compared with control and P-4 group, the expression levels of CD11b, iNOS, HMGB1 and IL-1ß in the P-6 and P-8 groups were significantly increased (P<0.05) . Compared with the control and P-4 groups, the expression levels of ßⅢ-tubulin in the colon of mice in the P-8 group were significantly decreased, and the expression levels of α-syn and Ser129 α-syn were significantly increased (P<0.05) . The expression level of Ser129 α-syn in the colon of model mice was negatively correlated with the expression level of ßⅢ-tubulin (r(s)=-0.9149, 95%CI: -0.9771--0.7085, P<0.001) . Ser129 α-syn and ßⅢ-tubulin co-localization in the colonic intermuscular plexus region increased gradually with the time of exposure. Compared with the control, P-4 and P-6 groups, the expression level of TH in the nigrostriatal region of the brain was significantly decreased, and the expression levels of α-syn and Ser129 α-syn were significantly increased in the P-8 group (P<0.05) . Correlation analysis showed that the relative expression level of Ser129 α-syn in the nigrostriatal region of the brain was negatively correlated with the expression level of TH in the model mice (r(s)=-0.9716, 95% CI: -0.9925--0.8953, P<0.001) . Conclusion: The PD mouse model is successfully established by PQ, and the intestinal function of the model mice is reduced in a time-dependent manner. And on this basis, it is preliminary determined that the abnormal aggregation of α-syn may be an important substance connecting the brain-gut axis.

[Dynamic changes of locus coeruleus damage in Parkinson's disease-like mice induced by paraquat].

Objective: To observe the dynamic changes of brainstem locus coeruleus (LC) damage in Parkinson' s disease (PD) -like mice by paraquat (PQ) . Methods: In October 2019, 36 male C57BL/6 mice were randomly divided into the exposure group and the control group, with 18 mice in each group. The mice in the exposure group were given intraperitoneal injection of 15 mg/kg PQ, and the mice in the control group were given intraperitoneal injection of 0.9% saline, twice a week for 8 weeks. Neurobehavioral changes (pole climbing test, swimming test, open field test, tail hanging test, high plus maze test and water maze test) were observed at 4 weeks, 6 weeks and 8 weeks, respectively, and the changes of motor ability, emotion and cognitive function were evaluated. The brain tissue of mice were taken and stained with Hematoxylin-Eosin (HE) to observe the pathological changes of LC. Nissl staining was used to detect the changes of neuronal Nissl bodies in LC. Immunohistochemistry (IHC) staining was used to detect the expression of neuron nuclear antigen (NeuN) , dopamine (DA) neurons and norepinephrine (NE) neuron markers tyrosine hydroxylase (TH) , α-synuclein (α-syn) in substantia nigra (SN) and LC. The expression levels of NeuN, TH and α-syn in the midbrain and brainstem were detected by Western blotting. TUNEL staining was used to detect neuronal apoptosis in LC. Results: Compared with the 4th week of PQ exposure group, the time of pole climbing and swimming immobility were gradually increased, the ratio of open arm residence time of high plus maze test and the number of times of the platform and the residence time of platform quadrant in water maze test were gradually decreased (P<0.05) in the exposure group with the progress of exposure time. The results of HE and Nissl staining showed that the neurons in LC gradually arranged loosely, the nucleus were deeply stained, the cytoplasm was pyknosis, and the number of Nissl bodies gradually decreased (P<0.05) in the exposure group with the progress of exposure time. IHC results showed that the number of NeuN and TH positive cells in SN and LC of mice were gradually decreased, and the positive expression of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. Western blotting results showed that the expression levels of NeuN and TH in the midbrain and brainstem were gradually decreased, and the expression level of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. TUNEL staining showed that the apoptosis rates of neurons in LC were gradually increased (P<0.05) in the exposure group with the progress of exposure time. Conclusion: PQ induces progressive damage in the LC area of PD-like mice, which may be caused by the abnormal accumulation of pathological α-syn in the LC area.

[The 484th case:asthma, limb numbness, diplopia, headache].

A 47-year-old female who had a history of asthma and sinusitis in the past was admitted to hospital with limbs numbness and pain for ten days. The symptoms were aggravated for eight hours. On admission, significant peripheral eosinophilia was noted. Paranasal sinusitis and transient bronchiolitis were found by CT scan.Electromyogram demonstrated multiple mononeuropathy. Eosinophilia was indicated by bone marrow biopsy. The diagnosis of eosinophilic granulomatous polyangiitis(EGPA) was determined. The patient got better after applying glucocorticoid and cyclophosphamide.Later she developed abdominal pain and partial oculomotor nerve palsy, while her condition improved after continued immunosuppression and anticoagulant therapy. She was hospitalized for the third time because of headache. Subarachnoid hemorrhage was diagnosed after lumber puncture and cranial MRI+MRA+MRV and other examinations. She was relieved after conservative treatment. Subarachnoid hemorrhage with EGPA is rare. This case may improve physicians' understanding of EGPA complicated with subarachnoid hemorrhage.

[Effect of high-fat diet on respiratory function and diaphragm fibers in mice and its mitochondrial mechanism].

Objective: To investigate the effect of high-fat diet (HFD) on respiratory function and its mitochondrial mechanism in mice. Methods: Twenty 4-week-old healthy male C57BL/6 mice were divided by simple random grouping into two groups, 10 mice for each group. Mice were raised with normal diet (NFD) and HFD for 16 weeks, respectively, and weighed once every two weeks. At the end of the intervention, respiratory parameters were measured by whole-body plethysomography, serum and diaphragm tissue lipid species were measured, diaphragm tissue was stained to observe diaphragmmatic morphology, muscle fiber phenotype and mitochondrial ultrastructure. Real-time fluorescence quantitative PCR and immunoblotting were used to detect myosin heavy chain(MHC) and mitochondrial dynamics-related genes and protein expression. Results: The baseline body weights of NFD and HFD mice were (19.17±0.59) and (19.12±0.64) g, respectively, with no statistically significant differences (P=0.857). After 16 weeks of feeding, the body weight of mice in the HFD group was (41.28±2.21) g, which was higher than NFD group [(27.14±0.53) g, P<0.001]. The peak inspiratory flow rate, tidal volume and minute ventilation of mice in the HFD group were (5.72±0.64) ml/s, (0.23±0.04) ml and (97.49±21.68) ml, respectively, which were lower than NFD group [(7.70±1.52) ml/s, (0.31±0.07) ml and (129.99±28.87) ml, respectively, all P values<0.05]. Penh value was 1.16±0.07, which was higher than NFD group (0.98±0.09, P<0.001). The diaphragmatic triglyceride content of mice in the HFD group was (20.43±6.36) mmol/mg, which was higher than NFD group [(11.62±1.78) mmol/mg] (P=0.003), and lipid droplets were deposited in the diaphragm fibers. The percentage of MHC-Ⅰ muscle fibers in the diaphragm of mice in the HFD group was 13.33%±2.95%, which was lower than NFD group (19.20%±1.23%, P=0.034). The mitochondria of the diaphragm in the NFD group were arranged in rows with clear structures, while in the HFD group showed swelling, cristae breakage and vacuoles. The relative expression level of mitochondrial fusion protein 2 in the diaphragm of the HFD group was 0.61±0.16, which was lower than NFD group (1.28±0.03, P<0.001); the relative expression of mitochondrial dynamin-related protein 1 were 1.18±0.06 and 0.91±0.11, respectively, both higher than NFD group (0.61±0.07 and 0.60±0.04, respectively, P<0.001). Conclusion: HFD impairs respiratory function in mice by the mechanism associated with the MHC-Ⅰ muscle fibers decrease and the mitochondrial dynamics imbalance of diaphragm.

[Analysis of the trend and spatial clustering of gastric cancer deaths in Shandong Province from 1970 to 2013].

Objective: To investigate the distribution characteristics and trends of mortality and spatial aggregation of gastric cancer in Shandong Province from 1970 to 2013. Methods: The mortality data of gastric cancer from 1970 to 1974, 1990 to 1992 and 2004 to 2005 were collected from the first, second and third retrospective sampling survey of causes of death in Shandong Province, respectively. The mortality data of gastric cancer from 2011 to 2013 were collected from the all-cause surveillance data of Shandong Province. The crude mortality rate and age-standardized mortality rate were used to describe the death level of gastric cancer. The age-standardized mortality rate of Shandong Province was calculated based on Segi's world standard population, and the age-standardized mortality rate of counties (cities and districts) was calculated based on the Chinese population in 1964.The factors influencing the difference of gastric cancer mortality in different periods were decomposed by using the method of differential decomposition of mortality, and the contributions of population and non-population factors in different periods were estimated.Using ArcGIS 10.2 software, the death level of gastric cancer in different counties (cities and districts) in Shandong province from 1970 to 1974 and 2011 to 2013 were visualized. DeoDa 1.12 software was used for global and local spatial autocorrelation analysis. Results: The crude death rate and age-standardized death rate of gastric cancer in Shandong province increased firstly and then decreased during 1970-2013, and the crude death rate of gastric cancer increased from 18.33/100 000 in 1970-1974 to 28.51/100 000 in 2011-2013. Segi's age-standardized mortality rate for gastric cancer decreased from 20.94 per 100 000 in 1970-1974 to 18.17 per 100 000 in 2011-2013.From 1990 to 1992, from 2004 to 2005 and from 2011 to 2013, the contribution value of non-population factors to the increase of crude gc mortality was 95.59%, 48.45% and -20.57%, respectively, showing a continuous downward trend. The Moran's I index of crude mortality of gastric cancer in Shandong province from 1970 to 1974 and from 2011 to 2013 were 0.77 and 0.57, respectively, and the Moran's I index of age-normalized mortality was 0.75 and 0.44, respectively. Local autocorrelation analysis showed that there were 31 and 19 high aged-mortality areas of gastric cancer in 1970-1974 and 2011-2013 respectively, and 7 overlapping counties (cities and districts), 6 of which were located in Jiaodong area. Conclusion: The crude mortality and age-standardized mortality of gastric cancer in Shandong province increased first and then decreased from 1970 to 2013, and the distribution of gastric cancer mortality had obvious spatial aggregation and changed with time.

[Insulin-like growth factor-1 alleviates hepatocyte senescence by regulating intranuclear p53-progerin pathway].

To construct cellular senescence model by stimulating primary hepatocytes with hydrogen peroxide (H(2)O(2)). Primary hepatocytes were transfected with p53 siRNA, progerin siRNA or IGF-1 adenovirus vector. The number of SA-ß-Gal stained positive cells and the expression of p53 and progerin were detected. The results showed that p53 siRNA and progerin siRNA had knocked-down the expression of p53 and progerin, and had alleviated the hepatocyte senescence. Transfection of insulin-like growth factor (IGF)-1 adenovirus vector into primary hepatocytes had overexpressed IGF-1, and had alleviated the number of SA-ß-Gal-positive cells. The expression of p53 and progerin was down-regulated in the nucleus, while the expression of p53 was up-regulated in the cytoplasm. The co-precipitation and co-localization of p53 and progerin was decreased in the nuclear region of hepatocytes. IGF-1 overexpression can inhibit intranuclear p53 translocation, alleviate the interaction between p53-progerin, and alleviate hepatocyte senescence.

Forensic Progress on Death Following Carotid Sinus Inhibition.

ABSTRACT: Death after carotid sinus trauma is usually attributed to death from inhibition, a type of sudden death. Currently, the number of incidents is scarce, and related studies are few. Therefore, how to determine the involvement of carotid sinus and determine the role of diseases in the cause of death has always been a difficult point in forensic investigation. This article sorts out the research literature on carotid sinus related death at home and abroad in recent years, systematically reviews the anatomic structure of the carotid sinus nerve, the clinical epidemiology of carotid sinus syndrome, and the research on the death mechanism of carotid sinus injury at home and abroad in recent years, in order to provide references for forensic pathology research and prosecution.

[The mechanism of HDAC6 in paraquat-induced autophagy dysfunction of dopaminergic neurons by mediating aggresome-autophagy-lysosomal pathway].

Objective: To explore the mechanism of HDAC6 mediated aggresome-autophagy-lysosome pathway in paraquat-induced autophagy in dopaminergic neurons. Methods: Human neuroblastoma cell (SH-SY5Y cell) was used as model of dopaminergic neurons in vitro. The cells were treated with terminal concentrations of 0, 25, 50, 100, 200 and 400µmol/L PQ for 24 hours, and the cells were induced by 100 µmol/L PQ for different time (0, 12, 24, 36, 48, 60 and 72 h) . Cell viability was detected by CCK-8 assay. The expression levels of HDAC6, α-syn, Dynein IC1/2, LC3, Beclin1, p62 and Lamp-1 were detected by Western blot. Immunofluorescence double-labeling method was used to observe the expression and localization of HDAC6, α-syn, Dynein IC1/2, LC3, Lamp-1 and γ-tubulin in cells. Results: CCK-8 assay showed PQ induced cell survival rate decrease in a time and dose dependent manner (R=-0.950、-0.960, P<0.05) .Western blot showed that compared with control group, the protein levels of HDAC6, α-syn, p62 in PQ-exposed group were significantly increased (P<0.05) , but there was a significant decrease in expression level of the ratio of autophagy-related protein LC3 Ⅱ/LC3 Ⅰ, Beclin1, Dynein IC1/2, Lamp-1in PQ-exposed group (P<0.05) . The results of immunofluorescence double-labeling showed that compared with the control group, the fluorescence signals of HDAC6 and α-syn in the PQ-exposed group increased, and the protein expression level increased, while the fluorescence signals of Dynein IC1/2, LC3, and Lamp-1 decreased. The protein expression level is reduced. HDAC6 gradually accumulates from the diffuse shape to the nucleus; Under normal circumstances, α-syn, Dynein IC1/2, γ-tubulin, LC3, and Lamp-1 are mainly distributed in the cytoplasm. After PQ is infected, they gather in the nucleus and co-localize with HDAC6 in the area around the nucleus. Conclusion: PQ may induce abnormal aggregation of α-syn by inducing HDAC6-mediated aggresome-autophagy-lysosomal pathway disorder.

[Extraction and Separation of Sinapine from Rapeseed Cake and the Mode of Action of Melanin Production Inhibition].

Brassica campestris L. is the important oil-bearing crop in China. Rapeseed cake is the main byproduct of rapeseed oil extraction. As the main active ingredient in rapeseed cake, sinapine has several important biological activities. Therefore, the inhibitory activity of sinapine on tyrosinase in vitro and its free radical-scavenging rate were determined. Tyrosinase activity in A-375 human melanocytes was also investigated and the effects of sinapine on the melanin content and its antioxidant effects on melanin biosynthesis were studied. The results showed that sinapine had significant antioxidant activity. Sinapine significantly inhibited A-375 human melanocytes in a dose-dependent manner. Sinapine inhibited melanin synthesis in A-375 cells by downregulating the mRNA and protein expression of TRP-1, TRP-2, and MITF factors. The results showed that rapeseed cake sinapine inhibited melanin production and could be used as a potential active ingredient in the development of whitening agents.

[Semiquantitative parameters of 18F-FDG PET/CT, gene mutation states of epidermal growth factor receptor and anaplastic lymphoma kinase in prognosis evaluation of patients with lung adenocarcinoma].

OBJECTIVE: To explore the valuable predictors for evaluating progression-free survival (PFS) in patients with lung adenocarcinoma, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from 18F-FDG PET/CT, combining with the gene mutation states of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and other clinical characteristics. METHODS: Data of 84 lung adenocarcinoma patients pre-treated, who underwent 18F-FDG PET/CT scans, EGFR gene mutations test, ALK rearrangement assay and other relative tests, were retrospectively collected. Then a series of clinical parameters including EGFR/ALK mutation status and SUV-derived features [maximum standardized uptake value (SUVmax), average of standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were evaluated. Best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Survival analysis was performed using Cox proportional hazards model to determine the prognostic markers for progression-free survival (PFS). Survival curves were obtained through Log-rank test and Kaplan-Meier curve. RESULTS: The median follow-up period was 31 months (24 to 58 months). It was found that SUVmax (≥3.01), SUVmean (≥2.25), MTV (≥25.41 cm3), and TLG (≥55.02) of the primary tumors were significantly associated with PFS in univariate Cox proportional hazards regression. Then regardless of age, gender, co-morbidity, EGFR/ALK mutation status, and treatment program, TLG (≥ 55.02, HR=4.965, 95%CI: 1.360-18.133), TNM stage (Ⅲ/Ⅳ, HR=7.811, 95%CI: 2.977-20.489), pro-gastrin releasing peptide (proGRP) (≥45.65 ng/L, HR=4.070, 95%CI: 1.442-11.487), tissue polypeptide antigen (TPA) (≥68.20 U/L, HR=6.996, 95%CI: 1.458-33.574), alkaline phosphatase (ALP) (≥82.50 IU/L, HR=4.160, 95%CI: 1.416-12.219) and ratio of activated partial thromboplastin time (aPTTR) (≥1.16: HR=4.58, 95%CI: 1.913-10.946) showed the independently relevant to PFS through multivariate Cox proportional hazards analysis. The EGFR mutant (P=0.343) and ALK rearrangement (P=0.608) were not significant either in survival analysis. CONCLUSION: High SUV-derived parameters (SUVmax, SUVmean, MTV and TLG) might provide prognostic value to some extent. Especially, TLG, and other clinical features [TNM stage, proGRP, TPA, ALP, and aPTTR] could be independently and significantly associated with PFS of lung adenocarcinoma patients. However, EGFR/ALK gene status could not be effectively relevant to PFS in lung adenocarcinoma patients.

[Study on the salt intake of Jiaodong residents after the salt reduction intervention program and its correlation with blood pressure].

In 2016, the median of 24-hour urinary sodium, sodium-to-potassium ratio, and sodium intake per capita of residents in Jiaodong area of Shandong Province were 161.7 (IQR:120.5, 218.9) mmol/d, 3.4 (IQR: 2.4, 5.0) and 9.5 (IQR:7.1, 12.8) g/d, all were lower than that of 2011[193.3(IQR:149.2,243.3)mmol/d, 4.5(IQR:3.3,5.9), 11.3(IQR:8.7, 14.2)g/d] (P<0.05); the median of 24-hour urinary potassium was 47.2 (IQR:34.4, 66.5) mmol/d, higher than that of 2011[42.9(IQR:33.6,56.0)] (P<0.05); the proportion of salt intake per capita per day exceeding 5 g (89.9%) was lower than that in 2011 (90.0%). The results of the generalized linear regression model showed that the 24-hour urinary sodium was positively correlated with systolic and diastolic blood pressure [ß values were 0.04 (95%CI: 0.00, 0.07), 0.03 (95%CI 0.01, 0.05), respectively], and the sodium-to-potassium ratio was positively correlated with diastolic blood pressure [ß(95%CI): 0.78 (0.09, 1.47)].

[The association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age among neonatal twins in Shaanxi Province].

Objective: To explore the association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age (SGA) among neonatal twins in Shaanxi Province. Methods: From July to December 2013, a total of 30 027 childbearing aged women, who were pregnant from January 2010 to November 2013 and had definite outcomes, were selected from 30 districts (counties) of Shaanxi Province by using the multi-stage random sampling method. The questionnaires with a face-to-face survey method were used to retrospectively collect demographic information, pregnancy history, lifestyle during pregnancy, disease history, nutritional supplements, and health care during pregnancy. Information on the gestational age and birth weight of the newborn were obtained by consulting the medical certificate of birth and were registered as twin A and twin B by birth order. Finally, 356 childbearing aged women and their twin babies with complete data were included in the analysis. A generalized estimation equation model was used to analyze the association between the frequency of prenatal care and the risk of SGA among neonatal twins. Results: The age of childbearing aged women was (27.44±4.68) years old, of which 79.49% (283 women) were rural residents and 44.38% (158 women) had seven or more times prenatal care. The gestational age and birth weight were (37.64±2.51) weeks and (2 510±497) g, respectively. The prevalence of SGA was 51.40% (183/356) for twin A and 53.37% (190/356) for twin B, respectively. The prevalence of SGA was 44.30% (70/158) for twin A with seven or more times prenatal care and 42.41% (67/158) for twin B with seven or more times prenatal care, which was lower than that for twins with less than seven times prenatal care, respectively [57.07% (113/198) and 62.12% (123/198)] (P values were 0.017 and <0.001). The results of generalized estimation equation model suggested that compared to those with less than seven times prenatal care, after adjusting for parity, birth order, place of residence, maternal age, occupation, education, family wealth index, passive smoking, pregnancy-induced hypertension syndrome, folic acid, and iron supplement during perinatal period, and gender of the newborn, the OR (95%CI) of risk of SGA among childbearing aged women with seven or more times prenatal care was 0.60 (0.40-0.91). Conclusion: Seven or more times prenatal care could reduce the risk of SGA among neonatal twins in Shanxi Province.

[Protective effects of taurine on neurons and microglia in Parkinson's disease-like mouse model induced by paraquat].

Objective: To investigate the protective effect of taurine (Tau) on hippocampus, substantia nigra neurons and microglia in paraquat (PQ) -induced Pakinson's disease-like mice. Methods: In April 2019, the specific pathogen free (SPF) C57BL/6 mice (n=36) were randomly divided into control group (NaCl) , Tau control group (150 mg/kg) , PQ exposure group (10 mg/kg PQ group, 15 mg/kg PQ group) , Tau intervention group (Tau+10 mg/kg PQ group, Tau+15 mg/kg PQ group) , respectively. Tau was used in 1 h before PQ administration for consecutive 6 weeks (twice per week) . General and neurobehavioral tests (Traction test, Open field test, Forced Swimming test, Tail suspension test, High plus maze and Object recognition test) were performed to test motor and cognitive function. After neuroethology detection, mice were euthanized and brains were collected. Nissl staining was used to detect the changes of the number and morphology of Nissl bodies in hippocampus and substantia nigra neurons of mice. Immunohistochemistry (IHC) was used to test the levels of neuron marker neuronal nuclei antigen (NeuN) , substantia nigra dopaminergic neuron marker tyrosine hydroxylase (TH) , α-synuclein (α-syn) , microglia markers ionized calcium bindingadaptor molecule-1 (Iba-1) , inducible nitric oxide synthase (iNOS) and interleukin-1ß (IL-1ß) in mice substantia nigra. The coexpression of Iba-1 and TH double-labeling, α-syn and TH double-labeling in mice substantia nigra were measured by immunofluorescence double staining. Results: General behavioral changes such as slow reaction and reduced action occurred in mice of PQ group. Compared with the control group, the scores of Traction test, and the time ratio of new object recognition in the PQ group decreased (P<0.05) , the fixed time of Swimming test and Tail suspension test increased (P<0.05) , the horizontal crawl number and vertical times of Open field test and the ratio of open arm residence time of High plus maze in the 15 mg/kg PQ group decreased (P<0.05) . Compared with the PQ group, the same dose of Tau+PQ group showed increased scores in Traction test (P<0.05) and decreased fixed time of Swimming test and Tail suspension test (P<0.05) . Compared with the 15 mg/kg PQ group, the horizontal crawl number of Open field test and the time ratio of new object recognition increased in the Tau+15 mg/kg PQ group (P<0.05) . Compared with the control group, the PQ group showed a decrease in the number of Nissl body in the hippocampus and substantia nigra (P<0.05) , a decrease in the number of NeuN and TH positive cells in the substantia nigra (P<0.05) , with a large number of α-syn deposition, Iba-1 activation of microglia cells, and an increase in the expression of inflammatory factors (IL-1ß, iNOS) in the hippocampus and substantia nigra (P<0.05) . Compared with the PQ group, the same dose of Tau+PQ group showed the number of Nissl in the hippocampus and substantia nigra was significantly increased (P<0.05) , the number of NeuN and TH positive cells in the substantia nigra was significantly increased (P<0.05) , the expression levels of α-syn, Iba-1 and inflammatory factors (IL-1ß, iNOS) in the substantia nigra were significantly decreased (P<0.05) . Conclusion: Tau could protect PQ-induced degeneration of substantia nigra dopaminergic neurons and hippocampal neuron loss by inhibiting the activation of microglia cells and release of inflammatory factors, and effectively improve the neurobehavioral and brain histopathological changes of PQ-induced PD-like mice.