Discovery of betulinic acid derivatives as gut-restricted TGR5 agonists: Balancing the potency and physicochemical properties.

The pleiotropic effects of TGR5 make it an appealing target for intervention of metabolic and inflammatory disorders, but systemic activation of TGR5 faces challenges of on-target side effects, especially gallbladder filling. Gut-restricted agonists were proved to be sufficient to circumvent these side effects, but extremely low systemic exposure may not be effective in activating TGR5 since it is located on the basolateral membrane. Herein, to balance potency and physicochemical properties, a series of gut-restricted TGR5 agonists with diversified kinetophores had been designed and synthesized. Compound 22-Na exhibited significant antidiabetic effect, and showed favorable gallbladder safety after 7 days of oral administration in humanized TGR5H88Y mice, confirming that gut-restricted agonism of TGR5 is a viable strategy to alleviate systemic target-related effects.

Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling.

Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R-induced acute renal dysfunction and largely blunted I/R-induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL-positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro-apoptotic alteration of Bcl2/Bax expression, caspase-3 activation, loss of mitochondrial membrane potential and KATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the KATP channel blocker 5-HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post-I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage-associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL-1α, IL-6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1-mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI-induced AKI.

Ultrastructural Changes of Brain Tissues Surrounding Hematomas after Intracerebral Hemorrhage.

Our knowledge about pathophysiology of intracerebral hemorrhage (ICH) mainly originates from preclinical models of ICH. In this study, cerebral ultrastructure surrounding hematoma and its correlation with clinical severity were investigated in ICH patients. Thirty patients with basal ganglia hemorrhage and 6 control subjects were enrolled. Surgical evacuation was performed for patients with a blood loss >30 ml. Stroke severity was assessed using the Glasgow Coma Scale (GCS) and the National Institute of Health Stroke Scale (NIHSS). Transmission electron microscopy (TEM) was used to evaluate the ultrastructural characteristics of tissue specimens. Neural cells surrounding the hematomas showed evidence of cell swelling and necrosis. Decreased numbers of organelles and mitochondrial cristae were accompanied by cytoplasmic vacuolization, nuclear membrane invagination and breakdown, and intranuclear chromatic agglutination. These changes resulted in disintegration together with malacia, disappearance of the nucleus and nucleolus, and karyopyknosis. More serious ultrastructural damage was seen in patients with greater NIHSS scores, lower GCS scores, and greater bleeding volumes (p < 0.001). These findings suggest that neural cells undergo unfavorable ultrastructural changes that are responsible for dysfunction after ICH.

Effects of nicotine on proliferation and survival in human umbilical cord mesenchymal stem cells.

Cigarette smoking is known to have negative effects on tissue repair and healing. The aim of this study is to investigate the effects of nicotine in human umbilical cord mesenchymal stem cells (MSCs). After nicotine treatment, MSCs became pyknotic, vacuoles appeared in the cytoplasm and nucleus, and the nuclear boundary became fuzzy as observed using atomic force microscopy. Cell proliferation was inhibited in a dose-dependent manner (P < 0.05 for all concentrations). The proportion of apoptotic MSCs was significantly increased in a dose-dependent manner. The mitochondrial membrane potential was significantly decreased (P < 0.05). Nicotine-treated MSCs had a significantly higher G0/G1 ratio (P < 0.05). Peptide mass fingerprinting identified 27 proteins that were differentially expressed between MSCs with and without nicotine treatment. These nicotine exerted toxic effects on MSCs are likely related, at least in part, to the altered expression of multiple proteins that are essential to the health and proliferation of these cells.

[Detection of Angiostrongylus cantonensis larvae with a high resolution melt PCR assay].

OBJECTIVE: To develop a detection method of the third-stage larvae of Angiostrongylus cantonensis by real-time PCR and high-resolution melt curve analysis. METHODS: A pair of specific primers was designed based on the internal transcribed spacer 1 (ITS1) region of the nuclear ribosomal DNA of A. cantonensis. The third-stage larvae of A. cantonensis were detected by real-time PCR and high-resolution melt curve analysis. The specificity of the method was analyzed by testing DNAs of A. cantonensis, Clonorchis sinensis, and Gnathostoma spinigerum. The genomic DNA were extracted from 1 to 10 third-stage larvae of A. cantonensis, respectively, and used to identify the sensitivity of the method. RESULTS: This method could specifically detect A. cantonensis and the detection limit reached to one larva. No amplification curve and melt curve were found in C. sinensis and G. spinigerum. CONCLUSION: Real-time PCR and high-resolution melt curve analysis show good specificity and sensitivity for detecting the third-stage larvae of A. cantonensis.

Alkaloid uptake pathways in renal tubular epithelial cells from different processed products of Phellodendri chinensis Cortex.

This study aimed to investigate the absorption of alkaloids from Phellodendri chinensis Cortex (PC) by human renal tubular epithelial cells (HK-2). Cellular uptake and affinity ultrafiltration assays were employed to determine the alkaloid uptake pathway in HK-2 cells. Stemming from the hypothesis that salt-water processed PC introduces these alkaloids into the kidney at a cellular level, this research focused on different processed products of PC that are tailored for renal targeting. Utilizing the UPLC-QqQ-MS method, we quantified variations in the uptake capacity of phellodendrine, magnoflorine, jatrorrhizine, berberrubine, and berberine from raw Phellodendri chinensis Cortex (RPC), salt-water processed Phellodendri chinensis Cortex (SPC), and wine processed Phellodendri chinensis Cortex (WPC) in HK-2 cells. This study also tracked the concentration changes of these five alkaloids in HK-2 cells during the administration phase. Further, we evaluated the influence of two inhibitors on the absorption of these five alkaloids from PC and its processed products into HK-2 cells: the organic anion transporters (OATs) inhibitor-probenecid (PRO), and the organic cationic transporters (OCTs) inhibitor-tetraethylammonium chloride (TEAC). A pivotal component of this research was an investigation into the effects of PC and its processed products on the expression levels of OCT2, OAT1, and OAT3 proteins in HK-2 cells, facilitated by Western blot analysis. Finally, we appraised the binding affinity of PC's alkaloids to OCT2, OAT1, and OAT3 proteins using an ultrafiltration centrifugation technique. The uptake of different processed products of PC by HK-2 cells showed the following trend: SPC group > RPC group > WPC group. When considering inhibitor uptake in HK-2 cells, the group treated with PRO (an OATs inhibitor) demonstrated a higher uptake than the group treated with TEAC (an OCTs inhibitor). It was observed that different processed products of PC elevated the expression of OCT2 and OAT1 proteins in HK-2 cells. Specifically, both the SPC and berberrubine groups displayed enhanced expression of these proteins, with a marked increase noted for OCT2. Through affinity ultrafiltration assays, it was determined that the binding affinity of alkaloids from different processed products of PC to OCT2 and OAT1 significantly exceeded that to OAT3. These results indicate that PC-derived alkaloids are absorbed by HK-2 cells, predominantly through transport mechanisms mediated by OCT2 and OAT1, with OCT2 serving as the dominant transporter. The higher intake of alkaloids in SPC group can likely be linked to the amplified activity of kidney uptake transporters.

Enhanced expression of MYF5 and MYOD1 in fibroblast cells via the forced expression of bos taurus MYF5.

The formation of vertebrate skeletal muscles widely thought to be under the control of hierarchy of regulatory genes. MYF5 is one of the myogenic determination gene expressed in the developing mouse dermomyotome which control skeletal muscle differentiation. In the current work, we had obtained the cDNA sequence including the full coding region of the bos taurus myogenic factor MYF5 by reverse transcription polymerase chain reaction. Furthermore, we examined whether fibroblast cell derived from mouse and bos taurus can be transduced using plasmid vectors carrying bos taurus MYF5. Bos taurus MYF5 activates MYF5 and MYOD1 expression after 1 day culture. The concerted upregulation of the myogenic regulatory factors enhanced myosin (skeletal fast) expression. These observation show that MYF5 is essential for myogenic differentiation and provides candidates for regulation bos taurus skeletal muscle development.

Discovery of Betulinic Acid Derivatives as Potent Intestinal Farnesoid X Receptor Antagonists to Ameliorate Nonalcoholic Steatohepatitis.

Farnesoid X receptor (FXR) has emerged as a promising therapeutic target for nonalcoholic steatohepatitis (NASH) because of its tightly interwoven relationship with bile acid homeostasis, inflammation, fibrosis, and glucose and lipid metabolism. Evidence showed that intestinal FXR antagonism exhibited remarkable metabolic improvements in mice. Herein, we developed a series of betulinic acid derivatives as potent intestinal FXR antagonists, and F6 was identified as the most potent one with an IC50 at 2.1 µM. F6 selectively inhibited intestinal FXR signaling and ameliorated the hepatic steatosis, inflammation, and fibrosis in Gubra-amylin NASH (GAN) and high-fat with methionine and choline deficiency (HFMCD) diet-induced NASH models. The beneficial effects were achieved by direct antagonism of intestinal FXR and feedback activation of hepatic FXR, thereby decreasing ceramides and repressing inflammasome activation in the liver. Collectively, our work substantially supports F6 as a promising drug candidate against NASH and demonstrates that antagonism of intestinal FXR signaling is a practical strategy for treating metabolic diseases.

[Analysis of survival motor neuron gene conversion in patients with spinal muscular atrophy].

OBJECTIVE: To investigate the type and frequency of gene conversion from SMN1 to SMN2 in Chinese patients affected with spinal muscular atrophy (SMA), and to explore the relationship between gene conversion and clinical phenotype. METHODS: Non-homozygous deletion of SMN1 gene exon 8 was screened among 417 patients with SMN1 exon 7 homozygous deletions. To analyze and verify the types of gene conversion, genomic DNA sequencing, multiplex ligation-dependent probe amplification (MLPA), and gene subcloning and sequencing were carried out. RESULTS: Thirty-one patients (7.4% of all) with non-homozygous deletions of SMN1 exon 8 were detected. Through series of experiments, the fusion genes SMN1/SMN2 in all cases were delineated. Five types of gene conversions were identified, which included SMN2-I7b/SMN1 E8, SMN2-I7a/SMN1 I7b, SMN2-E7/SMN1 I7a, SMN1 I6/SMN2 E7/SMN1 I7a and SMN2-E7/SMN1 I7a/SMN2 I7b. Such conversions were found in the type I-III patients. For 10 patients with type I-III SMA and 3 copies of SMN2 gene produced by conversion, the average survival age was 5 year and 4 months. CONCLUSION: Partial conversions of SMN1 gene have been found among Chinese SMA patients. The type of conversion and frequency seem to be different from those of other races. Gene conversion to some extent may impact on survival time and rate of SMA patients, especially type I SMA.

[Anti-aging effect of transplantation of mouse fetus-derived mesenchymal stem cells].

To determine the role of allogeneil graft of mesenchymal stem cells in mammalian longevity, mesenchymal stem cells were isolated from BALB/c mouse uterine-incision delivery fetus by two successive density gradient centrifugations, and then were purified and amplified by adherent culture. Identified P1 mesenchymal stem cells were injected (i.v.) through vena caudalis into the 15-month-old female BALB/c mice three times. The mice were evaluated with ultrasoundcardiogram, autopsy, score of cardiac, skin, lung, kidney, colon histopathology and serum total superoxide dismutase activity, maleic dialdehyde content, glutathione peroxidase activity. The results showed that after transplantation, the long-term surviving stem cells were found to be located in many organ tissues with in situ Y chromosomal hybridization dyeing. Median life span was increased in these animals after transplantation. Skin, cardiac, lung, kidney and colon pathology development were delayed. The retrogradation of heart function was attenuated, the increase of heart mass index (the mass of heart/the mass of the body), and serum maleic dialdehyde content, the decrease of spleen mass index (the mass of spleen/the mass of the body), serum total superoxide dismutase activity and glutathione peroxidase activity were reduced three months after transplantation (all P<0.05). These results support the idea that longevity can be enhanced by transplantation of mesenchymal stem cells and reinforce the hypothesis of mesenchymal stem cell as antiager.

Growth hormone therapy for children with KBG syndrome: A case report and review of literature.

BACKGROUND: The incidence of short stature in KBG syndrome is relatively high. Data on the therapeutic effects of growth hormone (GH) on children with KBG syndrome accompanied by short stature in the previous literature has not been summarized. CASE SUMMARY: Here we studied a girl with KBG syndrome and collected the data of children with KBG syndrome accompanied by short stature from previous studies before and after GH therapy. The girl was referred to our department because of short stature. Physical examination revealed mild dysmorphic features. The peak GH responses to arginine and clonidine were 6.22 and 5.40 ng/mL, respectively. The level of insulin-like growth factor 1 (IGF-1) was 42.0 ng/mL. Genetic analysis showed a c.2635 dupG (p.Glu879fs) mutation in the ANKRD11 gene. She received GH therapy. During the first year of GH therapy, her height increased by 0.92 standard deviation score (SDS). Her height increased from -1.95 SDS to -0.70 SDS after two years of GH therapy. There were ten children with KBG syndrome accompanied by short stature who received GH therapy in reported cases. Height SDS was improved in nine (9/10) of them. The mean height SDS in five children with KBG syndrome accompanied by short stature increased from -2.72 ± 0.44 to -1.95 ± 0.57 after the first year of GH therapy (P = 0.001). There were no adverse reactions reported after GH treatment. CONCLUSION: GH treatment is effective in our girl and most children with KBG syndrome accompanied by short stature during the first year of therapy.

Elevated GTP Cyclohydrolase I Pathway in Endothelial Progenitor Cells of Overweight Premenopausal Women.

Background/Aims. Sexual differences exist in endothelial progenitor cells (EPCs), and various cardiovascular risk factors are associated with the preservation of endothelial function in premenopausal women. However, it is unclear whether differences in endothelial function and circulating EPCs exist between overweight premenopausal women and age-matched men. Methods. We compared EPC counting and functions in normal-weight and overweight premenopausal women and men, evaluated endothelial function in each group, and detected the expression of the guanosine triphosphate cyclohydrolase I (GTPCH I) pathway. Results. The number of EPCs was lower in the male group than in the female group, regardless of normal-weight or overweight status, and there was no significant difference between the different weight groups among females or males. Endothelial function and EPC migration and proliferation were preserved in overweight premenopausal women compared with overweight men as were nitric oxide (NO) levels in plasma and secreted by EPCs. Endothelial function, the circulating EPC population, and NO levels were not different between normal-weight and overweight premenopausal women. Flow-mediated dilatation was significantly correlated with EPC function, plasma NO levels, and EPC-secreted NO. Conclusions. This investigation provides the first evidence for sex-based differences in EPC activity and endothelial function in overweight middle-aged individuals; these differences are associated with alterations in NO production and may partly occur through downregulation of the GTPCH I pathway. The present results provide new insights into the mechanism underlying the preserved endothelial function in overweight premenopausal women and may uncover a potential therapeutic target for endothelial repair in overweight population.

Pd-Catalyzed decarboxylative cross-coupling reactions of epoxides with α,ß-unsaturated carboxylic acids.

A Pd-catalyzed decarboxylative cross-coupling of α,ß-unsaturated carboxylic acids with cyclic and acyclic epoxides has been developed. Both ß-monosubstituted and ß-disubstituted unsaturated carboxylic acids, as well as conjugated diene unsaturated carboxylic acids are suitable reaction substrates. Substituted homoallylic alcohols were obtained in moderate to good yields. The product was obtained as a mixture of diastereomers favoring the anti diastereomer of the cyclic epoxides. This work provides a method for the modification of complex organic molecules containing α,ß-unsaturated carboxylic acids.

Trisubstituted olefin synthesis via Ni-catalyzed hydroalkylation of internal alkynes with non-activated alkyl halides.

The stereoselective synthesis of tri-substituted alkenes is challenging. Herein, we report a Ni-catalyzed regio- and stereo-selective hydroalkylation of internal alkynes with non-activated alkyl halides. This method does not use any sensitive organometallic reagents and shows good functional group compatibility, which enables the efficient synthesis of many tri-substituted olefins from readily available coupling partners. It also provides a straightforward method for the modification of bioactive organic molecules.

Development and validation of immortalized bovine mammary epithelial cell line as an in vitro model for the study of mammary gland functions.

This study aimed to develop a bovine mammary epithelial (BME) cell line model, which provides a possibility to determine functional properties of the bovine mammary gland. The primary cell culture was derived from bovine mammary gland tissues and processed enzymatically to obtain cell colonies with epithelial-like morphology. The cultures of BME cells were purified and optimally cultured at 37 °C in DMEM/F12 medium supplemented with 10% fetal bovine serum. The BME cells were identified as epithelial cell line by the evaluating the expression of keratin-18 using immunofluorescence staining. A novel gene expression system strongly enhances the expression of telomerase, has been used to immortalize BME cell line termed hTBME cell line. Interestingly, telomerase remained active even after over 60 passages of hTBME cell line, required for immortalization of BME cells. In addition, the hTBME cell line was continuously subcultured with a spontaneous epithelial-like morphology, with a great proliferation activity, and without evidence of apoptotic and necrotic effects. Further characterization showed that hTBME cell line can be continuously propagated in culture with constant chromosomal features and without tumorigenic properties. Finally, established hTBME cell line was evaluated for mammary gland specific functions. Our results demonstrated that the hTBME cell line was able to retain functional-morphological structure, and functional differentiation by expression of beta (ß)-casein as in the bovine mammary gland in vivo. Taken together, our findings suggest that the established hTBME cell line can serve as a valuable tool for the study of bovine mammary gland functions.

[Impact of tillage and nutrient management practices on the spring weed community in a winter wheat-summer maize rotation farmland]. / è€•ä½œå’Œå »åˆ†ç®¡ç†æ–¹å¼å¯¹å†¬å°éº¦-夏玉米轮作农田春季杂草群落的影响.

Conservation tillage and the weed diversity are two hot issues in the modern ecological agriculture. Although it is known that the diversity of weed would increase slightly in the farmland under conservation tillage, the interaction effects between the tillage and the nutrient management on the weed community are not clear. In this study, one wheat-maize rotation field located in Ji'nan, Shandong Province, was selected as the studying site. Different tillage methods (no-tillage, deep subsoiling, rotary tillage, deep tillage) and different nutrient managements (farmers routine, 480 kg N hm-2 per year; high production and efficiency, 360 kg N hm-2 per year; optimal management, 300 kg N hm-2 per year) were carried out for 3 years. The characteristics of the spring weed communities under different managements were investigated and compared. The results showed that there were 15 species in the spring weed communities in the test filed and Digitaria sanguinalis and Echinochloa crusgalli were the dominant species. The plots under no-tillage or deep subsoiling had higher weed densities compared with those under the deep tillage or rotary tillage. In terms of the effect of tillage on the weed community diversity, both species richness index and species evenness index were lowest but the community dominance index was highest in the plots under deep tillage. In terms of the effect of the nutrient management, with the increase of fertilizer application, both species richness and evenness index increased under the different tillage methods. The community dominance increased with the increasing fertilizer application under deep tillage or rotary tillage and vice versa under no-tillage, deep subsoiling. In terms of weed biomass, the plots under no-tillage or deep subsoiling had significantly higher weed biomass than those under the other two tillage methods. The plots under routine nutrient management had higher weed biomass than those under the other two nutrient managements. Among all these treatments, the plots under the combination treatment of no-tillage and routine nutrient management had the highest weed biomass. According to these results, it was implied that no-tillage and fertilization would improve species richness index, species evenness index, and the productivity of spring weed community in the wheat-maize farmland.

Inhibition of Adipogenesis Is Involved in the Protective Effects of 1,25-Dihydroxy Vitamin D3 on the Radiation-Injured Bone Marrow Microenvironment in Mice.

To explore the protective effects of 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3) on the bone marrow microenvironment in mice after irradiation and the underlying molecular mechanisms, a total of 150 7-wk-old male BALB/c mice were randomly divided into a normal group, an irradiation (IR) group and an irradiation+1,25-(OH)2D3 (IR+VD3) group. The mice in the IR+VD3 group were treated with 6.0 Gy 60Coγ rays, and 1,25-(OH)2D3 (dissolved in DMSO, 2.5 µg/kg) was administered once per day from 2 d before to 8 d after irradiation. Mice in the IR group were treated with the same dose of γ rays and an equal volume of DMSO. Subsequently, the body weights and the numbers of peripheral white blood cells (WBCs) were measured. Histological analysis of femur bone marrow was conducted to determine the proportion of adipose area as well. Finally, the expression of peroxisome proliferator-activated receptor-gamma (PPARγ) in bone marrow was detected by immunohistochemistry. After irradiation, the percentage of adipose area in the bone marrow was significantly increased, and the WBC number and body weight were markedly reduced. Compared with irradiation alone, the co-administration of 1,25-(OH)2D3 with irradiation markedly attenuated radiation-induced adipogenesis in bone marrow, resulted in fewer bone marrow stromal cells expressing PPARγ and enhanced the recovery of body weight and WBCs. These results indicate that 1,25-(OH)2D3 could accelerate the recovery of body weight and WBCs in irradiated mice and protect the bone marrow by inhibiting radiation-induced adipogenesis via the down-regulation of PPARγ expression.

[Effects of dihydroartemisinin on radiosensitivity of Raji cells].

OBJECTIVE: To study the effects of dihydroartemisinin (DHA) on radiation sensitivity of Raji cells, and explore its mechanisms. METHODS: CCK8 was used to determine the effect of DHA on cell viability of Raji cells; apoptosis, intracellular reactive oxygen speies(ROS) and mitochondrial membrane potential of Raji cells were detected by flow cytometry; and the protein expressions of protein kinase B(AKT), phospho-rylated-protein kinase B(p-AKT), Bcl-2 and Bax were determined by Western blot. RESULTS: The cells were randomly divided into four groups:control group, DHA(5µmol/L DHA), irradiation(IR, 4 Gy), IR+DHA group (4 Gy IR+5 µmol/L DHA). Compared with the other three groups, cells in DHA+IR group exhibited lower mitochondrial membrane potential (P<0.01). While the intracellular ROS content and apoptosis rate of Raji cells in DHA+IR group were increased significantly(P<0.01). In addition, compared with the other three groups, there was no significant difference in the expression of AKT, but the phosphorylation of AKT protein were significantly inhibited and the expression of Bcl-2 protein was markedly decreased. However, the expressions of Bax and Cleaved-Caspase-3 protein were markedly increased. CONCLUSIONS: DHA might activate the mitochondrial apoptotic signal via inhibiting phosphoinositide 3-kinase (PI3K/AKT) pathway and increase oxidative stress to enhance the radiosensitivity of Raji cells.

[Following up investigation of forensic psychiatry judicial expert mental testimony].

OBJECTIVE: To study different viewpoints to the conclusion and treatment, And the following up factors concerning social effect after the judgment of forensic psychiatry. METHODS: By letters, calls, visits and by investigation forms made by myself, 208 testimonied cases were followed up separately from judicial organ or other organizations and institutes, individuals testimonied or their family members, victims and their family members. RESULTS: Most testimonied individuals were married man of 30 years old or so whose average education were 4.84 years and testimonied by the public security organs. In criminal cases, violental criminals (129 cases, 83.77%) were much more than non-violental criminals (25 cases, 16.23%) and homicide criminals (44 cases, 28.57%) were most common in the former but civil cases were few. The rate of retstinvony was 2.93%. The testimonied individuals and their family members thought the condemn were appropriate (76.47%) for the people without criminal capacity and thought the condemn were appropriate (41.94%) or not appropriate (41.94%) for the people with criminal capacity. The opinions of the condemn for partial criminal capacity were between the former two cases. And they thought the condemn for 28 cases of non-guilty were appropriate (71.43%) and not appropriate (10.7%). 7 victims were dead. 10 victims were crippled. 10 victims restored to health. In 41 persons testimonied and set free with a verdict of "not guilty", 4 homicided again (4.87%), 2 set on fire (4.87%), 2 stealed (4.87%) and 3 had wrecked behavior (7.31%). CONCLUSION: So it is suggested that the department concerned should keep criminals with mental disorder under control and treatment.

[Response of Human Respiratory Height PM2.5 Variation Characteristics to Meteorological Factors During Winter Haze Days in Beijing].

In order to investigate the influence of meteorological factors on the variation characteristics of PM2.5 in Beijing. According to the survey of PM2.5 mass concentration in height of human respiration, humidity, the direction of the wind, wind speed and temperature. Using the methods of correlation analysis and nonlinear regression analysis, the effects of meteorological factors on the formation and variation of PM2.5 mass concentration in light and moderate air pollution days and heavy pollution were discussed respectively. The results showed that:① On mild to moderate pollution days, if the temperature was low, the daily average wind speed was low, the humidity was high, then the humidity was the decisive influencing factor of PM2.5 mass concentration; if the temperature, wind speed and humidity were all high, then the variation of PM2.5 mass concentration was influenced by the combined action of these three; when the temperature, humidity and wind speed were all low, then the PM2.5 mass concentration was mainly affected by the first two factors. This suggested that changes in the height of the human respiration PM2.5 mass concentrations were extremely sensitive to small changes in meteorological factors; ② During the process of air quality turning from good to heavily polluted, the accumulation of PM2.5 mass concentration was mainly due to the weak air turbulence, coupled with the high humidity, in addition, the northwest wind and northeast wind were larger during the daytime but the duration was shorter, while the southeast and southwest wind speed at night was lower with longer duration, which was conducive to pollutant accumulation;③ Short-term low amount of snow decreased the temperature and increased the air humidity, which not only could not reduce the PM2.5 mass concentration, but rather increased it by 72%, resulting in the jump phenomenon of particle concentration; ④ When the wind speed reached up to 2.0 m·s-1 and lasted for two hours, the local PM2.5 mass concentrations could be reduced to some extent, but it could not completely change the air quality situation. Only when the wind speed was greater than 3.5 m·s-1 and lasted for more than 4 hours, the fine particulate matter in the air could be quickly diffused and the air quality was changed from heavy pollution to excellent.