Ocular trauma from Lawn mower accidents: Clinical insights, visual outcomes and microbial profiles.

AIMS: To characterize the clinical features of ocular trauma resulting from lawn mower, identify determinants of unfavorable final visual acuity (FVA), and assess the spectrum of microbial in posttraumatic endophthalmitis. METHODS: This retrospective study enrolled patients who experienced ocular trauma due to lawn mower at Zhongshan Ophthalmic Center from January 2013 to August 2021. Demographics, clinical features, isolated microorganisms, risk factors influencing reduced visual acuity, treatment regimens, and utilization of eyewear were collected. RESULTS: The study included 140 participants (140 eyes) (49.47 ± 12.03 years, 95% male). The predominant injury manifestations were penetrating globe injuries (75.7%) and intraocular foreign bodies (51.4%). Endophthalmitis occurred in 35 cases (25%) and Bacillus cereus (23.5%) was the primary pathogen, followed by Staphylococcus epidermidis (11.8%) and Streptococcus species (11.8%). Following the initial assessment, where 77.9% of patients had initial visual acuity (IVA) at grade IV (ranging from light perception to 4/200) and only 0.7% attained grade I (better than 20/40), post-treatment results revealed that 5.7% achieved FVA at grade I, with a concurrent decrease in patients with grade IV vision to 64.3%. Multivariate logistic regression revealed that injury protection (p < 0.001, OR = 0.237, 95% CI = 0.126-0.446), IVA (p = 0.001, OR = 4.102, 95% CI = 1.730-9.729), and retinal detachment (p = 0.042, OR = 8.105, 95% CI = 1.075-61.111) were significant independent risk factors impacting FVA. CONCLUSION: Lawn mower often cause severe ocular injuries, with high-velocity metal foreign bodies that can lead to infections, most commonly caused by Bacillus cereus. Correct use of protective gear, initial vision assessment, and detecting retinal detachment are crucial for visual prognosis.

The intestinal absorption properties of flavonoids in Hippophaë rhamnoides extracts by an in situ single-pass intestinal perfusion model.

The purpose of this study was to investigate the absorption properties of isorhamnetin (IS), quercetin (QU), and kaempferol (KA) in total flavones of Hippophaë rhamnoides L. (TFH) by an in situ single-pass intestinal perfusion model. The results indicated that IS, QU, and KA in TFH were absorbed site-dependently, and both enterohepatic circulation and intestinal flora could participate in their absorption processes. The absorption mechanisms of IS, QU, and KA in TFH were involved in both passive diffusion and active transport, and the mediation of efflux transporter multidrug resistance-associated proteins (MRPs) should not be neglected.

A novel strategy for pharmaceutical cocrystal generation without knowledge of stoichiometric ratio: myricetin cocrystals and a ternary phase diagram.

PURPOSE: To develop a streamlined strategy for pharmaceutical cocrystal preparation without knowledge of the stoichiometric ratio by preparing and characterizing the cocrystals of myricetin (MYR) with four cocrystal coformers (CCF). METHODS: An approach based on the phase solubility diagram (PSD) was used for MYR cocrystals preparation and the solid-state properties were characterized by differential scanning calorimetry (DSC), fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The ternary phase diagram (TPD) was constructed by combining the PSD and nuclear magnetic resonance (NMR) data. After that, the TPD was verified by traditional methods. The dissolution of MYR in the four cocrystals and pure MYR within three different media were also evaluated. RESULTS: A simple research method for MYR cocrystal preparation was obtained as follows: first, the PSD of MYR and CCF was constructed and analyzed; second, by transforming the curve in the PSD to a TPD, a region of pure cocrystals formation was exhibited, and then MYR cocrystals were prepared and identified by DSC, FT-IR, PXRD, and SEM; third, with the composition of the prepared cocrystal from NMR, the TPD of the MYR-CCF-Solvent system was constructed. The powder dissolution data showed that the solubility and dissolution rate of MYR was significantly enhanced by the cocrystals. CONCLUSIONS: A novel strategy for pharmaceutical cocrystals preparation without knowledge of the stoichiometric ratio based on the TPD was established and MYR cocrystals were successfully prepared. The present study provides a systematic approach for pharmaceutical cocrystal generation, which benefits the development and application of cocrystal technology in drug delivery.

Factors affecting the severity and prognosis of visual damage in inhalational methanol poisoning.

Background/Aim: Inhalational methanol poisoning could cause severe damage to visual function. This study analyzed the prognosis of the correlation between the visual function and the relevant risk factors. Methods: In this retrospective study, 14 patients had confirmed inhalational methanol poisoning, resulting in visual impairment in both eyes. The following tests were performed: laboratory tests, best corrected visual acuity (BCVA), intraocular pressure, slit lamp, fundus photography, visual field (VF), pattern visual evoked potential (P-VEP), flash electroretinogram (F-ERG), optical coherence tomography (OCT), and orbital or cranial magnetic resonance imaging (MRI). Results: With active treatment, visual function improved to varying degrees in all 14 cases (28 eyes) in this study. The BCVA of 21 eyes declined to no light perception at the onset; 16 eyes showed different degrees of improvement after treatment, with the final BCVA (LogMar) mainly ranging from 2 to 3, and vision acuity stabilized after the 5th month. The VF pattern in the acute phase was mostly blind. Other VF patterns included the central visual island, large paracentral scotomas, hemipleural VF defects, and the temporal visual island. Retinal nerve fiber layer (RNFL) thickening was observed commonly in the acute phase (146.8 ± 33.2 µm), which subsided in the 1st month, showed dramatic thinning at the 3rd month, and then stabilized in the 5th month after onset. MRI showed that the main sites involved were optic nerve impairment, the optic disk, and retrobulbar segments. The basal ganglia region was the site most involved in the central nervous system (CNS). Conclusion: Inhalational methanol poisoning could lead to severe impairment of visual function, and the prognosis of visual acuity (VA) was highly relevant to the risk factors of duration of toxic exposure, delayed admission, and degree of acidosis.

Sleep disturbance and quality of life among university freshmen in Qinghai-Tibet Plateau of China.

Purpose: University freshmen are particularly vulnerable as they are undergoing the transition from high school to university with a range of changes. Sleep problems among this group in the Qinghai-Tibet Plateau of China were barely studied. This study aimed to explore sleep disturbance, and its association with quality of life (QoL) and demographic and clinical characteristics among university freshmen in Qinghai-Tibet Plateau, China. Methods: A multistage stratified cluster random sampling method was performed to recruit student participants with a structured questionnaire to collect sociodemographic and clinical characteristics, and lifestyle behaviors. Sleep disturbance including three aspects of sleep disturbance (i.e., difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA)) was assessed using standardized measurement. Multiple logistic regression models were applied to analyze the data. Results: Among included 2,769 freshmen, the prevalence of sleep disturbance was 14.8% (95% CI: 14.2-15.5%), and corresponding prevalence of DIS, DMS, and EMA was 8.2% (95% CI: 7.7-8.7%), 8.3% (95% CI: 7.8-8.8%), and 4.2% (95% CI: 3.8-4.6%), respectively. Freshmen with sleeping disturbance had significantly lower QoL in physical [F (1, 2769) = 60.23, p < 0.001], psychological [F (1, 2769) = 46.18, p < 0.001], social [F (1, 2769) = 23.04, p < 0.001], and environment [F (1, 2769) = 6.07, p = 0.01] domains. Multiple logistic regression analyses revealed that having breakfast five times a week or less (less than three times, OR = 1.79, 95% CI: 1.34-2.40; 3-5 times, OR = 1.40, 95% CI: 1.09-1.79), self-perceived severe Internet dependence (OR = 1.71, 95% CI: 1.11-2.65), self-perceived poor health status (OR = 3.44, 95% CI: 2.06-5.74), high academic stress (OR = 1.42, 95% CI: 1.13-1.78), poor relationship with classmates (OR = 3.44, 95% CI: 1.53-7.71), and severe ADHD symptoms (OR = 1.08, 95% CI: 1.05-1.12) were positively associated with sleeping disturbance. Conclusion: Sleep disturbance was common among freshmen and is associated with poorer QoL. Prevention and intervention strategies should be developed and implemented, especially among the vulnerable university freshman groups.

[An analysis of subhealth status based on partial least squares].

OBJECTIVE: To explore the discrimination model of subhealth with statistical method of partial least squares (PLS). METHODS: This study was based on the Subhealth State Rating Scale (SHSRS). A total of 88 subhealth subjects (scoring less than 85 in SHSRS) and 64 healthy people (scoring over 85 in SHSRS) were enrolled randomly. Information regarding the clinical symptoms was screened by stepwise regression as independent variables. Mathematical models were established by leave-one-out in PLS program for subhealth recognition before and after stepwise regression respectively. Accuracy rates were observed and compared by using the Visual Basic 6.0. RESULTS: The practical accuracy rate of PLS models in subhealth recognition was 89.47%, and increased to 92.10% after stepwise regression for variables. CONCLUSION: PLS has certain reference value in establishing subhealth discrimination models. It can also play an important part in item selection of the scale.

Treatment With Melatonin After Corneal Graft Attenuates Rejection.

Background: Immunologic graft rejection is the main complication of corneal transplants. This study aimed to investigate the effect of melatonin (MT) on the rejection of corneal transplantation. Methods: Corneal allografts were performed by grafting corneas from BALB/C mice to C57BL/6 hosts. MT (50 mg/kg) was intraperitoneally injected into the hosts every day from the day of transplantation. The survival of grafts was observed by slit lamp biomicroscopy, and inflammatory cell infiltration was detected by hematoxylin and eosin staining and immunohistochemistry. The balance of Teff and Treg immune cells in draining lymph nodes (DLNs) was detected by flow cytometry. The levels of cytokines related to the grafts and DLNs were detected using real-time fluorescence quantitative PCR. Additionally, we used the mouse macrophage line RAW264.7 to study the effect of MT on the activation of NLRP3 inflammatory body. Results: MT treatment improved the graft survival rate, reduced inflammatory cell infiltration in the graft, decreased the percentage of Th1/Th17 cells in the DLNs, and increased the percentage of Treg cells. Melatonin inhibited the activation of the NLRP3 inflammasome, thereby reducing the expression of IL-1ß and other related proinflammatory cytokines such as MCP-1, MIP-1, NLRP3, ASC, TNF-a and VEGF-A (all p < 0.05). Conclusion: Our study demonstrates that MT promotes the survival of mouse corneal grafts by inhibiting NLRP3-mediated immune regulation, reducing immune cell activation and cell migration, and inhibiting the production of inflammatory-related cytokines. Treatment with MT might provide a potential clinical therapeutic target for corneal transplantation.

Sex differences in the factors associated with sleep duration in university students: A cross-sectional study.

BACKGROUND: Insufficient sleep duration among university students was commonly associated with many detrimental effects. University students experience substantial environmental and psychological changes. Female and male university students may differ in many spheres. However, most research on sleep duration of university students is based on an aggregate sample rather than digging the sex-specific profiles. The objective of this study is to examine potential sex differences in the correlates of sleep duration and explore the underlying mechanism of correlations. METHODS: This is a large-scale university-based mental health survey, which was conducted in university students in Qinghai Province in Northwest China in December 2019. A multi-stage logistic regression was separately fitted by sex to examine the factors associated with short sleep duration in university students. RESULTS: A total of 5,552 university students with an average sleep duration of 6.88 h (SD = 1.04) were included, among which 35.0% of the participants may currently be sleeping less than the optimal duration. Female students (6.84 h, SD = 1.00) slept shorter than males (6.94 h, SD = 1.09). The only parallel between sexes was that both female and male students with 3-5 times weekly breakfast were less likely to have short sleep duration. Adjusting for depressive symptoms in the following step eliminated the association between anxiety symptoms and short sleep duration in the model for female students. Female-specific associated factors with short sleep duration were age, grade, academic pressure, weekly physical exercise, depressive symptoms. Male-specific characteristics were current smoking tobacco cigarette, self-perceived health, duration of daily Internet use. CONCLUSION: Characteristic profiles of sleep duration differed between female and male university students; only a few male-specific factors were identified. Psychological guidance and education courses as well as other interventions to improve university students' sleep and related health should be designed and implemented based on sex differences.

Childhood trauma and suicidal ideation among Chinese university students: the mediating effect of Internet addiction and school bullying victimisation.

AIMS: The factors associated with suicidal ideation among adolescents have been extensively characterised, but the mechanisms underlying the complexities of the relationship between experiences of childhood trauma and suicidal ideation have been less studied. This study examined the direct effect of childhood trauma on suicidal ideation on the one hand and whether school bullying victimisation and Internet addiction mediate the association between childhood trauma and suicidal ideation on the other hand. METHODS: This school-based mental health survey was carried out in Qinghai Province in Northwest China in December 2019. We employed standardised questionnaires to collect sociodemographic and target mental health outcomes. Hierarchical multiple logistic regression and structural equation modelling were performed for the data analyses. RESULTS: This study included 5864 university students. The prevalence of lifetime suicidal ideation and Internet addiction were 34.7% and 21.4%, respectively. Overall, 16.4% and 11.4% of participants reported experiences of childhood trauma and school bullying victimisation, respectively. There were direct effects of childhood trauma, school bullying victimisation and Internet addiction on suicidal ideation. The total effect of childhood trauma on suicidal ideation was 0.201 (p < 0.001). School bullying victimisation and Internet addiction mediated the relationship between childhood trauma and suicidal ideation. Internet addiction played a mediating role between school bullying and suicidal ideation. CONCLUSIONS: Childhood trauma had both direct and indirect effects on suicidal ideation; these effects were mediated by school bullying victimisation and Internet addiction in Chinese university students. Elucidating these relationships will therefore be useful in developing and implementing more targeted interventions and strategies to improve the mental well-being of Chinese university students.

[Sub-health and the "treatment of pro-disease" in Chinese medicine].

The relationship between sub-health and " pro-disease" in Chinese medicine was clarified through analyzing the background of sub-health coming forth and its connotation, as well as the multiple meaning of "pro-disease" in Chinese medicine. The authors offered, thereupon, their clews and methods for treatment of "pro-disease" and intervention on sub-health.

Inhibition of P-Glycoprotein Mediated Efflux in Caco-2 Cells by Phytic Acid.

Phytic acid (IP6) is a natural phosphorylated inositol, which is abundantly present in most cereal grains and seeds. This study investigated the effects of IP6 regulation on P-glycoprotein (P-gp) and its potential mechanisms using in situ and in vitro models. The effective permeability of the typical P-gp substrate rhodamine 123 (R123) in colon was significantly increased from (1.69 ± 0.22) × 10-5 cm/s in the control group to (3.39 ± 0.417) × 10-5 cm/s (p < 0.01) in the 3.5 mM IP6 group. Additionally, IP6 can concentration-dependently decrease the R123 efflux ratio in both Caco-2 and MDCK II-MDR1 cell monolayers and increase intracellular R123 accumulation in Caco-2 cells. Furthermore, IP6 noncompetitively inhibited P-gp by impacting R123 efflux kinetics. The noncompetitive inhibition of P-gp by IP6 was likely due to decreases in P-gp ATPase activity and P-gp molecular conformational changes induced by IP6. In summary, IP6 is a promising P-gp inhibitor candidate.

Urinary Metabolomic Study of Chlorogenic Acid in a Rat Model of Chronic Sleep Deprivation Using Gas Chromatography-Mass Spectrometry.

The urinary metabolomic study based on gas chromatography-mass spectrometry (GC-MS) had been developed to investigate the possible antidepressant mechanism of chlorogenic acid (CGA) in a rat model of sleep deprivation (SD). According to pattern recognition analysis, there was a clear separation among big platform group (BP), sleep deprivation group (SD), and the CGA (model + CGA), and CGA group was much closer to the BP group by showing a tendency of recovering towards BP group. Thirty-six significantly changed metabolites related to antidepressant by CGA were identified and used to explore the potential mechanism. Combined with the result of the classic behavioral tests and biochemical indices, CGA has significant antidepressant effects in a rat model of SD, suggesting that the mechanism of action of CGA might be involved in regulating the abnormal pathway of nicotinate and nicotinamide metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and arginine and proline metabolism. Our results also show that metabolomics analysis based on GC-MS is a useful tool for exploring biomarkers involved in depression and elucidating the potential therapeutic mechanisms of Chinese medicine.

A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota.

Resveratrol and quercetin, widely found in foods and vegetables, are plant polyphenols reported to have a wide range of biological activities. Despite their limited bioavailabilities, both resveratrol and quercetin are known to exhibit anti-inflammation and anti-obesity effects. We hypothesized that gut microbiota may be a potential target for resveratrol and quercetin to prevent the development of obesity. The aim of this research was to confirm whether a combination of quercetin and resveratrol (CQR) could restore the gut microbiota dysbiosis induced by a high-fat diet (HFD). In this study, Wistar rats were divided into three groups: a normal diet (ND) group, a HFD group and a CQR group. The CQR group was treated with a HFD and administered with a combination of quercetin [30 mg per kg body weight (BW) per day] and resveratrol [15 mg per kg body weight (BW) per day] by oral gavage. At the end of 10 weeks, CQR reduced the body weight gain and visceral (epididymal, perirenal) adipose tissue weight. Moreover, CQR also reduced serum lipids, attenuated serum inflammatory markers [interleukin (IL)-6, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1] and reversed serum biochemical parameters (adiponectin, insulin, leptin, etc.). Importantly, our results demonstrated that CQR could modulate the gut microbiota composition. 16S rRNA gene sequencing revealed that CQR had an impact on gut microbiota, decreasing Firmicutes (P < 0.05) and the proportion of Firmicutes to Bacteroidetes (P = 0.052). CQR also significantly inhibited the relative abundance of Desulfovibrionaceae (P < 0.01), Acidaminococcaceae (P < 0.05), Coriobacteriaceae (P < 0.05), Bilophila (P < 0.05), Lachnospiraceae (P < 0.05) and its genus Lachnoclostridium (P < 0.001), which were reported to be potentially related to diet-induced obesity. Moreover, compared with the HFD group, the relative abundance of Bacteroidales_S24-7_group (P < 0.01), Christensenellaceae (P < 0.001), Akkermansia (P < 0.01), Ruminococcaceae (P < 0.01) and its genera Ruminococcaceae_UCG-014 (P < 0.01), and Ruminococcaceae_UCG-005 (P < 0.01), which were reported to have an effect of relieving HFD-induced obesity, was markedly increased in the CQR group. Overall, these results indicated that administration of CQR may have beneficial effects on ameliorating HFD-induced obesity and reducing HFD-induced gut microbiota dysbiosis.

Self-nanoemulsifying drug delivery systems of myricetin: Formulation development, characterization, and in vitro and in vivo evaluation.

Despite various pharmacological effects, myricetin (Myr) shows low oral bioavailability (<10%) due to its poor solubility, which limits its applications. To address this problem, self-nanoemulsifying drug delivery systems (SNEDDS) were developed by investigating the solubility of Myr in various excipients, constructing pseudo-ternary phase diagrams, and optimizing based on droplet size and emulsification efficacy after drug loading. The obtained Myr-SNEDDS were F04 (Capryol 90/Cremophor RH 40/PEG 400 4:3:3), F08 (Capryol 90/CremophorRH40/1,2-propanediol 4:3:3), F13 (Capryol 90/Cremophor EL/Transcutol HP 4:3:3) and F15 (Capryol 90/Cremephor RH 40/Transcutol HP 2:7:1), with droplet sizes less than 200nm. Additional evaluations showed that these Myr-SNEDDS formulations had fast release properties (over 90% in 1min), low cytotoxicity, and improved permeability and solubility compared with the free drug. Consequently, the oral bioavailabilities of Myr were 5.13, 6.33, 4.69 and 2.53-fold for F04, F08, F13 and F15, respectively, relative to Myr alone. The present study demonstrated that SNEDDS is a viable platform for the oral delivery of insoluble drugs such as Myr.

Serum and Brain Metabolomic Variations Reveal Perturbation of Sleep Deprivation on Rats and Ameliorate Effect of Total Ginsenoside Treatment.

Sleep loss or sleep deprivation (SD) refers to shorter sleep than average baseline need, and SD has been a serious problem of modern societies which affects health and well-being. Panax ginseng is a well-known traditional Chinese medicine (TCM). Our previous study has demonstrated that total ginsenosides (GS), the extracts from Panax ginseng, could effectively improve cognition and behavior on SD rats. However, little is known about its metabolomic study. In this study, serum and brain metabolomic method based on gas chromatography coupled with mass spectrometry (GC/MS) was employed to evaluate the efficacy and study the mechanism of GS on a rat model of SD. With pattern recognition analysis of serum and brain tissue metabolite profile, a clear separation of the model group and control group was acquired for serum and brain tissue samples; the MGS (model + GS) group showed a tendency of recovering when compared to control group, which was consistent with behavioral and biochemical parameters. 39 and 40 potential biomarkers of brain tissues and serum samples, respectively, were identified and employed to explore the possible mechanism. Our work revealed that GS has significant protective effects on SD, and metabolomics is a useful tool for evaluating efficacy and elucidating mechanism in TCM.

Combination treatment with quercetin and resveratrol attenuates high fat diet-induced obesity and associated inflammation in rats via the AMPKα1/SIRT1 signaling pathway.

Diet-induced obesity is associated with systemic inflammation, which is considered to originate predominantly from the adipose tissue. Quercetin and resveratrol are two dietary polyphenols that exhibit anti-inflammatory properties and anti-insulin resistance when administered in isolation or combination (CQR). It remains unknown whether CQR reduces high fat diet (HFD)-induced obesity and inflammation in rats. In the current study, 46 male Wistar rats were divided into two groups, one of which was fed a normal diet (ND, 5.4% fat, w/w) and one of which was fed a HFD (45% fat, w/w) for 3 weeks. Following removal of the 12 most obesity-resistant rats from the HFD group, the remaining rats were divided into two sub-groups: A HFD group and a HFD+CQR group (administered 120 mg/kg/day resveratrol and 240 mg/kg/day quercetin). The results revealed that the HFD+CQR group had significantly lower body weights at 11 weeks compared with the HFD group and had significantly reduced visceral adipose tissue weights and adipocyte sizes. Serum lipid profiles were also significantly ameliorated in the HFD+CQR group. CQR attenuated the expression of systemic proinflammatory adipokines, including leptin, tumor necrosis factor-α, monocyte chemoattractant protein-1 and interleukin-6. It also reduced the recruitment of mast cells to the epididyotic adipose tissue (EAT). Furthermore, CQR reversed the HFD-induced suppression of 5'-adenosine monophosphate-activated protein kinase α1 (AMPKα1) phosphorylation and sirtuin 1 (SIRT1) expression in EAT. In conclusion, CQR may suppress obesity and associated inflammation via the AMPKα1/SIRT1 signaling pathway in rats fed a HFD.

[Effects of Chinese herbal medicines on spontaneous chronic pancreatitis in rats and the pathological relationships between formulas and syndromes].

OBJECTIVE: To investigate the effects of Guizhi Decoction, Chaihu Guizhi Decoction, Xiaochaihu Decoction and camostat on rat spontaneous chronic pancreatitis and the pathological relationships between formulas and syndromes. METHODS: Fifty-seven male WBN/Kob rats at age of 4 weeks were divided into five groups: untreated group (n=18), Guizhi Decoction-treated group (n=9), Chaihu Guizhi Decoction-treated group (n=9), Xiaochaihu Decoction-treated group (n=9) and camostat-treated group (n=12). The rats in each group were fed with corresponding drugs for 12 weeks. The pancreatic wet weight and histopathological changes of pancreatic tissue were observed every four weeks. Meanwhile, the expression level of pancreatitis-associated protein (PAP) in pancreas was detected by RT-PCR technique and immunohistochemical method. RESULTS: In the untreated group, the histopathological changes in pancreas were observed in rats at 12-week age, while such changes were absent in the Guizhi Decoction-treated group. The histopathological changes in pancreas were quite remarkable in rats at 16-week age in both the Xiaochaihu Decoction-treated and the camostat-treated groups. The expression level of PAP mRNA was lower in the Guizhi Decoction-treated group than those in the other groups. The PAP expressions were absent in rats at 12-week age in the Guizhi Decoction-treated and the Chaihu Guizhi Decocion-treated groups. CONCLUSION: Guizhi Decoction, Chaihu Guizhi Decoction, Xiaochaihu Decoction and camostat are all beneficial to prevention and cure of chronic pancreatitis, and Guizhi Decoction is the most effective one. It is speculated that Taiyang exterior syndrome may be the pathogenesis of basic syndrome may be the pathogenesis of basic syndrome of spontaneous chronic pancreatitis, and the expression of PAP may be its pathological basis.

Development of a pharmaceutical cocrystal with solution crystallization technology: Preparation, characterization, and evaluation of myricetin-proline cocrystals.

Myricetin shows low oral bioavailability (<10%) in rats due to poor aqueous solubility, although it has demonstrated various pharmacological activities such as those related to anticancer, anti-diabetes, and hepatic protection. To overcome this issue, in this study, pharmaceutical cocrystals were designed to efficiently deliver myricetin by oral administration. A 1:2 stoichiometric cocrystal of myricetin with proline was prepared successfully by solution crystallization based on the ternary phase diagram (TPD) principle, and it is presented as a new sphericity-like crystalline phase characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The formation of myricetin-proline cocrystals was a spontaneous and exothermic process, probably due to the supramolecular interactions between themselves, which were determined by Fourier transform-infrared spectroscopy (FT-IR). Consequently, the dissolution efficiency of myricetin from cocrystals was increased 7.69-fold compared with that of coarse myricetin, and the oral bioavailability of myricetin cocrystals in rats was enhanced by approximately 3.03 times compared with that of pure myricetin. The present study provides useful information for the potential application of cocrystal technology for water-insoluble drugs, especially flavonoid compounds.

Preparation and evaluation of chitosan-based nanogels/gels for oral delivery of myricetin.

A novel nanogel/gel based on chitosan (CS) for the oral delivery of myricetin (Myr) was developed and evaluated comprehensively. The particle size of the obtained Myr-loaded CS/ß-glycerol phosphate (ß-GP) nanogels was in the range of 100-300nm. The rheological tests showed that the sol-gel transition happened when the nanogels were exposed to physiological temperatures, and 3D network structures of the gelatinized nanogels (gels) were confirmed by Scanning Electron Microscopy. Myr was released from CS/ß-GP nanogel/gel in acidic buffers via a Fickian mechanism, and this release was simultaneously accompanied by swelling and erosion. Moreover, the nanogel/gel exhibited no cytotoxicity by MTT assay, and the oral bioavailability of Myr in rats was improved with an accelerated absorption rate after Myr was loaded into CS/ß-GP nanogel/gel. In summary, all of the above showed that CS/ß-GP nanogel/gel was an excellent system for orally delivering Myr.

[Efficacy of intravenous immunoglobulin in the adjuvant treatment of patients with severe sepsis: a Meta analysis].

Objective: To investigate the possibility of improving the prognosis of patients with severe sepsis by different kinds of intravenous immunoglobulin (IVIG). Methods: PubMed database, EMBase, Cochrane clinical trial database, CNKI, and Wangfang database etc were retrieved. The search time was from database creation to September 2015,which included all prospective studies of the effectiveness of IVIG compared with non-IVIG in all adult patients with severe sepsis. Main end-point parameter was total mortality rate; secondary end-point parameters were short-term (＜ 7 days) mortality,28-day mortality, length of intensive care unit (ICU) and hospital stay, and mortality due to septic shock or multiple organ failure (MOF). RevMan 5.3 was used for Meta analysis. Results: Finally,16 prospective studies including 12 randomized controlled trails (RCT) and 4 prospective cohort studies were enrolled, referred to 1 819 patients, 892 patients were in IVIG group, 927 patients receiving human albumin, placebo or blank control were in control group. Compared with the control group, IVIG could reduce the total mortality rate of patients with severe sepsis [relative risk (RR) =0.71,95％ confidence interval (95％CI) =0.57-0.87,P =0.001].After the high-risk research was eliminated, it was shown that the IVIG could reduce the total mortality rate in patients with severe sepsis (RR =0.80, 95％CI =0.65-0.98, P =0.03).But IVIG could not reduce the 28-day mortality rate (RR =0.60, 95％CI =0.35-1.04, P =0.07), short-term mortality rate (RR =1.06, 95％CI =0.76-1.46,P =0.74), the mortality rate of septic shock (RR =0.55, 95％CI =0.29-1.03, P =0.06) and the mortality rate of MOF (RR =0.91, 95％CI =0.63-1.33, P =0.64).In fact, the length of stay in ICU [weighted mean difference (WMD) =-0.02, 95％CI =-0.03-0.25, P =0.86] and the total length of stay in hospital (WMD =-2.34,95％CI =-7.05-2.37,P =0.33) were similar. In subgroup, the 28-day mortality rate of patients with severe sepsis in the IgM group (RR =0.50, 95％CI =0.25-1.01, P =0.05) was significantly lower than that of IgG group (RR =0.72, 95％CI =0.40-1.30, P =0.28). Conclusions: IVIG can reduce the total mortality rate of patients with severe sepsis. Compared with IgG, IgM-enriched IVIG has certain advantages in patients with severe sepsis, but cannot reduce the short-term mortality rate, mortality rate of septic shock and MOF, and also cannot shorten the length of ICU stay and the total length of hospital day.