ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

Objective:Analyze the mediating and moderating effects of the relationship between food intake and blood glucose levels.Methods:This study uses data from the China Health and Nutrition Survey project in the survey 2018, involving 11 043 adults aged 18 years or older, who have complete dietary data, waist circumference (WC), glycated hemoglobin A1c (HbA1c) indicators, and other key variables. Food consumption data was gathered via three consecutive 24-hour dietary recalls and weighing accounting method, which included two weekdays and one weekend day. The average daily intake of various foods and total energy intake were calculated. The mediation effect and moderation effect analysis were conducted using simple mediation models, direct moderation effect models, and moderated mediation analysis theoretical models. The confidence interval method (bootstrap method) was performed for testing and analysis.Results:A total of 4 951 males and 6 092 females were included in the stratified analysis by gender. The mediating effects on the rice, wheat, and red meat→WC→HbA1c were all statistically significant in males. The standardized coefficients were -0.009 ( P<0.001), 0.013 ( P<0.001), and -0.005 ( P=0.008), respectively. In females, the mediating effect on the wheat→WC→HbA1c was statistically significant, and the standardized coefficient was 0.017 ( P<0.001); the impact of red meat intake on HbA1c is negatively regulated by the intake of dark vegetables, with a direct moderating effect; the standardized coefficient of the interaction term between red meat and dark vegetables was -0.024 ( P=0.008). Dark vegetables have a moderated mediator on the pathway from rice to WC and HbA1c ( a3b1=-0.003, P=0.041) in males. The mediating effect of WC is negatively regulated by the intake of dark vegetables (mediation effect difference U1/-1=-0.006, P=0.048). Dark vegetables showed a moderated mediator on the pathway from wheat to WC and HbA1c ( a3b1=-0.004, P=0.045) in females. The mediating effect of WC is negatively regulated by the intake of dark vegetables (mediation effect difference U1/-1=-0.009, P=0.049). Conclusions:Changes in WC indicators caused by rice, wheat, and red meat intake. WC could mediate between rice, wheat, red meat, and HbA1c. Dark vegetables directly or indirectly regulate HbA1c levels by interacting with rice, wheat, and red meat.

Objective:To construct an evaluation system for clinical thinking ability of general practitioners in the treatment of multimorbidity.Methods:This was a cross-sectional study. The draft of evaluation indexes for clinical thinking ability of general practitioners in treatment of multimorbidity was preliminary developed through literature review, collation, analysis and discussion. Nineteen clinical and teaching experts of general practice were selected for consultation via anonymous convenient sampling. From January to June 2022, 2 rounds of expert consultation were conducted using the Delphi method. During the first round of consultation, according to the survey feedback, we modified and improved the evaluation system of general practitioners′ clinical thinking ability for multi-disease co-treatment. During the second round, experts were asked to assess the importance of each index, and to calculate the weight of each index accordingly. Questionnaires were sent to experts via letters. The content of the questionnaires encompasses the basic information of experts, evaluation for various indexes and relevant opinions. The mean value of importance assignment ≥3.5, coefficient of variation ≤0.25 and the full score frequency ≥30% were taken as the criteria. Indexes unsatisfying the criteria were removed, so that the final index system could be constructed.Results:The average age of 19 experts was 50.2 years old, 9 of them were male. A total of 2 rounds of expert consultation were conducted, 19 questionnaires were issued in each round, and 19 effective questionnaires were received afterwards. In the first round of consultation, 10 experts put forward revised opinions, and some indexes were adjusted according to the definition criteria and the discussion of the research group. In the second round of consultation, 3 experts put forward suggestions for modification. According to the definition criteria, no need to delete the indexes. After discussion by the research group, some indexes were adjusted, and finally an evaluation system of clinical thinking ability for multi-disease co-treatment of general practitioners was established, including 4 first-level indexes and 30 second-level indexes. The weights of the 4 first-level indexes in descending order were "overall thinking ability" (38.01%), "diagnostic thinking ability" (33.96%), "evidence-based thinking ability" (14.75%), and "critical thinking ability" (13.28%). Among the 30 secondary indexes, the top 5 were "ability to identify and handle priority emergency incidents" (5.04%), "risk assessment and critical illness identification ability" (4.63%), "emergency referral ability" (4.61%), "communication and expression ability" (4.57%), and "standardized diagnosis and treatment ability" (4.23%).Conclusion:This study successfully constructed an evaluation system for clinical thinking ability of general practitioners in the treatment of multimorbidity.

Background Changes in cognitive function exist before the onset of clinical Parkinson's disease. However, studies on association between cognitive function and prodromal Parkinson's disease (pPD) are limited. Objective To estimate probability of pPD and assess its association with global and domain cognitive function in Chinese elders. Methods Data were drawn from the Community-based Cohort Study on Nervous System Disease 2018 (baseline) and 2020 (follow-up). We selected 3911 residents aged 55 and above who participated the two waves, without Alzheimer's disease and Parkinson's disease, and with completed information on demographics, disease history, cognitive function test, and risk factors of Parkinson's disease. Cognitive function was assessed using the Chinese version of Montreal Cognitive Assessment Scale. Calculation of probability of pPD and assessment of possible (probability between 30% and <80%) or probable (probability ≥80%) pPD were performed according to the criteria published by the International Parkinson and Movement Disorder Society. Multiple linear regression model was employed to analyze the association between baseline cognitive function and follow-up probability of pPD. Results The medians of scores of baseline global cognitive function and cognitive domains in terms of memory, execution, visuospatial function, language, attention, and orientation were 23, 12, 9, 6, 5, 14, and 6, respectively. The median of follow-up probability of pPD was 0.87%, and the proportion of participants with possible or probable pPD was 0.4%. The differences in the distribution of follow-up probability of pPD were significant in groups by baseline global cognitive score quartiles (χ²=21.68, P<0.001). A higher baseline global cognitive score was considerably related to a lower follow-up probability of pPD, b(95%CI)=0.994(0.988~0.999), P=0.040. After adjusting for selected confounders, the results of multiple linear regression analyses showed that the probability of pPD in the highest quartile group was decreased by 10.7% (b=0.893, 95%CI: 0.794-0.992, P=0.034) relative to the lowest quartile group, and the trend was significant (trend P=0.031). Higher baseline index scores of execution, attention, and orientation were highly related to a lower follow-up probability of pPD (all P<0.05). Conclusion Declines in global cognitive function and cognitive domains of execution, attention, and orientation may associate with a higher probability of pPD in middle-aged and elderly population, which suggests the significance of cognitive intervention in early stage for pPD prevention.

Objective: To understand the differences in the application of three distant vision examination methods in children, so as to provide a reference for developing a unified distant vision examination for this population. Methods: The study involved 98 children aged 4 to 16 years who visited the ophthalmology department of a children s hospital in Anhui Province between August 15 and 25, 2022. Vision was measured using the distant vision test method specified in the 2014 National Student Physical Fitness and Health Survey (V1), the 2019 National Student Physical Fitness and Health Survey (V2), and Specification for Screening of Refractive Error in Primary and Secondary School Students (WS/T 663-2020) (V3). The paired samples McNemar s test and Wilcoxon test were performed to compare the detection rate of poor vision and the difference between the visual acuity test results of the three methods. Results: The results of the 98 children examined according to V1, V2, and V3 showed that the M (P25, P 75 ) of the right eye were 4.8（4.6，5.0），4.8（4.7，5.0），and 4.8（4.7，5.0）while the left eye visual acuity M ( P 25 , P 75 ) were 4.8 （4.6，5.0），4.9（ 4.7 ，5.0），and 4.9（4.7，5.0），respectively. The rates of poor visual acuity detection for the right eye were 63.3%, 58.2% and 58.2 % for V1, V2, and V3, respectively, while for the left eye, they were 58.2%, 54.1% and 53.1%, respectively. McNemar test results showed that there were no statistically significant differences in the rates of poor visual acuity detection between the right and left eyes for V1 vs. V2, V1 vs. V3, and V2 vs. V3 (left eyes： χ 2=2.25，2.29，0.00，right eyes： χ 2=3.20，3.20，0.00， P >0.05).Wilcoxon test results indicated that there were statistically significant differences between the right and left eye visual acuity groups for V1 vs. V2 and V1 vs. V3 (left eyes： Z =-4.15，-4.60, right eyes： Z = -4.70，-4.99, P <0.01). Conclusion Irrespective of whether the starting visual standard starts at row 4.0 or 5.0, different standards of visual standard passage have an impact on the visual acuity results. It is recommended that existing methods of screening for distance vision are standardized.

Objective:To analyze probability of prodromal Parkinson's disease (pPD) and assess the association between global cognitive function and cognitive domain function and probability of pPD in ≥55 years old middle-aged and elderly people in Hebei, Zhejiang, Shaanxi and Hunan Provinces in China.Methods:Data were collected from dataset of the Community-based Cohort Study on Nervous System Disease 2020. We selected 4 634 Alzheimer disease and Parkinson's disease free persons aged ≥55 years with completed information on demographics, disease history, cognitive test, and risk factors of Parkinson's disease for this study. Cognitive function was assessed using Montreal Cognitive Assessment Scale (Chinese version). Calculation of probability of pPD and assessment of possible/probable pPD were performed according to the criteria published by the International Parkinson and Movement Disorder Society. Multivariate linear regression model was used to analyze the association between cognitive function and probability of pPD.Results:The M ( Q1, Q3) of global cognitive function and cognitive domains in terms of memory, execution, visuospatial function, language, attention and orientation were 25 (20, 30), 13 (11, 15), 10 (7, 12), 6 (4, 7), 5 (4, 6), 15 (12, 18) and 6 (6, 6) points, respectively. The M( Q1, Q3) of probability of pPD was 0.42% (0.80%, 1.73%), and the proportion of the study subjects with possible/probable pPD was 0.4%. Differences in the distribution of probability of pPD were significant among groups by total cognitive score quartiles ( P<0.001), and the difference in proportions of study subjects with possible/probable pPD was significant and showed decline trend ( P=0.001). After adjusted for confounders, the results of multivariate linear regression analyses showed that probability of pPD in the Q2, Q3 and Q4 group decreased by 23.4%, 31.2% and 20.1% compared with Q1 group, and corresponding β values were 0.766 (95% CI: 0.702-0.836), 0.688 (95% CI: 0.631-0.751) and 0.799 (95% CI: 0.730-0.875), respectively, the trend was significant ( P<0.001). Higher index scores of execution, visuospatial function, language, attention and orientation were highly related to lower probability of pPD ( P<0.001). Conclusion:Declines in global cognitive function and cognitive domains of execution, visuospatial function, language, attention and orientation might increase the probability of pPD in middle-aged and elderly people, suggesting the importance of cognitive intervention in early stage for pPD prevention.

Sepsis is an inflammatory disorder syndrome caused by the infection of pathogenic microorganisms, which organ dysfunction due to the dysregulated response of the body to the infection. Sepsis is a dangerous disease with a high fatality rate. The liver, an important organ involved in human biological transformation, energy metabolism, and cytokine production. Its role in sepsis is like a "double-edged sword" because the liver acts as not only an important defense line of the body against microorganisms but also a common target of inflammatory disorders and damage, making it one of the most vulnerable organs in sepsis. The liver contributes to pathogen clearance through immune responses, but the resulting inflammatory reactions can also lead to tissue and organ damage. Sepsis liver injury is an independent risk factor for poor prognosis in sepsis patients, and preventing its occurrence and promoting early recovery can partially inhibit disease progression and reduce mortality rates. However, the pathogenesis of sepsis liver injury is not yet fully understood, and there is a lack of early and effective means of diagnosis and treatment. In-depth research on its pathogenesis will provide a better understanding of its occurrence and development, further supporting the theoretical basis for the treatment of sepsis liver injury and identifying some new targets for sepsis treatment, ultimately reducing the mortality of sepsis.

Objective:To observe the characteristics of choroidal thickness in patients with macular edema secondary to superior temporal branch retinal vein occlusion (BRVO-ME).Methods:A retrospective control study. From November 2020 to September 2021, 30 patients (30 eyes) with BRVO-ME (BRVO-ME group) were diagnosed by ophthalmology examination in Department of Ophthalmology, The Affiliated Hospital of Chengde Medical College and 14 healthy volunteers (28 eyes) were enrolled in the study. The choroidal thickness of macular area was measured by enhanced deep imaging technique of frequency domain optical coherence tomography. According to the subdivision of the diabetic retinopathy treatment group, the choroid within the 6 mm of the macular fovea was divided into three concentric circles with the macular fovea as the center, namely, the central area with the diameter of 1 mm, the inner ring of 1-3 mm and the outer ring of 3-6 mm. The inner ring area and the outer ring area are divided into upper, lower, nasal and temporal sides, respectively, which are denoted as S3, I3, N3, T3 and S6, I6, N6, T6, totaling 9 areas. To observe the distribution characteristics of choroidal thickness in different regions of two groups of eyes. The choroidal thickness of different macular regions was compared by independent sample t-test. Results:The choroidal thicknesses in the central area, S3, T3, I3, N3, S6, T6, I6, and N6 of the eyes in the control group and BRVO-ME group were 214.11±56.04, 207.89±57.92, 214.07±54.82, 207.14±61.54, 180.18±53.53, 204.25±59.60, 193.93±51.50, 190.54±51.21, 139.82±39.84 μm and 258.00±71.14, 256.43±68.70, 252.07±72.97, 244.37±68.49, 243.10±70.93, 247.20±68.36, 221.00±61.28, 223.77±58.64, 183.20±60.15 μm. In both groups, the choroidal thickness was the thickest in the central area, gradually thinning to the nasal side and temporal side, and the nasal choroidal thickness was thinner than other regions, and N6 area was the thinnest. Compared with the control group, the choroidal thickness of central area, S3, T3, I3, N3, S6, I6 and N6 in BRVO-ME group were significantly thicker ( t=-2.899, -2.229, -2.172,-3.250, -2.543, -2.292, -3.214; P<0.05), there was no significant difference in T6 area ( t=-1.814, P=0.075). Conclusion:The choroidal thickness of macular area in patients with BRVO-ME is thicker than that in normal subjects.

OBJECTIVE To investigate the protective effect and potential mechanism of Arisaema Cum Bile on acute liver injury induced by carbon tetrachloride （CCl4） in mice. METHODS Fifty mice were randomly divided into normal group， model group， positive control group （Biphenyl diester dropping pills， 150 mg/kg）， Arisaema Cum Bile low-dose and high-dose groups （0.78， 2.34 g/kg）， with 10 mice in each group. The mice in each group were given relevant medicine intragastrically， once a day， for 7 consecutive days. Two hours after the last administration， those groups were given intraperitoneal injection of 0.2% CCl4-olive oil solution to induce acute liver injury model except for normal group. Seventeen hours after intraperitoneal injection， the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF- α）， and malondialdehyde （MDA）， superoxide dismutase （SOD） in liver tissue were measured with kit method. The hepatic index was detected. The pathological changes of liver tissue were observed by HE staining， and the degree of liver injury was scored quantitatively. The mRNA expressions of TNF-α and IL-6 in liver tissue were detected by real-time fluorescence quantitative PCR； the protein expressions of Janus kinase 2 （JAK2）， signal transducer and activator of transcription protein 3 （STAT3） and nuclear factor-κB p65 （NF-κB p65） in liver tissue were detected by Western blot assay. RESULTS Compared with normal group，the levels of ALT， AST， IL-6， TNF-α and MDA， the hepatic index were increased significantly （P＜0.05）， while the level of SOD was decreased significantly （P＜0.05）； the mRNA E-mail：qhwang668@sina.com expressions of IL-6 and TNF-α， and the protein expressions of JAK2， STAT3 and NF-κB p65 were up-regulated significantly （P＜0.05）； the pathological observation of liver tissue showed that the structure of hepatic cord was seriously disordered， there were many inflammatory cells infiltration of liver cells， and the liver injury score was significantly increased （P＜0.05）. Compared with model group， pathological changes and above indexes in mice were improved significantly in Arisaema Cum Bile low-dose and high-dose groups （P＜0.05）. CONCLUSIONS Arisaema Cum Bile has a protective effect on CCl4-induced acute liver injury in mice， which may be related to the inhibition of inflammatory response mediated by JAK2/STAT3/NF-κB signal pathway and antioxidant stress.