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.

BackgroundRehabilitation for schizophrenia typically relies on pharmacological interventions， yet their efficacy in improving social function and quality of life remains limited. In recent years， non-pharmacological approaches have shown promise in enhancing rehabilitation outcomes. However， research on the effectiveness of psychomotor therapy specifically for young and middle-aged schizophrenic inpatients is limited. ObjectiveTo explore the effects of psychomotor therapy on the rehabilitation of young and middle-aged schizophrenic inpatients， and to provide a reference for treatment strategies. MethodsA total of 104 young and middle-aged schizophrenic inpatients who met the International Classification of Diseases，tenth edition （ICD-10） diagnostic criteria and hospitalized in the Fourth People's Hospital of Wuhu from June 2021 to June 2022 were selected. Patients were randomly divided into two groups of 52 each using random number table method. Both groups received treatment with risperidone tablets （2~4 mg/d） ， along with routine nursing care. Additionally， the research group received an extra 45~55 minutes of psychomotor therapy 2~3 times per week for 12 weeks. The control group received the same psychomotor therapy after the study. Positive and Negative Symptom Scale （PANSS）， Scales of Social-skills for Psychiatric Inpatient （SSPI） and Insight and Treatment Attitude Questionnaire （ITAQ） were used to assess the patients before the intervention and at 4^th， 8^th and 12^th week after the intervention. ResultsThe main effects of intervention at different time points for PANSS positive symptoms， negative symptoms and general psychopathology subscale scores， PANSS total score， SSPI score and ITAQ score were all statistically significant （F=33.989， 204.245， 82.817， 279.596， 26.144， 7.463， P<0.01）. Furthermore， statistically significant between-group differences were observed in PANSS negative symptoms and general psychopathology subscale scores， PANSS total score， SSPI score and ITAQ score （F=30.053， 5.306， 33.417， 33.013， 18.608， P<0.05 or 0.01）. Moreover， the interaction effect of time and group were statistically significant for PANSS positive symptoms， negative symptoms and general psychopathology subscale score， PANSS total score and SSPI score （F=3.472， 9.798， 3.843， 14.390， 20.661， P<0.05 or 0.01）. After 12 weeks of intervention， the research group exhibited statistically significantly lower PANSS total score and subscale scores compared with baseline （P<0.01）， while their SSPI total score was significantly higher than that of control group（P<0.01）. Additionally， compared with the control group， the research group had statistically significantly lower PANSS total score and subscale scores ， while their SSPI score was statistically significantly higher than those of control group（P<0.01）. ConclusionPsychomotor therapy may contribute to the improvement of the psychiatric symptoms and social function in young and middle-aged inpatients with schizophrenia， enhancing their rehabilitation outcomes. ［Funded by Health Commission Scientific Research Project of Wuhu （number， WHWJ2021y073）］

Objective:To discuss the effect of adipose-derived stem cell-derived exosomes(ADSC-Exos)on the migration ability of the macrophages RAW264.7,and to clarify its role in promoting function of the macrophages.Methods:The adipose tissue adjacent to epididymis of the SD rats was isolated to perform primary culture of the adipose-derived stem cells(ADSCs).The adipogenic and osteogenic differentiation induction was conducted,and the multidirectional differentiation potential of the ADSCs was detected by oil Red O and Alizarin red staining.Western blotting and immunofluorescence methods were used to detect the positive expressions of the ADSCs markers CD29 and CD44;the ADSC-Exos were extracted by Exos isolation kit,and the morphology,size,and distribution of particle size of the ADSC-Exos were examined by transmission electron microscope and nanoparticle tracking analyzer;the expression levels of exosome-specific markers CD9 and TSG101 proteins in the ADSC-Exos were detected by Western blotting method;the uptake of ADSC-Exos by the macrophages was observed by tracing method.The macrophages RAW264.7 were divided into control group,10 mg·L-1 ADSC-Exos group,20 mg·L-1 ADSC-Exos group,and 40 mg·L-1 ADSC-Exos group.The activities of the macrophages in various groups were detected by 5-ethynyl-2'-deoxyuridine(EdU)staining;the number of migration macrophages in various groups was detected by Transwell chamber assay;the adhesion of macrophages in various groups was observed by fluorescence microscope.Results:After 24 h of primary culture,the ADSCs adhered to the wall and exhibited scattered,elongated shapes;after 7 d of culture,the adherent cells showed a comb-like,vortex-like orderly arrangement,resembling fibroblasts;after 10 passages,the irregular morphology of the ADSCs and decreased proliferation rate were found.The isolated ADSCs showed potential for the osteogenic and adipogenic differentiation,and the expressions of CD29 and CD44 proteins were positive.The transmission electron microscope observation resuls showed that the ADSC-Exos appeared disc-shaped,and the main peak of particle size distribution was around 132 nm.The CD9 and TSG101 proteins were positively expressed in the ADSC-Exos,indicating successful extraction.The fluorescence microscope results showed red fluorescence signals around the nuclei of the RAW264.7 cells,indicating the uptake of ADSC-Exos by the macrophages.Compared with control group,the rates of EdU positive cells in 10,20,and 40 mg·L-1 ADSC-Exos groups were significantly increased(P<0.05);compared with 10 mg·L-1 ADSC-Exos group,the rate of EdU positive cells in 20 mg·L-1 ADSC-Exos group was significantly increased(P<0.05).Compared with control group,the numbers of migration cells in 10,20,and 40 mg·L-1 ADSC-Exos groups were significantly increased(P<0.05);compared with 10 mg·L-1 ADSC-Exos group,the numbers of migration cells in 20 and 40 mg·L-1 ADSC-Exos groups were significantly increased(P<0.05).Compared with control group,the numbers of the adherent macrophages in 10,20,and 40 mg·L-1 ADSC-Exos groups were significantly increased(P<0.05);compared with 10 mg·L-1 ADSC-Exos group,the number of adherent macrophages in 20 mg·L-1 ADSC-Exos group was significantly increased(P<0.05).Conclusion:The ADSC-Exos can be internalized by the macrophages and they can enhance the migration ability of the macrophages by affecting the cell adhesion.

Objective:To explore the predictive value of transvaginal ultrasound measurement of cervical length (CL) in the first and second trimester on spontaneous preterm birth in singleton pregnant women.Methods:This study retrospectively recruited 2 254 singleton pregnancies without severe comorbidities at Peking University First Hospital from January 2019 to June 2019. CL was measured for all subjects using transvaginal ultrasound in the first (11-13 +6 weeks) and second trimester (21-23 +6 weeks). Differences in CL between women with preterm (preterm group) and full-term delivery (full-term group) as well as the CL during the first and second trimester were compared. The independent risk factors for preterm birth and the predictive value of CL in the first and second trimester for spontaneous preterm birth were also explored. Fisher's exact test, t-test, χ2 test, and logistic regression analysis, etc, were adopted for statistical analysis. Results:(1) For the 2 254 subjects, CL measured in the first trimester and second trimester were (36.1±4.2) mm (22.4-52.6 mm) and (36.9±5.3) mm (2.9-59.7 mm), respectively. The incidence of short cervix in the first trimester and second trimester were 0.31% (7/2 254) and 1.46% (33/2 254), respectively. When CL was ≤25.0 mm ( OR=43.92, 95% CI:6.83-282.49) or >25.0-≤30.3 mm ( OR=6.59, 95% CI:1.97-22.0) in the first trimester, the risk of short cervix increased in the second trimester (both P<0.05). (2) The total incidence of preterm delivery was 3.06% (69/2 254). CL and the incidence of short cervix did not differ significantly in the first trimester between the preterm and full-term group [(35.2±4.5) and (36.1±4.1) mm, t=－1.78, P=0.076; 1.5% (1/69) and 0.3% (6/2 185), χ 2=2.98, P=0.084]. Compared with the full-term group, CL was shorter and the incidence of short cervix was higher in the second trimester in the preterm group [(33.6±6.7) vs (37.0±5.2) mm, t=－5.12;8.7% (6/69) vs 1.2% (27/2 185), χ 2=25.80, P<0.001]. (3) Multivariate regression analysis showed that age ≥35 years ( OR=2.05, 95% CI:1.22-3.46), history of spontaneous preterm birth ( OR=25.25, 95% CI:5.01-127.28), conception assisted by reproductive technology ( OR=10.39, 95% CI:2.39-50.33), and short cervix during the second trimester were independent risk factors for premature delivery. (4) There was no significant difference in the risk of preterm delivery when comparing to those with CL≤25.0 mm, >25.0-≤30.3 mm, >30.3-≤33.0 mm, >33.0-≤35.7 mm, >35.7-≤38.7 mm women with CL>38.7 mm during the first trimester (all P>0.05). The risk of premature delivery was relatively increased for those with CL≤25.0 mm,>25.0-≤29.5 mm, >29.5-≤33.6 mm, >33.6~≤36.8 mm, >36.8~≤40.1 mm during the second trimester compared to those with CL>40.1 mm [ OR (95% CI):17.64 (4.99-62.32), 6.89 (2.11-22.55), 3.58 (1.34-9.59), 4.04 (1.58-10.32), 3.34 (1.28-8.67), respectively , all P<0.05]. (5) When CL≤25.0 mm and ≤29.5 mm in the second trimester were used as the cut-off value, the prediction of preterm delivery was with a sensitivity of 8.70% and 17.39%, specificity of 98.80% and 95.29%, positive predictive value of 18.20% and 10.43%, negative predictive value of 97.16% and 97.34%, and the accuracy rate of 96.01% and 92.90%, respectively. Conclusions:There were no significant differences in CL and the incidence of short cervix during the first trimester among women with preterm or full-term delivery. CL in the first trimester is not an independent risk factor for preterm birth, but the risk of short cervix in the second trimester is increased when CL≤30.3 mm in the first trimester. The shorter the cervix during the second trimester, the greater the risk of preterm birth.

ObjectiveTo analyze the gender differences in the pathogen distribution and drug susceptibility of bacteria causing urinary tract infection among psychiatric inpatients in a hospital in Guangzhou， and to provide a basis for clinical diagnosis and rational use of drugs in treatment. MethodsClinical data of 326 psychiatric patients complicating urinary tract infection in a hospital in Guangzhou from 2019 to 2020 were retrospectively analyzed， including 126 males and 200 females. Data including gender， age， identification results of urinary tract pathogens from urine samples and drug susceptibility results were collected. The differences in bacterial distribution and drug resistance rate of urinary tract infection pathogens in patients of different genders were analyzed. ResultsA total of 326 strains of urinary tract infection bacteria were isolated， including 103 strains （31.60%） of multi-drug resistant bacteria. Male and female urinary tract infection in patients with multi-drug resistant bacteria were detected 52 strains （41.27%） and 51 strains （25.50%）， the detection rate of multi-drug resistant bacteria in female patients was significantly higher than that in male patients， with statistical difference （χ²=8.895， P<0.01）. In terms of bacterial distribution， the composition ratio of Escherichia coli in female patients was higher than that in male patients （χ²=14.794）， while the composition ratio of Acinetobacter baumannii and Pseudomonas aeruginosa was lower than that in male patients （χ²=13.665， 4.054）， with statistical difference （P<0.05 or 0.01）. The drug susceptibility results showed that Escherichia coli isolated from female patients were less resistant to various antibiotics such as ampicillin/sulbactam， aztreonam， cefepime， ceftazidime， levofloxacin， imipenem and meropenem than those from male patients （χ²=5.028~17.680， P<0.05 or 0.01）. ConclusionThe prevalence rate and bacterial distribution of psychiatric patients complicating urinary tract infection differ between patients of different genders， furthermore， the rate of drug resistance for Escherichia coli is lower in female patients than that in male patients.

Objective:To explore the independent risk factors of poor healing of surgical incisions in patients with drainage tube removal after thoracic and abdominal surgery and establish a risk prediction model for poor healing of surgical incisions.Methods:Using the convenient sampling method, a total of 545 patients who underwent thoracic and abdominal surgery in the Affiliated Hospital of Qingdao University were selected from July to December 2020. The patients were divided into the poor wound healing group ( n=87) and the non-incision poor healing group ( n=458) according to whether they had poor wound healing. Logistic regression analysis was used to analyze the risk factors of poor healing of surgical incisions and build a risk prediction model. The receiver operating characteristic (ROC) area under the curve was used to test the model to predict the effect and 230 patients were selected to verify the model prediction effect. Results:In this study, 5 factors including duration of exudation, serum albumin, incision infection, the volume of exudation during catheterization and catheterization time were finally included to construct a risk prediction model. The model formula was Z=4.608+4.855× duration of exudation +3.173× serum albumin +3.739× infection of the incision +2.271×the volume of exudation during catheterization + 0.466× catheterization time. The area under ROC curve of this model was 0.773 (95% CI: 0.678 - 0.868). The maximum value of Youden index was 0.549, the sensitivity was 0.742 and the specificity was 0.807. Conclusions:The risk prediction model of poor incision healing after drainage tube removal for patients undergoing thoracic and abdominal surgery can better predict the risk of poor incision healing and provide a basis for clinical medical staff to take preventive management measures for high-risk patients in time.

OBJECTIVE： To investigate the acute toxicity， long-term toxicity， skin irritation and anaphylaxis of Bee venom （BV） plastics， and to evaluate its preclinical safety. METHODS： The acute toxicity of BV plastics to rats was investigated after administration of high-dose， medium-dose and low-dose （144， 96， 48 mg/kg） of BV plastics. The long-term toxicity of BV plastics was investigated by continuous administration of high-dose， medium-dose and low-dose （72， 48， 24 mg/kg） of BV plastics for 28 days. The irritation of intact and damaged skin in rabbits with 8 mg/kg BV plastics was investigated by using the self-control method of left and right homologous body. The skin anaphylaxis of guinea pig were investigated after sensitized with 15 mg/kg BV plastics on the left back （on 0， 7th， 14th day） and stimulated with 15 mg/kg BV plastics on the right back. RESULTS： During the acute toxicity experiment with BV plastic，the weight of rats and the changes of viscera were normal，and there was no relevant toxic reaction. Long-term toxicity test results showed that no significant pathological changes were observed at 24 h after the last administration； the spleen index  of rats in BV low-dose group， testicular index in middle-dose group and epididymis index in high-dose and middle-dose groups were significantly increased， while PT in plasma of rats in BV medium-dose and low-dose groups was significantly prolonged （P＜0.05）. There were no abnormal changes in organ appearance， other organ index， coagulation index and blood biochemical index. All above indexes became normal at the end of 2-week recovery period. Skin irritation test showed that BV plastics could cause slight erythema and obvious scab on the skin of rabbits which along with little irritation on intact or damaged skin. Skin anaphylaxis test showed that BV plastics produced mild erythema in the skin of guinea pigs， belonging to light allergy. CONCLUSIONS： No acute or long-term toxicity is observed after transdermal administration of BV plastics， which is safe and only causes mild irritation and irritability to skin， indicating there is good safety of the plastic under experiment doses.

Objective To evaluate the effects of sodium-glucose cotransporter 2 ( SGLT2) inhibitors on the stroke risk for patients with type 2 diabetes mellitus (T2DM). Methods A systemic meta-analysis including 30 random control trails ( RCTs) was performed to compare the risk of stroke between type 2 diabetic patients treated with SGLT2 inhibitors and control drugs. Then their bias risk and quality were assessed and meta-analysis was conducted using Stata12.0 software. Results Thirty RCTs enrolling 74456 participants were selected for meta-analysis. The stroke incidence in the group receiving SGLT2 inhibitor monotherapy or combination therapy did not significantly differ from that in control group, with relative risk (RR) 1.01 (95％CI 0.93-1.10, P=0.978) and 1.00 (95％CI 0.92-1.09, P=0. 874 ) , respectively. Three SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin did not increase the risk of stroke, with similar RR values ( RR=0.91, 0.99, 1.13, respectively) . Subgroup analyses showed that there was no correlation between SGLT2 inhibitors and stroke risk in different gender, age, diabetes duration, body mass index, or HbA1C levels. Conclusions Whether administered as monotherapy or add-on therapy, SGLT2 inhibitors did not increase stroke incidence, and there were no significant within-class differences.

OBJECTIVE:To provide reference for rational use of antibiotics to treat Pseudomonas aeruginosa (PA) infection in the clinic. METHODS:Resistant rate of PA in our hospital during 2011-2015 were analyzed retrospectively. Antibiotics use densi-ty(AUD)of 10 commonly used antibiotics were analyzed statistically,and the correlation of resistant rate with AUD was investi-gated by Spearman correlation analysis. RESULTS:One thousaud and eleven strains of PA were isolated in our hospital during 2011-2014,detection rate of PA always occupied the top 5 place. Top 3 antibiotics in the list of AUD were levofloxacin,ceftazi-dime,cefoperazone sodium and tazobactam sodium. AUD of piperacillin sodium and tazobactam sodium,levofloxacin,ciprofloxa-cin and meropenem were positively correlated with resistant rate of PA(r were 1.000,0.900,1.000,1.000,P<0.05). AUD of ce-foperazone sodium and tazobactam sodium were negatively correlated with resistant rate of PA(r=-0.900,P<0.05). AUD of imi-penem and cilastatin sodium,ceftazidime,gentamicin,aztreonam and amikacin had no correlation with resistant rate of PA(P>0.05). CONCLUSIONS:There is correlation between AUD of antibiotics and resistant rate of PA. It is of important significance to detect resistant rate of PA and the use of antibiotics regularly. Antibiotics should be selected cautiously in accordance with bacterial monitoring data,results of drug sensitivity tests,the amount and resistant rate of antibiotics,etc,in order to reduce resistant PA.