OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

To explore the understanding of the target population regarding the Get Active Questionnaire for Pregnancy(GAQ-P)and the Companion Health Care Provider Consultation Form for Prenatal Physical Activity(cHCP-CF-PPA)in the Chinese context,and to verify the consistency of the Chinese version of the prenatal physical activity dual screening questionnaire with the original version in terms of language expression,27 pregnant women and 12 healthcare providers were selected from Obstetrics and Gynecology Hospital,Fudan University during Aug and Oct 2023,and were interviewed using purposive sampling.Two rounds of cognitive interviews were conducted.The first round revealed that some respondents experienced ambiguities in understanding the meanings of 5 items in the questionnaire.Following modifications,the second round indicated that the revised items were consistent in meaning with the original questionnaire.Cognitive interviews can facilitate the adaptation of the prenatal physical activity dual screening questionnaire to the Chinese cultural context,improve the understanding of the questionnaire items among the target population,and promote the localization of the screening tool.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

Objective To systematically review and quantitatively analyze the safety of biologic agents for the clinical treatment of psoriasis during pregnancy and lactation.Methods The literature from start of database to June 27,2023,was searched in MEDLINE(PubMed),Embase,Cochrane Library,and Web of Science by two researcher.Quality of included studies was assessed by the quality evaluation tool of case series from Australian JBI Evidence Based Healthcare Centre.According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA),a systematic review and was conducted to assess pregnancy or breastfeeding outcomes in psoriasis patients exposed to biologics within 3 months prior to pregnancy,during pregnancy or breastfeeding.Data on pregnancy and exposure characteristics were pooled,and the prevalence of adverse pregnancy outcome was summarized using a random effects model.Results A total of 54 studies involving 1206 pregnancies in 1177 female patients with psoriasis exposed to biologic agents were included in the analysis.Systematic review results demonstrated that the majority of the exposures were limited to early pregnancy,with pooled spontaneous abortion rates,elective abortion rates,overall mortality,preterm birth rates,incidence of low birth weights,and congenital anomalies similar to those of general population(P>0.05).Furthermore,no serious adverse reactions were reported during lactation.Conclusions The use of biologic agents in pregnant and breastfeeding women with psoriasis does not significantly increase the risk of adverse pregnancy outcomes and does not affect neonatal health or growth.However,the limited available safety data underscores the necessity of further studies to establish the relationship between psoriasis,biologic agents,and pregnancy/lactation outcomes,thereby providing comprehensive guidance for clinical practice.

AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P＞0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.

AIM To establish the preparation process and quality standard for Zhenggu Pills.METHODS With decoction time,decoction frequency and water addition as influencing factors,comprehensive score for extract yield and transfer rates of epicatechin and naringin as an evaluation index,the decoction process was optimized by orthogonal test.With sugarless paste relative density,medicinal powder fineness,sugarless paste-corn starch ratio,drying temperature and drying time as influencing factors,soft material traits,pill formability,moisture and disintegration time limit as evaluation indices,the formability process was optimized by single factor test.TLC was adopted in the qualitative identification of Dipsaci Radix,salt-processed Psoraleae Fructus,cooked Rhei Radix et Rhizoma and Notoginseng Radix et Rhizoma.HPLC was used for the content determination of paeoniflorin and naringin.RESULTS The optimal decoction process was determined to be 0.5 h for decoction time,two times for decoction frequency,and 10 times for water addition,the comprehensive score was 0.93.The optimal formability process was determined to be 1.21-1.22 for sugarless paste relative density,80 mesh for medicinal powder fineness,1∶0.17-1∶0.18 for sugarless paste-corn starch ratio,70 ℃ for drying temperature,and 24 h for drying time,good soft material traits and pill formability were observable,and moisture and disintegration time limit accored with 2020 edition of Chinese Pharmacopoeia requirements.The TLC spots were clear without negative interference.Two constituents showed good linear relationships within 61.30-490.41 μg/mL(r=0.999 8)and 3.27-26.18 μg/mL(r=0.999 8),whose average recoveries were 100.15％and 98.15％with the RSDs of 0.55％and 2.30％,respectively.CONCLUSION This stable,reliable and specific method can be used for the production and quality evaluation of Zhenggu Pills.

Aim To explore the mechanisms of PM2.5 exposure exacerbating bleomycin(BLM)-induced idio-pathic pulmonary fibrosis(IFP)by regulating ferropto-sis via nuclear factor 2 related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase(GPX)4 axis.Methods Forty C57BL/6J mice were randomized into the control,BLM,PM2.5,BLM+PM2.5 and sulforaphane(SFN,Nrf2 agonist)groups,with eight mice in each group.PM2.5 expo-sures were conducted to the BLM-induced IPF mice for two weeks.The lung function was measured,and the content of hydroxyproline(HYP)in lung tissue and the pathomorphology of lungs were observed.Reactive oxygen species(ROS),malondialdehyde(MDA),ferrous ion(Fe2+)and glutathione(GSH)of the lung tissue were measured by ELISA.The mRNA and pro-teins levels of Nrf2,SLC7A11,GPX4,collagen typeⅠ(COL-1),α-smooth muscle actin(α-SMA)were measured by quantitative polymerase chain reaction(qPCR)and Western blot.Results Compared with the control group,the lung function of mice was signif-icantly reduced(P＜0.01)in the BLM and PM2.5 groups,while lung tissue showed the characteristic pathological changes of pulmonary fibrosis such as a large number of inflammatory cell infiltration,alveolar wall fracture,thickening,collagen deposition,and sig-nificantly increased HYP,Fe2+,ROS,MDA(P＜0.05,P＜0.01),genes and proteins of COL-1,α-SMA(P＜0.01);and decreased GSH,Nrf2,SLC7A11,GPX4 genes and proteins(P＜0.05,P＜0.01).The above-mentioned lesions were markedly aggravated in the BLM+PM2.5 group compared with the BLM(P＜0.05)and PM2.5 groups(P＜0.01),and were also improved in the SFN group(P＜0.05,P＜0.01).Conclusions PM2.5 exposures can exac-erbate IPF-induced IPF in mice,and the regulating of Nrf2/SLC7 A1 1/GPX4 axis and ferroptosis might be in-volved in the related mechanisms.

AIM To establish the preparation process and quality standard for Zhenggu Pills.METHODS With decoction time,decoction frequency and water addition as influencing factors,comprehensive score for extract yield and transfer rates of epicatechin and naringin as an evaluation index,the decoction process was optimized by orthogonal test.With sugarless paste relative density,medicinal powder fineness,sugarless paste-corn starch ratio,drying temperature and drying time as influencing factors,soft material traits,pill formability,moisture and disintegration time limit as evaluation indices,the formability process was optimized by single factor test.TLC was adopted in the qualitative identification of Dipsaci Radix,salt-processed Psoraleae Fructus,cooked Rhei Radix et Rhizoma and Notoginseng Radix et Rhizoma.HPLC was used for the content determination of paeoniflorin and naringin.RESULTS The optimal decoction process was determined to be 0.5 h for decoction time,two times for decoction frequency,and 10 times for water addition,the comprehensive score was 0.93.The optimal formability process was determined to be 1.21-1.22 for sugarless paste relative density,80 mesh for medicinal powder fineness,1∶0.17-1∶0.18 for sugarless paste-corn starch ratio,70 ℃ for drying temperature,and 24 h for drying time,good soft material traits and pill formability were observable,and moisture and disintegration time limit accored with 2020 edition of Chinese Pharmacopoeia requirements.The TLC spots were clear without negative interference.Two constituents showed good linear relationships within 61.30-490.41 μg/mL(r=0.999 8)and 3.27-26.18 μg/mL(r=0.999 8),whose average recoveries were 100.15％and 98.15％with the RSDs of 0.55％and 2.30％,respectively.CONCLUSION This stable,reliable and specific method can be used for the production and quality evaluation of Zhenggu Pills.

AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P＞0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.