Objective To observe the effects of electroacupuncture at"Neiguan"and"Gongsun"on autophagy and apoptosis related indexes of interstitial cells of Cajal(ICC)in rats with functional dyspepsia(FD);To explore its possible mechanism on improving gastrointestinal motility of FD.Methods Totally 32 SPF grade SD rats were randomly divided into blank group,model group,electroacupuncture group and Western medicine group,with 8 rats in each group.An FD model was constructed using a composite etiology modeling method.The electroacupuncture group received electroacupuncture at"Neiguan"and"Gongsun",while the Western medicine group received oral administration of mosapride once a day for 7 consecutive days.The general condition,body mass and average daily intake of rats were observed every week,and gastric emptying rate and small intestine propulsion rate were detected,transmission electron microscopy was used to observe the structure of gastric antrum ICC,Western blot was used to observe the expressions of c-kit,Beclin1,LC3Ⅱ/Ⅰ,p62,Caspase-3 protein in gastric antrum tissue,qPCR was used to observe the mRNA expressions of Beclin1,LC3Ⅱ/Ⅰ,p62 and c-kit in gastric antrum tissue,TUNEL staining was used to detect the apoptosis rate of cells in gastric antrum tissue.Results Compared with the blank group,the model group rats were mentally lethargic,clustered and curled up,with reduced activity,rough and dull hair,loose and unformed feces,reduced body mass and daily food intake(P<0.05),and gastric emptying rate and small intestine propulsion rate decreased(P<0.01),ICC mitochondria swelled and dissolved,with varying degrees of vacuolar formation,rough endoplasmic reticulum dilation and destruction,and a large number of autophagosomes,the expressions of Beclin1 and LC3 Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue increased(P<0.01),the expressions of p62,c-kit protein and mRNA decreased(P<0.01),while Caspase-3 protein expression increased(P<0.01),and the apoptosis rate of gastric antral tissue cells increased(P<0.01).Compared with the model group,the condition of rats in electroacupuncture group and the Western medicine group were improved,with increased responsiveness,increased mobility,neat hair,formed feces,increased body mass and daily food intake(P<0.01),and gastric emptying rate and small intestine propulsion rate increase(P<0.01),a normal ICC structure,and a small amount of autophagosomes were still visible,the expressions of Beclin1,LC3Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue decreased(P<0.01),the expressions of p62,c-kit protein and mRNA increased(P<0.01),while Caspase-3 protein expression decreased(P<0.01),and the apoptosis rate of gastric antral tissue cells decreased(P<0.01).There was no statistically significant difference in various indicators between electroacupuncture group and Western medicine group(P>0.05).Conclusion Electroacupuncture at"Neiguan"and"Gongsun"can restore the number and structure of ICC and improve gastrointestinal motility,and its mechanism may be related to the inhibition of autophagy and apoptosis levels.

Objective:To investigate the correlation of epithelial lesions among different biopsy sites in the female lower genital tract and the relationship between age and lesion distribution.Methods:A total of 406 148 patients with cervical biopsy specimens archived at the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University from January 2010 to December 2021 were analyzed. Among them, 70 309 cases (17.31%) had concurrent vaginal biopsies, and 16 073 cases (3.96%) had concurrent vulvar biopsies. (1) Cases were divided into four 3-year intervals to compare vaginal or vulvar biopsy rates and high-grade squamous intraepithelial lesion (HSIL) or worse (HSIL +) detection rates across time periods. (2) Correlations between cervical lesions and vaginal or vulvar lesions were assessed. (3) Patients were stratified into three age groups (<30, 30-49, and ≥50 years) to compare vaginal or vulvar HSIL + detection rates. Results:Mean ages of patients with cervical, vaginal, and vulvar biopsies were (41.3±11.0), (47.4±12.5), and (41.9±13.2) years, respectively. Patients with vaginal biopsy were significantly older than cervical or vulvar groups (all P<0.001). (1) Vaginal biopsy rates increased markedly from 7.37% (2010—2012) to 22.76% (2019—2021; χ2=9 205.01, P<0.001); vulvar biopsy rates increased slightly from 2.80% to 5.69% ( χ2=1 777.25, P<0.001). Correspondingly, vaginal HSIL + detection rates rose from 0.28% to >0.5% (0.56% in 2013—2015, 0.59% in 2016—2018, 0.51% in 2019—2021; χ2=134.70, P<0.001), while vulvar HSIL + rates increased from 0.03% to 0.33% ( χ2=56.54, P<0.001). (2) Weak correlation existed between cervical and vaginal lesions ( r=0.28; P<0.001; n=70 309), while cervical-vulvar correlation was weaker ( r=0.22, P<0.001; n=16 073). (3) Vaginal HSIL + detection rates were higher in cervical HSIL + patients aged 30-49 years (26.65%) and ≥50 years (26.79%) versus <30 years (14.63%; both P<0.001). Conversely, vulvar HSIL + detection rates were higher in the <30 years group (23.08%) versus 30-49 years (13.83%) and ≥50 years (12.89%; both P<0.05). Conclusions:Vaginal or vulvar lesion detection rates increase with biopsy frequency. Vaginal lesions correlate with cervical abnormalities, whereas vulvar lesions are relatively independent. In cervical HSIL + patients, those <30 years are more prone to have vulvar HSIL +, while those ≥30 years show higher vaginal HSIL + incidence. These age-specific distribution patterns inform optimized biopsy strategies.

Objective To explore method for improving the colonization efficiency of Helicobacter pylori(Hp)in the mouse stomach and to determine if the proton pump inhibitor(PPI)pantoprazole can act as a colonization adjuvant to enhance Hp colonization,with the aim of providing an effective tool for establishing an Hp infection mouse model.Methods The Hp Sydney strain 1(SS1)was introduced and solid plate and liquid culture systems were established.The effects of different doses of pantoprazole on gastric acid secretion in mice were compared.The impact of Hp inoculation,alone or combined with pantoprazole pretreatment,on Hp colonization efficiency was analyzed using rapid urease tests,bacterial plate cultures,and TaqMan quantitative polymerase chain reaction.Results PPI pretreatment inhibited gastric acid secretion and promoted Hp colonization in the mouse stomach,to some extent.Conclusions PPI can serve as colonization adjuvants to enhanc e the efficiency of constructing Hp infection mouse models.

Objective To observe the effects of electroacupuncture at"Neiguan"and"Gongsun"on autophagy and apoptosis related indexes of interstitial cells of Cajal(ICC)in rats with functional dyspepsia(FD);To explore its possible mechanism on improving gastrointestinal motility of FD.Methods Totally 32 SPF grade SD rats were randomly divided into blank group,model group,electroacupuncture group and Western medicine group,with 8 rats in each group.An FD model was constructed using a composite etiology modeling method.The electroacupuncture group received electroacupuncture at"Neiguan"and"Gongsun",while the Western medicine group received oral administration of mosapride once a day for 7 consecutive days.The general condition,body mass and average daily intake of rats were observed every week,and gastric emptying rate and small intestine propulsion rate were detected,transmission electron microscopy was used to observe the structure of gastric antrum ICC,Western blot was used to observe the expressions of c-kit,Beclin1,LC3Ⅱ/Ⅰ,p62,Caspase-3 protein in gastric antrum tissue,qPCR was used to observe the mRNA expressions of Beclin1,LC3Ⅱ/Ⅰ,p62 and c-kit in gastric antrum tissue,TUNEL staining was used to detect the apoptosis rate of cells in gastric antrum tissue.Results Compared with the blank group,the model group rats were mentally lethargic,clustered and curled up,with reduced activity,rough and dull hair,loose and unformed feces,reduced body mass and daily food intake(P<0.05),and gastric emptying rate and small intestine propulsion rate decreased(P<0.01),ICC mitochondria swelled and dissolved,with varying degrees of vacuolar formation,rough endoplasmic reticulum dilation and destruction,and a large number of autophagosomes,the expressions of Beclin1 and LC3 Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue increased(P<0.01),the expressions of p62,c-kit protein and mRNA decreased(P<0.01),while Caspase-3 protein expression increased(P<0.01),and the apoptosis rate of gastric antral tissue cells increased(P<0.01).Compared with the model group,the condition of rats in electroacupuncture group and the Western medicine group were improved,with increased responsiveness,increased mobility,neat hair,formed feces,increased body mass and daily food intake(P<0.01),and gastric emptying rate and small intestine propulsion rate increase(P<0.01),a normal ICC structure,and a small amount of autophagosomes were still visible,the expressions of Beclin1,LC3Ⅱ/Ⅰ protein and mRNA in gastric antrum tissue decreased(P<0.01),the expressions of p62,c-kit protein and mRNA increased(P<0.01),while Caspase-3 protein expression decreased(P<0.01),and the apoptosis rate of gastric antral tissue cells decreased(P<0.01).There was no statistically significant difference in various indicators between electroacupuncture group and Western medicine group(P>0.05).Conclusion Electroacupuncture at"Neiguan"and"Gongsun"can restore the number and structure of ICC and improve gastrointestinal motility,and its mechanism may be related to the inhibition of autophagy and apoptosis levels.

Objective To explore method for improving the colonization efficiency of Helicobacter pylori(Hp)in the mouse stomach and to determine if the proton pump inhibitor(PPI)pantoprazole can act as a colonization adjuvant to enhance Hp colonization,with the aim of providing an effective tool for establishing an Hp infection mouse model.Methods The Hp Sydney strain 1(SS1)was introduced and solid plate and liquid culture systems were established.The effects of different doses of pantoprazole on gastric acid secretion in mice were compared.The impact of Hp inoculation,alone or combined with pantoprazole pretreatment,on Hp colonization efficiency was analyzed using rapid urease tests,bacterial plate cultures,and TaqMan quantitative polymerase chain reaction.Results PPI pretreatment inhibited gastric acid secretion and promoted Hp colonization in the mouse stomach,to some extent.Conclusions PPI can serve as colonization adjuvants to enhanc e the efficiency of constructing Hp infection mouse models.

Objective:To investigate the correlation of epithelial lesions among different biopsy sites in the female lower genital tract and the relationship between age and lesion distribution.Methods:A total of 406 148 patients with cervical biopsy specimens archived at the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University from January 2010 to December 2021 were analyzed. Among them, 70 309 cases (17.31%) had concurrent vaginal biopsies, and 16 073 cases (3.96%) had concurrent vulvar biopsies. (1) Cases were divided into four 3-year intervals to compare vaginal or vulvar biopsy rates and high-grade squamous intraepithelial lesion (HSIL) or worse (HSIL +) detection rates across time periods. (2) Correlations between cervical lesions and vaginal or vulvar lesions were assessed. (3) Patients were stratified into three age groups (<30, 30-49, and ≥50 years) to compare vaginal or vulvar HSIL + detection rates. Results:Mean ages of patients with cervical, vaginal, and vulvar biopsies were (41.3±11.0), (47.4±12.5), and (41.9±13.2) years, respectively. Patients with vaginal biopsy were significantly older than cervical or vulvar groups (all P<0.001). (1) Vaginal biopsy rates increased markedly from 7.37% (2010—2012) to 22.76% (2019—2021; χ2=9 205.01, P<0.001); vulvar biopsy rates increased slightly from 2.80% to 5.69% ( χ2=1 777.25, P<0.001). Correspondingly, vaginal HSIL + detection rates rose from 0.28% to >0.5% (0.56% in 2013—2015, 0.59% in 2016—2018, 0.51% in 2019—2021; χ2=134.70, P<0.001), while vulvar HSIL + rates increased from 0.03% to 0.33% ( χ2=56.54, P<0.001). (2) Weak correlation existed between cervical and vaginal lesions ( r=0.28; P<0.001; n=70 309), while cervical-vulvar correlation was weaker ( r=0.22, P<0.001; n=16 073). (3) Vaginal HSIL + detection rates were higher in cervical HSIL + patients aged 30-49 years (26.65%) and ≥50 years (26.79%) versus <30 years (14.63%; both P<0.001). Conversely, vulvar HSIL + detection rates were higher in the <30 years group (23.08%) versus 30-49 years (13.83%) and ≥50 years (12.89%; both P<0.05). Conclusions:Vaginal or vulvar lesion detection rates increase with biopsy frequency. Vaginal lesions correlate with cervical abnormalities, whereas vulvar lesions are relatively independent. In cervical HSIL + patients, those <30 years are more prone to have vulvar HSIL +, while those ≥30 years show higher vaginal HSIL + incidence. These age-specific distribution patterns inform optimized biopsy strategies.

OBJECTIVE To provide reference for the construction of remote inspection mode of pharmaceutical production in China. METHODS By combing the guidance documents of remote inspection and related pilots issued abroad， the experience of constructing remote inspection mode of pharmaceutical production was summarized. RESULTS & CONCLUSIONS Typical foreign countries and regions have carried out remote inspection pilots all over the world， and clearly defined the application situation， implementation process， inspection techniques and related points for attention of remote inspection of pharmaceutical production. In terms of application， the European Union pointed out four specific applicable situations， including travel restrictions， while the United States stipulated that remote inspection was applicable to pre-approved inspection and so on. In terms of the implementation process， the United States developed a four-step method of remote inspection， while the European Union has defined the specific implementation process of remote inspection in more detail. In comparison， Japan paid more attention to the remote inspection process of production documents. In terms of inspection techniques， the European Union used 360° cameras， Matterport 3D technology and document review software to realize the remote inspection of production sites and production documents. In terms of attention points for remote inspection， the United States required that access rights should be set for information sharing to avoid information disclosure. Both the European Union and the United States required inspectors to be trained and equipment inspected before remote inspection. It is suggested that China should formulate unified guidelines for remote inspection of pharmaceutical production， clarify the applicable situations， and formulate the implementation process of remote inspection of pharmaceutical production with reference to the opinions of drug manufacturers. In addition， intelligent remote inspection technology can be used in combination with the information construction level of drug manufacturers， and remote inspection training program can be formulated to cultivate professional remote inspection team.

Objective To make a system evaluation regarding the effect and safety of the"Nourishing Kidney and Activating Blood"method in the treatment of diabetic cognitive impairment.Methods According to the requirements of evidence-based medicine,the domestic and foreign databases were searched comprehensively,and the time limit was from the establishment of databases to June 2022,so as to find out the clinical randomized controlled trials of"Nourishing Kidney and Activating Blood"method in treating diabetic cognitive impairment.Revman5.3 was used for meta-analysis and risk bias evaluation,TSA0.9 for sequential analysis,Stata15.0 for publication bias evaluation,and GRADE3.6 for evidence quality evaluation.Results Eventually,14 RCTs were included with a sample size of 1126 cases.Meta-analysis showed that compared with conventional western medicine treatment,the"Nourishing Kidney and Activating Blood"method could significantly improve the effective rate of treating cognitive dysfunction in diabetes[OR=5.06,95%CI(3.38,7.57),P<0.00001],and significantly improve the total MoCA score of patients[MD=2.11,95%CI(1.76,2.47),P<0.00001],MMSE score[MD=1.86,95%CI(1.13,2.59),P<0.00001],MQ score[MD=13.40,95%CI(11.23,15.57),P<0.00001]and HDS score[MD=-3.36,95%CI(2.61,4.11),P<0.00001].Meanwhile,the"Nourishing Kidney and Activating Blood"method could reduce the level of glycosylated hemoglobin in DCI patients[MD=-0.84,95%CI(-1.37,-0.32),P=0.002].However,since the drugs used in the control group have no hypoglycemic effect,this conclusion needs to be further verified.In addition,the ability of the"Nourishing Kidney and Activating Blood"method to improve CDR score[MD=-0.01,95%CI(-0.08,0.07),P=0.84],ADL score[MD=2.10,95%CI(-1.62,5.82),P=0.27],TCM syndrome score[MD=-4.46,95%CI(-10.94,2.02),P=0.18]and reduce adverse reactions[OR=0.36,95%CI(0.08,1.60),P=0.18]was equivalent to that of conventional western medicine.Begg's test and Egger's test suggested that there might be some publication bias in the research.Metaninf command chart and sequential analysis of experiments indicated that the stability of research results was relatively good.The quality evaluation of evidence showed that the evidence of effective rate,glycosylated hemoglobin,MoCA scale score,MMSE score and MQ score was medium quality,the evidence of fasting blood glucose,CDR score and HDS score was low quality,and the evidence of ADL score,TCM syndrome score and adverse reactions was extremely low quality.Conclusion The existing literature evidence showed that the"Nourishing Kidney and Activating Blood"method had a good clinical effect in treating diabetic cognitive impairment,and it could reduce the blood glucose level and improve the cognitive function of patients,with certain safety.However,the above conclusions still needed more large samples and multi-center RCT to be further verified due to the limitation of the quality and quantity of the included literature.

Early weaned piglets suffer from oxidative stress and enteral infection, which usually results in gut microbial dysbiosis, serve diarrhea, and even death. Rice bran oil (RBO), a polyphenol-enriched by-product of rice processing, has been shown to have antioxidant and anti-inflammatory properties both in vivo and in vitro. Here, we ascertained the proper RBO supplementation level, and subsequently determined its effects on lipopolysaccharide (LPS)-induced intestinal dysfunction in weaned piglets. A total of 168 piglets were randomly allocated into four groups of seven replicates (42 piglets each group, (21±1) d of age, body weight (7.60±0.04) kg, and half males and half females) and were given basal diet (Ctrl) or basal diet supplemented with 0.01% (mass fraction) RBO (RBO1), 0.02% RBO (RBO2), or 0.03% RBO (RBO3) for 21 d. Then, seven piglets from the Ctrl and the RBO were treated with LPS (100 μg/kg body weight (BW)) as LPS group and RBO+LPS group, respectively. Meanwhile, seven piglets from the Ctrl were treated with the saline vehicle (Ctrl group). Four hours later, all treated piglets were sacrificed for taking samples of plasma, jejunum tissues, and feces. The results showed that 0.02% was the optimal dose of dietary RBO supplementation based on diarrhea, average daily gain, and average daily feed intake indices in early weaning piglets. Furthermore, RBO protected piglets against LPS-induced jejunal epithelium damage, which was indicated by the increases in villus height, villus height/crypt depth ratio, and Claudin-1 levels, as well as a decreased level of jejunal epithelium apoptosis. RBO also improved the antioxidant ability of LPS-challenged piglets, which was indicated by the elevated concentrations of catalase and superoxide dismutase, and increased total antioxidant capacity, as well as the decreased concentrations of diamine oxidase and malondialdehyde in plasma. Meanwhile, RBO improved the immune function of LPS-challenged weaned piglets, which was indicated by elevated immunoglobulin A (IgA), IgM, β‍‍-defensin-1, and lysozyme levels in the plasma. In addition, RBO supplementation improved the LPS challenge-induced dysbiosis of gut microbiota. Particularly, the indices of antioxidant capacity, intestinal damage, and immunity were significantly associated with the RBO-regulated gut microbiota. These findings suggested that 0.02% RBO is a suitable dose to protect against LPS-induced intestinal damage, oxidative stress, and jejunal microbiota dysbiosis in early weaned piglets.
Male ; Female ; Swine ; Animals ; Lipopolysaccharides/toxicity* ; Antioxidants/pharmacology* ; Rice Bran Oil ; Dysbiosis ; Dietary Supplements ; Diarrhea/veterinary* ; Weaning ; Body Weight

Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.
Animals ; Alzheimer Disease/metabolism* ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/metabolism* ; Drosophila/physiology* ; Drosophila Proteins/metabolism* ; Resveratrol/pharmacology* ; Sirtuin 1 ; Sleep