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 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 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 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 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 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.

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

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.

Objective:To explore the block-based charging method for centralized dispensing of neonatal drugs in pharmacy intravenous admixture service (PIVAS), analyze its effect on drug savings and inpatient drug cost, so as to provide the reference for the appropriate charging method of neonatal drugs.Methods:According to the balance quantity and amount of neonatal intravenous drugs that were centrally allocated by the PIVAS of our hospital, refer to the doctor′s orders, the dosage per dose as well as the number of patients per dose were analyzed, then the drug types and plans for block-based charging were formulated. Before and after the implementation of the plan, the monthly average drug balance quantity and amount, the average number of drug charges for the neonates, the average daily drug cost, and the adverse events of related drugs were used as the indicators to be investigated to clarify the implementation effect of the block-based charging mothod.Results:Fourteen medicines were charged by block-based, including 4 antibiotics, 2 ordinary infusion preparations, and 8 parenteral nutrition solution preparations. The monthly average drug balance quantity was reduced from 5 047±541 to 1 856±225, and the monthly average balance amount was reduced from 65 811±10 265 yuan to 20 659±6 002 yuan. The average drug dosage for children in the trial drug was significantly reduced with a decrease range of 39.2% to 90.1%. Both the inpatient daily drug cost of neonatus and the daily average antibacterial drug cost was decreased. During the centralized dispensing of neonatal drugs, no related adverse drug events occurred.Conclusions:The block-based charging method of centralized drug distribution can improve the utilization rate of drugs, reduce drug waste, reduce the cost of inpatient medicines the financial burden on children′s families, which is worthy of further promotion and implementation.