Healthy female rabbits aged 3.5 to 4.0 months were randomly divided into four groups:the white light group(control group A),the green light group(treatment group B),the red light group(treatment group C)and the blue light group(treatment group D)with 3 replicates in each group,and 12 rabbits in each replicate.The light intensity was set to 80 lx,and the light was 16 h per day for 6 days before artificial insemination.Three reproductive cycles were carried out to de-termine the reproductive performance of female rabbits under different light colors,such as the number of fetuses,total litter size,weaning litter weight and serum reproductive hormone content.The results showed that,according to the comprehensive statistics of three breeding cycles:(1)the melatonin levels in the green group and red group were significantly lower than those in white group(P＜0.01),and the green group was significantly lower than the blue group(P＜0.05);the levels of luteinizing hormone in green group and red group were significantly higher than those in white group(P＜0.01);the follicle stimulating hormone in the green group was significantly high-er than in white group(P＜0.05);the estradiol content in the green group was significantly higher than that in the white group and blue group(P＜0.01),and significantly higher than that in the red group(P＜0.05).(2)the conception rate of the group was significantly higher than that of the white group(P＜0.01),and significantly higher than that of the red group and blue group(P＜0.05).(3)the number of rabbits in the green group at 30 days of age was significantly higher than that in the red group and the blue group(P＜0.05),and the litter weight at 30 days of age was significantly higher than that in the red group and the blue group(P＜0.01),and significantly higher than that in the white group(P＜0.05).In conclusion,the LED light belt is controlled by a dynamic light control system,the light intensity is set to 80 lx,and the light is 16 h a day for 6 d before artificial insemination.Green light can reduce the serum melatonin of Fujian white rabbits,which has the best comprehensive effect on the same period of conception rate and reproductive performance of Fujian white rabbits.

Objective:To explore the effectiveness and application value of focused ultrasound ablation surgery (FUAS) combined with hysteroscopic surgery in treating solitary type Ⅱ submucosal uterine fibroids with maximum diameter >5 cm.Methods:Clinical data of 35 patients with a single type Ⅱ submucosal uterine fibroid with maximum diameter greater than 5 cm who underwent FUAS combined with hysteroscopic surgery at Qingdao Women and Children′s Hospital from June 2020 to December 2023 were collected. The clinical characteristics, treatments and treatment outcomes were retrospectively analyzed.Results:(1) Clinical characteristics: the mean age of the 35 patients was (36.7±6.6) years, with a median maximum diameter of fibroids of 56 mm (range: 51-80 mm). All patients presented with symptoms of menorrhagia, median menstrual bleeding score was 5 points (ranged from 3 to 5 points), and 34 cases (97.1%, 34/35) had concomitant anemia, the mean hemoglobin was (83.1±13.8) g/L of 35 patients. (2) Treatments: all 35 patients underwent FUAS treatment initially, with a lesion ablation rate ranging from 69.7% to 97.9% (median:90.7%), and no complications occurred. After FUAS treatment, the volume of fibroids decreased in all patients, with a volume reduction rate ranging from 30.57% to 87.22% (median:76.03%). Hysteroscopic surgery was performed 3-14 months (median: 5 months) after FUAS to remove the necrotic fibroid tissue, achieving a 100.0% (35/35) fibroid resection rate. Only 1 patient developed complications of hyperhyderation syndrome during hysteroscopic surgery, and no complications occurred in the remaining patients. (3) Evaluation of efficacy: after FUAS pretreatment, the maximum diameter of fibroids in the 35 patients decreased significantly ( Z=-5.171, P<0.001), as did the volume of fibroids ( Z=-5.159, P<0.001). The hemoglobin level increased significantly compared to the level before FUAS in all cases ( t=-8.657, P<0.001), and median menstrual bleeding score decreased to 2 points (range: 1-3 points), significantly lower than original level ( Z=-5.292, P<0.001). At the 3-month follow-up after hysteroscopic surgery, all patients were free of anemia symptoms, with menstrual bleeding scores totally decreased to 1 point, significantly lower than that before hysteroscopic surgery ( Z=-4.786, P<0.001); hemoglobin level [(118.7±5.6) g/L] significantly increased compared to that before hysteroscopic surgery ( t=-9.258, P<0.001). All patients underwent gynecological transvaginal ultrasound re-examination, which did not reveal any residual fibroids. Conclusion:FUAS combined with hysteroscopic surgery is effective in treating solitary type Ⅱ submucosal uterine fibroids with maximum diameter >5 cm, providing a new treatment option for patients.

Objective:To compare the efficacy, safety, and cost-effectiveness of the trastuzumab originator (HST) versus its biosimilar (HLX02) combined with pertuzumab and chemotherapy as neoadjuvant treatment in patients with HER-2-positive breast cancer.Methods:This retrospective cohort study included 175 patients with HER-2-positive breast cancer who received neoadjuvant therapy followed by curative surgery at the Cancer Hospital Chinese Academy of Medical Sciences between October 2020 and January 2024. Patients were divided into two groups based on the trastuzumab formulation used: the HST group ( n=89) and the HLX02 group ( n=86).The efficacy, safety, and trastuzumab-related treatment costs were compared between the two groups. Moreover, using Logistic regression model to identify the factors influencing total pathological complete response (tpCR) rates. Results:There were statistically significant differences in clinical T stage and surgical approach between the HST and HLX02 groups ( P＜0.05). Other clinicopathological characteristics, such as age and histological grade, showed no statistically significant differences ( P＞0.05), with most baseline characteristics remaining balanced between the two groups. There were no significant differences in tpCR rates ( P=0.957) or Miller-Payne (MP) grading rates ( P=0.991) between the HST and HLX02 groups. The tpCR rates for the two groups were 55.1% (49/89) and 54.7% (47/86), respectively. The rates of achieving grade 5 (G5) in the postoperative MP pathological grading system were 55.1% (49/89) and 55.8% (48/86), respectively, with no statistically significant difference ( P=0.991). Univariate and multivariate Logistic regression analyses showed that hormone receptor status is an independent risk factor affecting tpCR ( OR=0.31, 95% CI; 0.16-0.61, P＜0.001). The incidence of adverse event during neoadjuvant therapy was similar between the groups, with no occurrences of trastuzumab-related cardiac toxicity. The HLX02 regimen showed a lower cost-effectiveness ratio (586.48 vs. 604.96) and reduced trastuzumab treatment costs during neoadjuvant therapy compared to HST [tpCR:(31 208.37±2 191.00) CNY vs. (33 224.49±2 741.00) CNY; non-tpCR: 33 030.05±5 787.00) CNY vs. (33 412.50±4 203.00) CNY, P＜0.05]. Conclusions:In the neoadjuvant treatment of early-stage HER-2-positive breast cancer, HLX02 combined with pertuzumab and chemotherapy demonstrates similar efficacy and safety to the trastuzumab originator, while offering a significant cost advantage.

Objective:To explore the effectiveness and application value of focused ultrasound ablation surgery (FUAS) combined with hysteroscopic surgery in treating solitary type Ⅱ submucosal uterine fibroids with maximum diameter >5 cm.Methods:Clinical data of 35 patients with a single type Ⅱ submucosal uterine fibroid with maximum diameter greater than 5 cm who underwent FUAS combined with hysteroscopic surgery at Qingdao Women and Children′s Hospital from June 2020 to December 2023 were collected. The clinical characteristics, treatments and treatment outcomes were retrospectively analyzed.Results:(1) Clinical characteristics: the mean age of the 35 patients was (36.7±6.6) years, with a median maximum diameter of fibroids of 56 mm (range: 51-80 mm). All patients presented with symptoms of menorrhagia, median menstrual bleeding score was 5 points (ranged from 3 to 5 points), and 34 cases (97.1%, 34/35) had concomitant anemia, the mean hemoglobin was (83.1±13.8) g/L of 35 patients. (2) Treatments: all 35 patients underwent FUAS treatment initially, with a lesion ablation rate ranging from 69.7% to 97.9% (median:90.7%), and no complications occurred. After FUAS treatment, the volume of fibroids decreased in all patients, with a volume reduction rate ranging from 30.57% to 87.22% (median:76.03%). Hysteroscopic surgery was performed 3-14 months (median: 5 months) after FUAS to remove the necrotic fibroid tissue, achieving a 100.0% (35/35) fibroid resection rate. Only 1 patient developed complications of hyperhyderation syndrome during hysteroscopic surgery, and no complications occurred in the remaining patients. (3) Evaluation of efficacy: after FUAS pretreatment, the maximum diameter of fibroids in the 35 patients decreased significantly ( Z=-5.171, P<0.001), as did the volume of fibroids ( Z=-5.159, P<0.001). The hemoglobin level increased significantly compared to the level before FUAS in all cases ( t=-8.657, P<0.001), and median menstrual bleeding score decreased to 2 points (range: 1-3 points), significantly lower than original level ( Z=-5.292, P<0.001). At the 3-month follow-up after hysteroscopic surgery, all patients were free of anemia symptoms, with menstrual bleeding scores totally decreased to 1 point, significantly lower than that before hysteroscopic surgery ( Z=-4.786, P<0.001); hemoglobin level [(118.7±5.6) g/L] significantly increased compared to that before hysteroscopic surgery ( t=-9.258, P<0.001). All patients underwent gynecological transvaginal ultrasound re-examination, which did not reveal any residual fibroids. Conclusion:FUAS combined with hysteroscopic surgery is effective in treating solitary type Ⅱ submucosal uterine fibroids with maximum diameter >5 cm, providing a new treatment option for patients.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Healthy female rabbits aged 3.5 to 4.0 months were randomly divided into four groups:the white light group(control group A),the green light group(treatment group B),the red light group(treatment group C)and the blue light group(treatment group D)with 3 replicates in each group,and 12 rabbits in each replicate.The light intensity was set to 80 lx,and the light was 16 h per day for 6 days before artificial insemination.Three reproductive cycles were carried out to de-termine the reproductive performance of female rabbits under different light colors,such as the number of fetuses,total litter size,weaning litter weight and serum reproductive hormone content.The results showed that,according to the comprehensive statistics of three breeding cycles:(1)the melatonin levels in the green group and red group were significantly lower than those in white group(P＜0.01),and the green group was significantly lower than the blue group(P＜0.05);the levels of luteinizing hormone in green group and red group were significantly higher than those in white group(P＜0.01);the follicle stimulating hormone in the green group was significantly high-er than in white group(P＜0.05);the estradiol content in the green group was significantly higher than that in the white group and blue group(P＜0.01),and significantly higher than that in the red group(P＜0.05).(2)the conception rate of the group was significantly higher than that of the white group(P＜0.01),and significantly higher than that of the red group and blue group(P＜0.05).(3)the number of rabbits in the green group at 30 days of age was significantly higher than that in the red group and the blue group(P＜0.05),and the litter weight at 30 days of age was significantly higher than that in the red group and the blue group(P＜0.01),and significantly higher than that in the white group(P＜0.05).In conclusion,the LED light belt is controlled by a dynamic light control system,the light intensity is set to 80 lx,and the light is 16 h a day for 6 d before artificial insemination.Green light can reduce the serum melatonin of Fujian white rabbits,which has the best comprehensive effect on the same period of conception rate and reproductive performance of Fujian white rabbits.

Objective:To compare the efficacy, safety, and cost-effectiveness of the trastuzumab originator (HST) versus its biosimilar (HLX02) combined with pertuzumab and chemotherapy as neoadjuvant treatment in patients with HER-2-positive breast cancer.Methods:This retrospective cohort study included 175 patients with HER-2-positive breast cancer who received neoadjuvant therapy followed by curative surgery at the Cancer Hospital Chinese Academy of Medical Sciences between October 2020 and January 2024. Patients were divided into two groups based on the trastuzumab formulation used: the HST group ( n=89) and the HLX02 group ( n=86).The efficacy, safety, and trastuzumab-related treatment costs were compared between the two groups. Moreover, using Logistic regression model to identify the factors influencing total pathological complete response (tpCR) rates. Results:There were statistically significant differences in clinical T stage and surgical approach between the HST and HLX02 groups ( P＜0.05). Other clinicopathological characteristics, such as age and histological grade, showed no statistically significant differences ( P＞0.05), with most baseline characteristics remaining balanced between the two groups. There were no significant differences in tpCR rates ( P=0.957) or Miller-Payne (MP) grading rates ( P=0.991) between the HST and HLX02 groups. The tpCR rates for the two groups were 55.1% (49/89) and 54.7% (47/86), respectively. The rates of achieving grade 5 (G5) in the postoperative MP pathological grading system were 55.1% (49/89) and 55.8% (48/86), respectively, with no statistically significant difference ( P=0.991). Univariate and multivariate Logistic regression analyses showed that hormone receptor status is an independent risk factor affecting tpCR ( OR=0.31, 95% CI; 0.16-0.61, P＜0.001). The incidence of adverse event during neoadjuvant therapy was similar between the groups, with no occurrences of trastuzumab-related cardiac toxicity. The HLX02 regimen showed a lower cost-effectiveness ratio (586.48 vs. 604.96) and reduced trastuzumab treatment costs during neoadjuvant therapy compared to HST [tpCR:(31 208.37±2 191.00) CNY vs. (33 224.49±2 741.00) CNY; non-tpCR: 33 030.05±5 787.00) CNY vs. (33 412.50±4 203.00) CNY, P＜0.05]. Conclusions:In the neoadjuvant treatment of early-stage HER-2-positive breast cancer, HLX02 combined with pertuzumab and chemotherapy demonstrates similar efficacy and safety to the trastuzumab originator, while offering a significant cost advantage.

OBJECTIVE To establish the fingerprint of Pinghuo tea standard decoction and a method for determination of multi-component to clarify the transfer relationship of quantities and quality from pieces and standard decoction.METHODS Fifteen batches of Pinghuo tea standard decoction were prepared and the extract rate was determined;the fingerprint of the preparation was established by using high-performance liquid chromatography(HPLC);the similarity evaluation and the determination of common peaks were performed,and chemometric analysis was performed;the same method was used to determine the content of indicator components and the transfer rate was calculated.The chromatographic column was Venusil C18 column with mobile phase consisted of acetonitrile-0.1％ phosphoric acid solution (gradient elution);the column temperature was 30 ℃,and the detection wavelengths were 238 nm (0-37 min,85-102 min) and 330 nm (37-85 min) at a flow rate of 1.0 mL/min with an injection volume of 10 μL.RESULTS The similarity of HPLC fingerprints for 15 batches of Pinghuo tea standard decoction was not lower than 0.968.A total of 24 common peaks were calibrated and 9 peaks were recognized,which were as follows neochlorogenic acid (peak 3),chlorogenic acid (peak 6),geniposide (peak 9),glycyrrhizin (peak 10),galuteolin (peak 11),isochlorogenic acid A (peak 14),luteolin (peak 21),kaempferol (peak 23) and glycyrrhizic acid (peak 24).Cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis showed consistent results,all of which could classify the 15 batches of samples into three categories.The linear range of indicator components in 15 batches of Pinghuo tea standard decoction,such as geniposide,luteolin,isochlorogenic acid A,glycyrrhizin,and glycyrrhizic acid,were 0.020580-0.411600,0.001617-0.080850,0.006076-0.607600,0.005125-0.071740,and 0.017288-0.432200 mg/mL,respectively;RSDs of precision,repeatability,stability and recovery rate tests were all not higher than 4％ (n=6).The mass fractions ranged 3.2279-10.0022,0.2974-0.5546,3.3501-6.1596,0.7206-1.0733,2.0031-3.0301 mg/g;transfer rates from the pieces and standard decoction were 19.7628％-35.8405％,12.1233％-21.2540％,46.0972％-82.8694％,58.7088％-91.6296％,39.1143％-63.7106％.The transfer rates of the extract from 15 batches of Pinghuo tea standard decoction ranged from 61.15％-84.68％.CONCLUSIONS Established HPLC fingerprint and content determination methods in this study are simple and accurate,which can provide reference for the quantitative value transfer study,quality control,clinical application and the development of subsequent formulations of Pinghuo tea standard decoction.

Objective To understand the epidemic characteristics of Norovirus infection in schools in Hefei City,and provide scientific basis for the prevention and control of Norovirus infection in schools.Methods The investiga-tion reports of Norovirus infection reported by the centers for disease control and prevention(CDC)of all counties(cities and districts)in Hefei City and the laboratory test results of Hefei CDC from 2018 to 2022 were analyzed by descriptive epidemiological methods.The related indicators of Norovirus infection,including the attack rate,timeli-ness of reporting,duration of epidemic,clinical symptoms,as well as GⅠ and G Ⅱ classification of Norovirus were compared.Results From 2018 to 2022,there were 217 school Norovirus infections outbreaks in Hefei City,with 3 002 cases and 314 006 affected people.The average annual attack rate ranged from 0.82％to 1.32％.Most cases were from kindergartens,there were 116 cases,accounting for 53.46％,with an average attack rate of 2.87％.The time distribution was bimodal,concentrated in March-June and September-December each year.The attack rate and duration of outbreaks were both significantly higher than those of clustering epidemics(both P＜0.001).Positive correlation existed between the timeliness of reporting and the number of outbreaks at the time of receiving the re-port as well as the duration of the epidemic(r=0.182,0.783,respectively,both P＜0.001).With the advance-ment of the academic stage,the symptom with diarrhea showed an increasing trend(x2trend=743.236,P＜0.001),the symptom with vomiting presented a decreasing trend(x2trend=386.888,P＜0.001),and the symptoms with both diarrhea and vomiting presented an increasing trend(x2trend=327.264,P＜0.001),while the symptom with fe-ver presented a decreasing trend(x2trend=15.717,P＜0.001).The positive detection rate of anal swab specimens(60.10％)was higher than that of vomit and environmental specimens(38.71％,14.29％,respectively,x2=135.685,P＜0.001).The laboratory identified 181 cases with Norovirus GⅠ and G Ⅱ subtypes,including 28 cases of G Ⅰsubtype,accounting for 15.47％,and 149 cases of G Ⅱ subtype,accounting for 82.32％.Conclusion Schools are locations with high incidence of Norovirus infection.At the beginning of the school season,various prevention and control measures should be strictly implemented to improve the monitoring sensitivity of symptoms like vomiting,diarrhea,and so on,so as to achieve early detection,early report and early treatment.

AIM:To examine the predictive perfor-mance of the PPK software JPKD for the steady-state concentrations of amikacin and recommend the applicable conditions under fixed daily dosage of 400 mg and 600 mg.METHODS:Inpatients using amikacin in the First Affiliated Hospital of Bengbu Medical University from July 2022 to February 2024 were enrolled,and the measured concentra-tions of amikacin were detected by LC-MS/MS;Ver-ified the predictive performance of JPKD software for peak and trough concentrations of amikacin;JP-KD software was applied to predict the steady-state concentrations of amikacin in the patients at the infusion time of 0.5,1.0,1.5,2.0,2.5,and 3.0 h,and then compared the variability of steady-state concentrations with different levels of renal function at optimal infusion time,then the C max/MIC values were measured.RESULTS:A total of 69 patients were enrolled,including 18 patients with steady state trough concentrations and 17 patients with steady state peak concentrations.It was found that JPKD had a poor predictive ability for steady state trough concentrations but a good predictive ability for peak concentrations,the WRES＜10％be-tween predictive and measured concentrations,and a strong correlation existed between them(r=0.806).With the shortening infusion time,the high-er peak concentrations.The predicted peak concen-trations at 0.5 h and 1.0 h infusion time groups were(34.81±6.87)μg/mL and(32.51±6.07)μg/mL,respectively.With the decline of the renal function,the peak concentrations showed a increasing trend.On the same level of renal function,the peak concentrations in the 600 mg group was high-er than that of the 400 mg group.When MIC ≤2 μg/mL,400 mg daily dose was chosen;when MIC=4 μg/mL,400 mg daily dose could be used for CKD3b stage patients,and 600 mg daily dose could be used for CKD1,CKD2,and CKD3a stage patients;when MIC=8 μg/mL,it was predicted that a higher dose was needed to achieve the expected target.CONCLUSION:Amikacin is preferably administered intravenously for 0.5 to 1.0 h,fixed daily doses of 400 mg and 600 mg are indicated for some pa-tients according to the target bacterial MIC and re-nal function.