Objective:To establish graded forecast models of pollen concentration in spring and summer-autumn in northern China, based on long-term data of pollen and allergic rhinitis (AR) medical visits in 8 cities of northern China.Methods:Pollen concentration and the characteristics of AR patients from 8 cities of northern China, including Beijing, Baotou, Hohhot, Xi′an, Xining, Cangzhou, Liaocheng and Zibo, were analyzed. Spearman′s correlation was used to examine the relationship between pollen concentration and daily AR patient visits. A pollen concentration grading was establish, and a pollen forecast model was created using the eXtreme gradient boosting (XGBoost) algorithm. The model incorporated meteorological factors and the 3-day moving average of pollen concentrations.Results:The spring pollen period started early and lasted long in Beijing and Xi ′an, while the summer-autumn pollen period started earlier and persisted longer in Xining, Baotou and Hohhot. During summer-autumn pollen period, and the spring period in most cities (except Baotou and Cangzhou), average daily patient visits were significantly higher than those in non-pollen periods. A strong correlation was observed between daily AR patient visits and the 3-day moving average of pollen concentrations in both the spring and summer-autumn periods across all cities. Based on the correlation, a pollen concentration grading standard of northern China was established. The accuracy evaluation of pollen concentration prediction model showed that the percentage of forecasts with either completely accurate or within one level difference exceeded 91% in spring and 95% in summer-autumn. The most important predictive variable in the model was the pollen level from previous day, followed by the temperature and humidity.Conclusion:The grading prediction model for pollen concentration provides guidance for AR patients in term of travel, early defense and treatment, as well as the determining medication schedules for clinical drug research and specific immunotherapy.

Objective:To investigate the impact of para-tumoral micro-metastasis(PTMM) and other clinicopathological characteristics on the prognosis of patients with intrahepatic cholangiocarcinoma (ICC).Methods:This is a retrospective cohort study. Clinical data from 137 ICC patients who underwent radical resection at the Hepatobiliary Surgery Center, Department of General Surgery, Huashan Hospital, Fudan University, between January 2017 and December 2022 were analyzed retrospectively. The cohort included 91 males and 46 females, with age ( M(IQR)) of 63 (13) years (range: 32 to 82 years). Kaplan-Meier curves were used to estimate median survival times, while Log-rank tests assessed differences in overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate Cox regression models were employed to identify factors associated with OS and RFS. Results:The median OS for all 137 ICC patients was 34 months, with 1-, 2-, and 3-year OS rates of 90.7%, 69.4%, and 39.5%, respectively. The results of univariate and multivariate Cox analysis showed that Child-Pugh grade, CA19-9, carcinoembryonic antigen, and PTMM were independent prognostic factors for OS in ICC patients after radical resection (all P<0.05), Child-Pugh grade, maximum tumor diameter, whether lymph node metastasis, and PTMM were independent prognostic factors for RFS in radical resection in ICC patients (all P<0.05). PTMM-positive patients had a median OS of 21 months and median RFS of 12 months, whereas PTMM-negative patients exhibited a median OS exceeding 60 months and median RFS of 36 months. Log-rank tests demonstrated statistically significant differences in OS and RFS between PTMM-positive and PTMM-negative patients ( P<0.01 and P=0.001, respectively). Conclusion:Preliminary findings suggest that PTMM holds significant prognostic value in evaluating outcomes for ICC patients undergoing curative resection.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To establish graded forecast models of pollen concentration in spring and summer-autumn in northern China, based on long-term data of pollen and allergic rhinitis (AR) medical visits in 8 cities of northern China.Methods:Pollen concentration and the characteristics of AR patients from 8 cities of northern China, including Beijing, Baotou, Hohhot, Xi′an, Xining, Cangzhou, Liaocheng and Zibo, were analyzed. Spearman′s correlation was used to examine the relationship between pollen concentration and daily AR patient visits. A pollen concentration grading was establish, and a pollen forecast model was created using the eXtreme gradient boosting (XGBoost) algorithm. The model incorporated meteorological factors and the 3-day moving average of pollen concentrations.Results:The spring pollen period started early and lasted long in Beijing and Xi ′an, while the summer-autumn pollen period started earlier and persisted longer in Xining, Baotou and Hohhot. During summer-autumn pollen period, and the spring period in most cities (except Baotou and Cangzhou), average daily patient visits were significantly higher than those in non-pollen periods. A strong correlation was observed between daily AR patient visits and the 3-day moving average of pollen concentrations in both the spring and summer-autumn periods across all cities. Based on the correlation, a pollen concentration grading standard of northern China was established. The accuracy evaluation of pollen concentration prediction model showed that the percentage of forecasts with either completely accurate or within one level difference exceeded 91% in spring and 95% in summer-autumn. The most important predictive variable in the model was the pollen level from previous day, followed by the temperature and humidity.Conclusion:The grading prediction model for pollen concentration provides guidance for AR patients in term of travel, early defense and treatment, as well as the determining medication schedules for clinical drug research and specific immunotherapy.

Objective:To investigate the impact of para-tumoral micro-metastasis(PTMM) and other clinicopathological characteristics on the prognosis of patients with intrahepatic cholangiocarcinoma (ICC).Methods:This is a retrospective cohort study. Clinical data from 137 ICC patients who underwent radical resection at the Hepatobiliary Surgery Center, Department of General Surgery, Huashan Hospital, Fudan University, between January 2017 and December 2022 were analyzed retrospectively. The cohort included 91 males and 46 females, with age ( M(IQR)) of 63 (13) years (range: 32 to 82 years). Kaplan-Meier curves were used to estimate median survival times, while Log-rank tests assessed differences in overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate Cox regression models were employed to identify factors associated with OS and RFS. Results:The median OS for all 137 ICC patients was 34 months, with 1-, 2-, and 3-year OS rates of 90.7%, 69.4%, and 39.5%, respectively. The results of univariate and multivariate Cox analysis showed that Child-Pugh grade, CA19-9, carcinoembryonic antigen, and PTMM were independent prognostic factors for OS in ICC patients after radical resection (all P<0.05), Child-Pugh grade, maximum tumor diameter, whether lymph node metastasis, and PTMM were independent prognostic factors for RFS in radical resection in ICC patients (all P<0.05). PTMM-positive patients had a median OS of 21 months and median RFS of 12 months, whereas PTMM-negative patients exhibited a median OS exceeding 60 months and median RFS of 36 months. Log-rank tests demonstrated statistically significant differences in OS and RFS between PTMM-positive and PTMM-negative patients ( P<0.01 and P=0.001, respectively). Conclusion:Preliminary findings suggest that PTMM holds significant prognostic value in evaluating outcomes for ICC patients undergoing curative resection.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To investigate the clinical effectiveness of anastomosis fixation method of lifting the suborbicularis oculi fat (SOOF) and fixing with the orbital septum and fat to correct eyelid bags with tear trough deformity.Methods:A retrospective analysis was conducted on patients treated at Hunan Provincial People’s Hospital (the First Affiliated Hospital of Hunan Normal University) from January 2019 to January 2021. The patients underwent lower eyelid blepharoplasty via a sub-lower eyelid skin approach. During the surgery, the SOOF was lifted and fixed with the orbital septum and fat, correcting the eye bags, filling the tear troughs, and lifting the midface. Postoperative observations included incision healing and complications. The correction of eye bags, tear troughs, and midface sagging was followed up. Adobe Photoshop CS6 software was used to measure the vertical distance from the nasolabial and buccal fat prominent point to the lower eyelid margin before surgery and at the last follow-up to evaluate the correction of midface sagging. Data were expressed as Mean ± SD, and pre- and post-operative comparisons were analyzed using paired t-test, with P<0.05 indicating statistical significance. Patients’ and nurses’ satisfaction evaluations of surgical outcomes were classified into three levels: satisfied, basically satisfied, and dissatisfied, requiring consensus between the two evaluators. Results:A total of 132 patients (264 eyes) were included, consisting of 23 males and 109 females, with an average age of (50.3±6.0) years. Hirmand tear trough classification included 178 type Ⅱeyes and 86 type Ⅲ eyes. Postoperative wound healing was well, with no hematoma, infection, diplopia, corneal foreign body sensation, and discomfort from external eye corner tightness. Follow-up ranged from 6-12 months, with 252 out of 264 eye bags disappeared and 12 eye bags reduced. Among the 86 type Ⅲ tear trough eyes, 10 improved to type Ⅰ, while the remaining 76 type Ⅲ and 178 type Ⅱ tear troughs disappeared postoperatively. All 264 midface sagging cases showed improvement, with the vertical distance from the nasolabial fat prominence point to the lower eyelid margin significantly shortening postoperatively [(29.23±1.58) mm vs. (34.08±3.23) mm, t=22.88, P<0.001)]. Satisfaction evaluation result showed 118 cases were satisfied (satisfaction rate of 89.4%), and 14 cases were basically satisfied. Conclusion:The anastomosis fixation method of lifting the SOOF and fixing with the orbital septum and fat effectively removes eyelid bags, smooths tear troughs, and lifts the midface, achieving a rejuvenated appearance and renders a high patient satisfaction rate.

Objective:To investigate the clinical effectiveness of anastomosis fixation method of lifting the suborbicularis oculi fat (SOOF) and fixing with the orbital septum and fat to correct eyelid bags with tear trough deformity.Methods:A retrospective analysis was conducted on patients treated at Hunan Provincial People’s Hospital (the First Affiliated Hospital of Hunan Normal University) from January 2019 to January 2021. The patients underwent lower eyelid blepharoplasty via a sub-lower eyelid skin approach. During the surgery, the SOOF was lifted and fixed with the orbital septum and fat, correcting the eye bags, filling the tear troughs, and lifting the midface. Postoperative observations included incision healing and complications. The correction of eye bags, tear troughs, and midface sagging was followed up. Adobe Photoshop CS6 software was used to measure the vertical distance from the nasolabial and buccal fat prominent point to the lower eyelid margin before surgery and at the last follow-up to evaluate the correction of midface sagging. Data were expressed as Mean ± SD, and pre- and post-operative comparisons were analyzed using paired t-test, with P<0.05 indicating statistical significance. Patients’ and nurses’ satisfaction evaluations of surgical outcomes were classified into three levels: satisfied, basically satisfied, and dissatisfied, requiring consensus between the two evaluators. Results:A total of 132 patients (264 eyes) were included, consisting of 23 males and 109 females, with an average age of (50.3±6.0) years. Hirmand tear trough classification included 178 type Ⅱeyes and 86 type Ⅲ eyes. Postoperative wound healing was well, with no hematoma, infection, diplopia, corneal foreign body sensation, and discomfort from external eye corner tightness. Follow-up ranged from 6-12 months, with 252 out of 264 eye bags disappeared and 12 eye bags reduced. Among the 86 type Ⅲ tear trough eyes, 10 improved to type Ⅰ, while the remaining 76 type Ⅲ and 178 type Ⅱ tear troughs disappeared postoperatively. All 264 midface sagging cases showed improvement, with the vertical distance from the nasolabial fat prominence point to the lower eyelid margin significantly shortening postoperatively [(29.23±1.58) mm vs. (34.08±3.23) mm, t=22.88, P<0.001)]. Satisfaction evaluation result showed 118 cases were satisfied (satisfaction rate of 89.4%), and 14 cases were basically satisfied. Conclusion:The anastomosis fixation method of lifting the SOOF and fixing with the orbital septum and fat effectively removes eyelid bags, smooths tear troughs, and lifts the midface, achieving a rejuvenated appearance and renders a high patient satisfaction rate.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective:To investigate the prevalence of drinking-tea fluorosis from 2016 to 2018 in Lhasa City, Tibet, and to provide clues and basic data for preventing this disease.Methods:According to the stratified cluster sampling method, Mozhugongka County and Nimu County in 2016, Dazi District in 2017, Chengguan District, Duilongdeqing District and Qushui County of Lhasa City in 2018 were selected as survey counties (districts), each county (district) selected 1 township (town) according to the 5 directions of east, south, west, north, and middle, and each township (town) selected 1 to 2 administrative villages as survey points, and each survey point recruited villager volunteers aged ≥18 years for survey subject. All volunteers were tested for dental fluorosis (Dean method) and skeletal fluorosis (X-ray), and samples of drinking water, brick tea consumed at home and residents' urine were collected for water fluoride, tea fluoride, and urine fluoride testing.Results:A total of 30 water samples were collected, and the water fluoride content was all < 1.0 mg/L. The average fluorine content was 1 167.5 mg/kg among 314 samples of brick tea investigated in this study. The qualification rate of brick tea in each survey county was 0 - 16.7%. The daily intake of fluoride in brick tea per person was 6.4 mg. The prevalence of dental fluorosis was 18.1% (350/1 929) among all enrolled participants, 4 of the 6 survey counties (districts) had varying degrees of dental fluorosis. A total of 1 637 urine samples were collected and detected, and the urine fluorine level ranged from 0.01 to 11.01 mg/L, with a geometric mean of 1.07 mg/L. The urine fluorine levels in all investigated counties (districts) were under the standard limits (≤1.6 mg/L). Eight adults were diagnosed with skeletal fluorosis of degree Ⅰ via X-ray detection, with a detection rate of 0.4% (8/1 929). Totally 20.2% (390/1 929) of people reported suffered from two or more joint disease. Furthermore, 6 counties (districts) in Lhasa City were identified as mild drinking-tea type endemic fluorosis disease areas.Conclusion:From 2016 to 2018, the fluorine content of brick tea in Lhasa has exceeded the standard seriously, dental fluorosis is mildly prevalent in some counties (districts), and 6 counties (districts) are all mild tea-drinking fluorosis areas.