1. Development of a method for determination of osmotic pump controlled-release tablets of lorcaserin hydrochloride in beagle dog plasma and its application to pharmacokinetic study
Miao-Miao ZHANG ; Cheng-Jun JIANG ; Chong-Yang WANG ; Ting-Yu GE ; Qi-Qi SONG ; Zhen-Bao LI ; Dian-Lei WANG
Chinese Pharmacological Bulletin 2023;39(5):993-997
Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.
3.Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study.
Yuan Yue ZHU ; Rui Zhi ZHENG ; Gui Xia WANG ; Li CHEN ; Li Xin SHI ; Qing SU ; Min XU ; Yu XU ; Yu Hong CHEN ; Xue Feng YU ; Li YAN ; Tian Ge WANG ; Zhi Yun ZHAO ; Gui Jun QIN ; Qin WAN ; Gang CHEN ; Zheng Nan GAO ; Fei Xia SHEN ; Zuo Jie LUO ; Ying Fen QIN ; Ya Nan HUO ; Qiang LI ; Zhen YE ; Yin Fei ZHANG ; Chao LIU ; You Min WANG ; Sheng Li WU ; Tao YANG ; Hua Cong DENG ; Jia Jun ZHAO ; Lu Lu CHEN ; Yi Ming MU ; Xu Lei TANG ; Ru Ying HU ; Wei Qing WANG ; Guang NING ; Mian LI ; Jie Li LU ; Yu Fang BI
Biomedical and Environmental Sciences 2021;34(1):9-18
Objective:
The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.
Methods:
The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.
Results:
A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).
Conclusion
An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged
;
Asian Continental Ancestry Group
;
Blood Glucose/analysis*
;
China/epidemiology*
;
Cohort Studies
;
Diabetes Mellitus/blood*
;
Female
;
Glucose Tolerance Test
;
Glycated Hemoglobin A/analysis*
;
Glycemic Index
;
Humans
;
Male
;
Middle Aged
;
Uric Acid/blood*
4.Application analysis of a modified retroauricular hairline incision in the resection of a benign parotid gland tumor.
Fen CHEN ; Yu LI ; Xing KE ; Ping-Fan WU ; Ling-Yan GUO ; Zhen-Ge LEI ; Wei-Bin TAN ; Lin-Lin CHEN
West China Journal of Stomatology 2021;39(3):293-299
OBJECTIVES:
This study aimed to evaluate the application value of a modified retroauricular hairline incision and a sternocleidomastoid flap with an inferior pedicle in the resection of benign parotid gland tumors.
METHODS:
Forty-eight patients with benign parotid gland tumors were retrospectively analyzed: 19 cases were included in the experimental group with an improved retroauricular hairline incision and a sternocleidomastoid flap with an inferior pedicle, and 29 cases were assigned in the control group with a modified facelift incision. Operation time, postoperative drainage, postoperative esthetic degree, and incidence of facial nerve paralysis, salivary fistula, and Frey's syndrome were compared.
RESULTS:
After the esthetic procedure, the average score of the experimental group was higher than that of the control group, and the esthetic effect of the former was better than that of the latter (
CONCLUSIONS
The modified retroauricular hairline incision and sternocleidomastoid flap with an inferior pedicle can be applied to resect benign parotid gland tumors safely. It shows a better cosmetic effect and does not cause obvious postoperative complications. Therefore, it should be promoted for tumor treatments.
Esthetics, Dental
;
Humans
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Parotid Gland/surgery*
;
Parotid Neoplasms/surgery*
;
Postoperative Complications
;
Retrospective Studies
;
Sweating, Gustatory
5.Bisphosphonate-related osteonecrosis of the jaw caused by implant: a case report.
Ping-Fan WU ; Yu LI ; Zhen-Ge LEI ; Lin-Lin CHEN
West China Journal of Stomatology 2020;38(4):460-463
Osteonecrosis of the jaw could occur after intake of bisphosphonate drugs, which are widely used to treat osteoporosis and bone metastasis of malignant tumors. This effect has aroused concern among dentists. In this paper, a case of bisphosphonate-related osteonecrosis caused by implant is reported, and the pathogenesis, diagnosis, prevention, and treatment of bisphosphonate drug-induced osteonecrosis are described through a literature review. The effects of bisphosphonate drug treatment on dental implants are also discussed.
Bisphosphonate-Associated Osteonecrosis of the Jaw
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Bone Density Conservation Agents
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Dental Implants
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Diphosphonates
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Humans
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Osteoporosis
6.Effects of repeated immobilization stress on hypothalamic-pituitary- ovarian axis in female rats.
Jie HAN ; Zi Yi LIU ; Zhen FANG ; Lei TIAN ; Dan Feng YANG ; Zhu Ge XI ; Xiao Hua LIU
Chinese Journal of Applied Physiology 2020;36(3):245-249
To explore the effects of repeated immobilization stress on hypothalamic-pituitary-ovarian axis in female rats. Methods: Forty female SD rats were randomly divided into two groups: control group (n=20) and experimental group (n=20). One group was fed normally, the other group was subjected to incremental load restraint stress. Brake stress once a day in the retainer (starting at 9: 00 a.m.), braking for 2 hours on the first day, increasing load by 0.5 hours a day for two weeks. Body weight, estrous cycle, sex hormone, organ coefficient, pathology and expression of related genes were detected to explore the harm of hypothalamic-pituitary-ovarian axis. Repeated immobilization stress caused weight loss, prolonged estrous cycle, and changed the organ coefficient and morphology of ovaries and uterus. QPCR technique was used to detect the related genes. It was found that the expressions of gonadotropin releasing hormone, pituitary gonadotropin releasing hormone receptor, follicle stimulating hormone and luteinizing hormone mRNA were decreased significantly, while the expressions of ovarian follicle stimulating hormone and luteinizing hormone receptor mRNA were increased significantly. The expression of estrogen receptor mRNA in ovary and uterus was decreased significantly. Repeated immobilization stress may disrupt the estrous cycle by interfering with the endocrine regulation of the hypothalamic-pituitary-ovarian axis, thus damaging the gonadal and reproductive endocrine function of female animals.
7.Inflammatory mechanism of hippocampal tissue injury induced by PM in nasal drip in mice.
Zhen FANG ; Xi Hou HU ; Kang LI ; Jie HAN ; Lei TIAN ; Jun YAN ; Wei ZHANG ; Wen Qing LAI ; Ben Cheng LIN ; Xiao Hua LIU ; Zhu Ge XI
Chinese Journal of Applied Physiology 2020;36(3):240-244
To investigate the inflammatory mechanism of nasal instillation of fine particulate matter (PM)on hippocampal tissue injury in mice. Thirty C57BL/6J mice were randomly divided into 3 groups(n=10):control group, low-dose group, high-dose group. The nasal instillation doses of PM in the low-dose group and the high-dose group were 1.5 mg/kg BW and 7.5 mg/kg BW, respectively, and the control group was given saline with an equal volume. Saline was sprayed once every other time for 12 times. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were determined by ELISA method. HE staining and electron microscopy were used to observe the pathological changes and ultrastructure of lung tissue and hippocampus. The inflammatory cytokine levels in hippocampus were detected by antibody chip technique. There was no significant effect of PM nasal instillation on serum TNF-α, IL-1β and IL-6 levels (P>0.05), and there was no obvious pathological changes in lung tissue structure. In hippocampus, low-dose and high-dose PM exposure could lead to disordered neuronal arrangement in the hippocampal CA3 region, and there were neurological changes around the neuron cells and ultrastructural changes such as edema around small blood vessels. Compared with the control group, the levels of inflammatory cytokines such as CX3CL1, CSF2 and TECK in the low-dose group were increased significantly (P <0.05), while sTNFR1 was decreased significantly (P<0.05); the inflammatory factors CX3CL1, CSF2, and TCA-3 were significantly increased in the high-dose group (P<0.05), while leptin, MIG, and FASLG were significantly decreased (P<0.05). Nasal instillation of PM can induce tissue damage in the hippocampus of mice, and its mechanism of action may be the olfactory brain pathway. The increasing of TNF-α and IL-6 and the decreasing of sTNFR1 and FASLG may be involved in inflammatory mechanisms.
8.Nursing Grading Evaluation System for Patients with Stroke at Home: Construction, Validity and Reliability
Zhen-xiang ZHANG ; Chun-ge DING ; Chun-hui ZHANG ; Yong-xia MEI ; Bei-lei LIN ; Shao-yang WANG ; Sen YE
Chinese Journal of Rehabilitation Theory and Practice 2020;26(3):368-372
Objective:To construct a nursing grading evaluation indicator system for patients with stroke at home to provide a basis for graded care. Methods:Based on literature analysis, qualitative interviews and panel meeting, an evaluation indicator system was preliminarily drafted. June to September, 2018, the indicator system was consulted to experts three times. It was used to evaluate 210 patients with stroke at home from September to December, 2018 to test its reliability and validity. Results:The effective recovery rates of the three times of consultation were 85.00%, 89.47% and 100%, and the authority coefficient were 0.878, 0.879 and 0.879. The indicator system included four first-level indicators, 30 second-level indicators and 120 items. The scale-level content validity index (CVI) universal agreement was 0.733, average CVI was 0.927; the item-level CVIs were 0.83 to 1.00. For the overall level, the Cronbach's α coefficient was 0.928, and the Guttman Spilt half-factor coefficient was 0.794. For the dimensions, the Cronbach's α coefficient and the Guttman Spilt half-factor coefficients were all above 0.700. The correlated coefficients inter-evaluator of each indicators were 0.492 to 0.963 (
9.Effects of acute ozone exposure on genotoxicity of lung cells in rats.
Ning LI ; Hu YANG ; Zhen FANG ; Ping Yu WANG ; Jie HAN ; Lei TIAN ; Jun YAN ; Zhu Ge XI ; Xiao Hua LIU
Chinese Journal of Applied Physiology 2019;35(2):97-100
OBJECTIVE:
To clarify the genotoxicity induced by acute exposure of ozone with different concentrations on pulmonary cells in rats.
METHODS:
Thirty-six Wistar rats were randomly divided into control group (filtered air exposure) and ozone exposure group (0.12 ppm, 0.5 ppm, 1.0 ppm, 2.0 ppm, 4.0 ppm) with 6 in each group. After rats were exposed to different concentrations of ozone for 4 h, lung tissues were taken and single cells were isolated. Then, 8-hydroxydeoxyguanosine (8-OHdG) was quantitatively detected by enzyme-linked immunosorbent assay. Comet assay, micronucleus test and DNA- protein cross-linking assay were used to analyze DNA and chromosome damages.
RESULTS:
Compared with the control group, the content of 8-OHdG in lung tissue was increased significantly from the ozone exposure concentration of 0.12 ppm, reaching the highest value at 0.5 ppm. With the increase of ozone exposure concentration, the tail rate of comets was increased gradually, and there was a significant dose-effect relationship. The cross-linking rate of DNA- protein was increased first and then was decreased with a maximum value at 2.0 ppm group. Although the micronucleus rate of lung cells showed an upward trend, there was no significant difference compared with the control group.
CONCLUSION
Acute exposure of ozone at low concentrations (0.12 ppm) could lead to DNA damage in the pulmonary cells of rats, while no significant chromosome damage was found even in the group with ozone concentration reached to 4 ppm.
Animals
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Comet Assay
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DNA Damage
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Lung
;
cytology
;
pathology
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Micronucleus Tests
;
Ozone
;
adverse effects
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Random Allocation
;
Rats
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Rats, Wistar
10.Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury.
Dandan LUO ; Weihong GE ; Xiao HU ; Chen LI ; Chia-Ming LEE ; Liqiang ZHOU ; Zhourui WU ; Juehua YU ; Sheng LIN ; Jing YU ; Wei XU ; Lei CHEN ; Chong ZHANG ; Kun JIANG ; Xingfei ZHU ; Haotian LI ; Xinpei GAO ; Yanan GENG ; Bo JING ; Zhen WANG ; Changhong ZHENG ; Rongrong ZHU ; Qiao YAN ; Quan LIN ; Keqiang YE ; Yi E SUN ; Liming CHENG
Protein & Cell 2019;10(8):566-582
The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

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