1.Design, synthesis and biological study of BTK/JAK3 dual-target inhibitors
Lifang CEN ; Ming CHENG ; Weijie REN ; Liu YE ; Luhua WANG ; Weibo GUO ; Qiang ZHANG ; Yungen XU
Journal of China Pharmaceutical University 2024;55(1):73-86
Abstract: In the present study, the compound XL-12 from our previous work was utilized as a lead compound. Through the optimization of the terminal phenyl ring, 12 target compounds were designed and synthesized. The structures of all target compounds were confirmed by 1H NMR, 13C NMR, and H RMS. In vitro enzyme activity assay showed that most compounds demonstrated significant inhibitory activity toward Bruton’s tyrosine kinase (BTK) and Janus kinase 3 (JAK3). Among them, compound I-3 exhibited moderate cell proliferation inhibitory activity toward Daudi cells and BaF3-JAK3 cells. In the evaluation of anti-inflammatory activity in vitro, compound I-3 could effectively inhibit the production of inflammatory factors IL-6; besides, it exhibited superior anti-inflammatory activity compared to ibrutinib in xylene-induced ear swelling model in mice.
2.Therapeutic effect of naringenin on diabetes retinopathy rats by regulating JAK2/STAT3/SOCS1 signaling pathway
Yanli SUN ; Lifang ZHANG ; Jian CHENG
Chinese Journal of Endocrine Surgery 2024;18(4):549-553
Objective:To investigate the therapeutic effect of naringenin on diabetes retinopathy (DR) rats by regulating Janus kinase 2 (JAK2) /signal transducer and activator of transcription 3 (STAT3) /suppressor of cytokine signaling 1 (SOCS1) signaling pathway.Methods:A DR rat model was constructed and randomly separated into DR group, naringenin group, activator group, and naringenin+activator group, with normal rats as the control group. After intervention according to corresponding groups, blood glucose and glycosylated hemoglobin of rats were detected. Retinal tissue was separated, and interleukin-6 (IL-6), IL-1β, glutathione (GSH), and catalase (CAT) were detected. The pathological changes in rats and blood retinal vascular barrier permeability were detected, and the retinal tissue adhesion factor 1 (VCAM-1), anti vascular endothelial growth factor (VEGF) mRNA, and JAK2/STAT3/SOCS1 pathway related proteins were detected.Results:In the control group, blood glucose levels were (5.16±0.53) mmoL, glycosylated hemoglobin (4.26±0.45) %, IL-6 (63.11±6.35) pg/mL, IL-1β (23.11±2.38) pg/mL, Evans blue (EB) content (4.72±0.49) ng/mg, VCAM-1 (1.02±0.11), VEGF mRNA expression (0.93±0.10), p-JAK2/JAK2 (0.24±0.03), p-STAT3/STAT3 (0.19±0.02), GSH (17.62±1.81) nmoL/mg, CAT (11.68±1.19) IU/mg, and SOCS1 expression 1.44±0.16; while in DR group, blood glucose were (18.85±1.89) mmoL, HBA1c (11.62±1.18) %, IL-6 (89.17±8.99) pg/mL, IL-1β (52.11±5.28) pg/mL, EB (10.24±1.08) ng/mg, VCAM-1 1.56±0.16, VEGF 1.61±0.18, P-JAK2/JAK2 0.55±0.06 and P-STAT3/STAT3 0.47±0.05, all decreased compared with that of the control group ( P<0.05). The expressions of GSH were (8.27±0.88) nmoL/mg, CAT (6.85±0.71) IU/mg and SOCS1 0.86±0.09 in group DR, all increased compared with those of the control group ( P<0.05). In naringin group, blood glucose was (13.11±1.34) mmoL, HBA1c (7.36±0.76) %, IL-6 (67.08±6.75) pg/mL, IL-1β (31.61±3.22) pg/mL, EB content was (6.15±0.63) ng/mg, VCAM-1 1.15±0.12, VEGF mRNA expression 1.17±0.12, P-JAK2 /JAK2 0.29±0.03, and P-STAT3 /STAT3 0.21±0.03, all lower than those in DR Group ( P<0.05). However, the expressions of GSH were (15.22±1.59) nmoL/mg, CAT (10.95±1.11) IU/mg, and SOCS1 (1.37±0.15) ,all higher than those of DR group ( P<0.05). The activator reversed the protective effect of naringenin on DR Rats. Conclusion:Naringenin improves DR rat injury by regulating the JAK2/STAT3/SOCS1 signaling pathway.
3.Characterization of chemical constituents of Heibu Yaogao (ointment)
Xiaohong CHENG ; Huijun LIU ; Li JIANG ; Lifang LIU
Journal of China Pharmaceutical University 2023;54(1):77-88
Heibu Yaogao (ointment), which made of Galla chinensis, Scolopendra, etc., is a commonly used hospital preparation with definite clinical efficacy, yet its material basis has not been fully clarified.By ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS), the chemical constituents of Heibu Yaogao (ointment) and its crude drug mixture were qualitatively analyzed, and the differences of components before and after preparation were discussed.Scanned by electrospray ionization (ESI) source in positive and negative ion modes, a total of 73 compounds were identified via precise molecular weight, characteristic fragment ions and chromatographic retention time.57 and 65 compounds were detected in crude drug mixture and Heibu Yaogao (ointment) respectively, including tannins, phenolic acids, nucleosides, amino acids, etc.In the process of preparation, the chemical structure changes are mainly concentrated in tannins.The change of components of Heibu Yaogao (ointment) before and after processing were proved by UPLC-Q-TOF-MS/MS, which provides important reference for elucidating the material basis of Heibu Yaogao (ointment), illustrating the rationality of preparation technology and further promoting the quality control of the preparation.
4.Influence of health literacy of rural junior middle school students on knowledge, attitudes and practices of COVID-19 protection in Jiangxi Province
ZHANG Cheng, DENG Lifang, WANG Naibo, XU Lewei, WU Lei, WAN Dezhi, LIU Yong
Chinese Journal of School Health 2023;44(3):375-378
Objective:
To understand the influence of junior middle school students health literacy on knowledge, belief and behavior of COVID-19 in rural areas of Jiangxi Province, and to enhance junior middle school students ability to deal with public health emergencies.
Methods:
Stratified cluster random sampling was used to investigate the health literacy, knowledge level and behavior of COVID-19 protection of 4 311 grade 7 to grade 8 students in rural areas of Jiangxi Province; Chi square test and Logistic regression analysis were used to analyze the correlation between junior high school students health literacy and COVID-19 protection knowledge, belief and behavior.
Results:
The rate of health literacy of junior middle school students in rural areas was 18.21 %( n =785), the reported rate of intermediate level was high ( n =2 454, 56.92%), and the reported rate of junior high school students at a low level of health literacy was 24.87%( n =1 072). The rate of junior middle school students in rural areas with good COVID-19 protection knowledge was 63.49%, the rate of positive protection attitude was 74.25%, and the rate of good protection behavior was 85.36%; Rate of COVID-19 protection knowledge ( OR=4.85, 95%CI =3.80-6.18) and positive rate of protection attitude of high level health literacy ( OR=44.07, 95%CI =24.57-79.05), protective behavior possession rate ( OR=25.99, 95%CI = 19.67-34.35) were higher than those with low level of health literacy( P <0.01).
Conclusion
Health literacy is associated with COVID-19 protection knowledge, belief and behavior in rural junior high school students of Jiangxi Province, the findings provide direction for junior middle school students to improve their ability to deal with public health emergencies.
5.Prenatal diagnosis and genetic analysis of a special case with complex structural rearrangements of chromosome 8.
Yan ZENG ; Tingting LUO ; Feiyan QIAN ; Dehua CHENG ; Caiping CHEN ; Jiaming FAN ; Lifang ZHANG ; Tao ZHANG ; Hongmei LI ; Zhiqiang WU
Chinese Journal of Medical Genetics 2023;40(9):1181-1184
OBJECTIVE:
To present on a prenatally diagnosed case with complex structural rearrangements of chromosome 8.
METHODS:
Chromosome karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) were carried out for a fetus with increased nuchal thickness.
RESULTS:
The karyotype of the amniotic fluid sample showed extra materials on 8p. FISH revealed a centromeric signal at the terminal of 8p with absence of telomeric signal. CMA revealed partial deletion of 8p23.3 [(208049_2256732)×1], partial duplication of 8p23.3p23.2 [(2259519_3016818)×3], and partial duplication of 8q [8q11.1q12.2(45951900_60989083)×3].
CONCLUSION
The complex structural rearrangements of chromosome 8 in this case has differed from the commonly seen inv dup del(8p).
Female
;
Pregnancy
;
Humans
;
Chromosomes, Human, Pair 8/genetics*
;
In Situ Hybridization, Fluorescence
;
Gene Rearrangement
;
Prenatal Diagnosis
;
Centromere
6.Accurate localization and successful treatment of 23 cases of migrating pharynx and cervical esophageal foreign bodies
Qiong XU ; Shuihong ZHOU ; Qinying WANG ; Yangyang BAO ; Zhe CHEN ; Lifang SHEN ; Libo DAI ; Yongcai LIU ; Kejia CHENG ; Quancheng LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(12):1206-1214
Objective:To explore clinical features, diagnosis, localization, and therapeutic strategy of migratory pharyngeal and cervical esophageal foreign bodies.Methods:A total 23 cases of pharyngeal and cervical esophageal migratory foreign bodies were admitted between January 2015 and December 2021. There were 14 females and 9 males with the age ranged from 35 to 82 (55.0±12.7)years. In all the cases, esophageal CT was taken to confirm the esophageal foreign body. Multiplanar reconstruction (MPR) was performed to locate the foreign body from the horizontal, coronal and sagittal dimensions as well as the corrected reconstructed MPR. According to the location of the foreign body, appropriate surgical method was selected.The symptoms, complications, types of foreign body, positioning, surgical methods, and relevant information were recorded.Data were analyzed using the descriptive method and SPSS 25.0 software.Results:The clinical symptoms of 23 migrating esophageal foreign bodies included pharyngodynia (20/23), foreign body sensation (6/23), hoarsenss (1/23), difficulty in turning neck(1/23), difficulty in opening mouth (1/23), fever (7/23), poor appetite (1/23), and abdominal pain (1/23). The foreign bodies included 19 fish bones, 2 wires, 1 embroidery needle and 1 chicken bone. There were 9 cases (39.1%) of foreign bodies located in extraluminal cervical esophagus, 2 cases (8.7%) of foreign bodies located in the muscular layer of the cervical esophagus and 12 cases (52.2%) of foreign bodies located in pharynx. Twenty-one cases of foreign bodies were removed by cervical lateral incision, in which 11 were removed by cervical lateral incision directly, 10 by the second lateral cervical incision after the foreign bodies were accurately located by MPR and/or corrected MPR, 1 foreign body was removed by incision of the pharyngeal mucosa under suspension laryngoscope, 1 foreign body was removed by tracheoscopy. Compared with patients with intraluminal foreign bodies ( n=308) treated in the same period, intake of fishbone [19 (19/23) vs. 133 (82.6% (43.2%, 133/308), OR=7.31] and first visit was more than 24 hours [20(87.0%, 20/23) vs. 77(25.0%, 77/308), OR=17.2] were the significant risk factors of migratory esophageal foreign bodies. Conclusions:MPR and the corrected MPR can accurately locate the migrating pharyngeal and cervical esophageal foreign bodies, by providing more intuitive imaging evidence for doctors, which provide imaging basis for formulation of surgical programs. Foreign bodies in pharyngeal and cervical esophagus need to be treated as soon as possible, otherwise they are easy to migrate, leading lead to serious complications.
7.Genetic analysis of a fetus with mosaicism of 13q inversion duplication.
Tingting LUO ; Ming CHE ; Dehua CHENG ; Lifang ZHANG ; Tao ZHANG ; Yan ZENG
Chinese Journal of Medical Genetics 2022;39(1):76-80
OBJECTIVE:
To report on a case of mosaicism 13q inversion duplication, analyze its mechanism, and discuss the correlation between its genotype and phenotype.
METHODS:
Amniotic fluid and umbilical cord blood were collected at 23 and 32 weeks of gestation, respectively. Combined with G-banding chromosome karyotyping analysis, single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) were used to confirm the result.
RESULTS:
The karyotype of the fetus was determined as 47,XY,+inv dup(13)(q14.3q34)/46,XY. After careful counseling, the couple decided to continue with the pregnancy, and had given birth to a boy at 40 weeks' gestation. Except for a red plaque (hemangioma) on the nose bridge, no obvious abnormality (intelligence to be evaluated) was discovered.
CONCLUSION
To provide reference for clinical genetic counseling and risk assessment, the location and proportion of new centromere formation should be fully considered in the case of mosaicism 13q inversion duplication.
Amniocentesis
;
Chromosome Inversion/genetics*
;
Comparative Genomic Hybridization
;
Female
;
Fetus
;
Humans
;
In Situ Hybridization, Fluorescence
;
Male
;
Mosaicism
;
Pregnancy
;
Prenatal Diagnosis
8.Identification of chemical constituents in Fufang Shechuangzi Xiji(Lotion)by UPLC-Q-TOF-MS/MS
Xiaohong CHENG ; Li JIANG ; Xingting DONG ; Xiulin KANG ; Lifang LIU
Journal of China Pharmaceutical University 2022;53(4):452-466
Fufang Shechuangzi Xiji (Lotion) is a common hospital preparation made from clinical prescriptions. Its clinical efficacy is accurate, yet its pharmacodynamic material basis has not been clarified.An ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) technique was developed to identify the chemical constituents of Fufang Shechuangzi Xiji (Lotion).The chemical constituents of Fufang Shechuangzi Xiji (Lotion) were scanned by electrospray ionization (ESI) source in positive and negative ion modes.As a result, a total of 118 compounds were identified and characterized via reference standards and by comparing mass spectrometry data with literature, including 45 alkaloids, 21 coumarins and chromones, 19 flavonoids, 14 saponins, 10 anthraquinones and 9 organic acids.As a result, UPLC-QTOF-MS/MS technology can quickly and sensitively identify the chemical constituents of Fufang Shechuangzi Xiji (Lotion), which provides a useful reference for exploring the pharmacodynamic material basis and further quality control study of the preparation.
9.Development of plasma quality control material for non-invasive prenatal detection of fetal aneuploidy
Yan ZENG ; Tao ZHANG ; Yandi QIAN ; Yuling GAO ; Cheng XIONG ; Yunqin NI ; Tingting LUO ; Lifang ZHANG ; Feiyan QIAN
Chinese Journal of Laboratory Medicine 2022;45(5):444-448
Objective:To develop a self-made plasma quality control material for non-invasive prenatal testing (NIPT) and evaluate its performance.Methods:139 NIPT-negative maternal plasmas stored in the genetic department of Shaoxing maternal and child health hospital from January 1, 2019 to June 30, 2021 were divided into male groups (19 cases) and female groups (120 cases) according to the neonatal gender. 9360 cases from September 2020 to September 2021 were enrolled as clinical validation cases.First step, 200 μl plasma from a 47 years-old non-pregnant healthy women was used as a matrix. Different amounts (0.1, 0.2, 0.5, 2.5, and 5 μl) of positive DNA from fetal chromosome aneuploidy (T21, T18, T13) detection kit were added. The appropriate volume of positive DNA was 0.5 μl according to the test results. Second step,Plasma in male and female group was treated as matrix. 0.5 μl positive DNA was added per 205 μl. Plasma matrix from female group showed good repeatability and the sensitivity was 100%.Third step, evaluate the self-made plasma quality control material, including storage stability, matrix uniformity and repeatability, and the effect of different batch numbers of positive DNA, by calculating Z score and the CV of fetal DNA concentration (FF).Results:Plasma matrix from female group showed good repeatability and the sensitivity was 100%, while the sensitivity of male group was only 84%. The CV of FF in female matrix was 3.9% in the repetitive experiments. After adding 0.5 μl positive DNA, the mean FF of self-made positive plasma quality control was 5.63%±0.42%, Z values>6, and the CV was 7% after storage of three months. Considering the concentration variation of positive DNA in different lots, 1 μl of positive DNA should be added when the FF of positive DNA is lower than 10%.Used in 9360 clinical cases from September 2020 to September 2021, all positive plasma quality control materials showed positive results, and the positive predictive value of trisomy 21 was 100%.Conclusions:The NIPT self-made positive plasma quality control material has been successfully developed in this study. The preliminary experimental results show that it has good repeatability and stability, which is suitable for clinical application.
10.Incidence of unintended pregnancy within 2 years after delivery and its influencing factors in China
Caixia YANG ; Xuhong ZHAO ; Yuyan LI ; Yanfei ZHOU ; Lin'ai ZHANG ; Dong YUAN ; Wei XIA ; Jianmei WANG ; Jiandong SONG ; Wen LYU ; Yongfeng LUO ; Lifang JIANG ; Li JIANG ; Xiaochen HUANG ; Xiaoyu HU ; Xiaojing DONG ; Tongyin CHENG ; Yuanzhong ZHOU ; Yan ZHANG ; Yan CHE
Chinese Journal of Obstetrics and Gynecology 2021;56(9):616-621
Objective:To investigate the present situation of unintended pregnancy within two years postpartum and its influencing factors in China.Methods:Participants who delivered a live birth at 60 hospitals in 15 provinces in the eastern, central and western regions of China during July 2015 to June 2016 were interviewed by using structured questionnaire. Information on occurrence of unintended pregnancy within 2 years after delivery, postpartum contraceptive use, sexual resumption, breastfeeding, and women′s socio-demographic characteristics, and so on, were collected. Life-table analysis, cluster log-rank tests and a 2-level Cox regression model were used for data analysis.Results:A total of 18 045 postpartum women were investigated. The cumulative 1- and 2-year unintended pregnancy rates after delivery were 5.3% (95% CI: 4.5%-6.1%) and 13.1% (95% CI: 11.3%-14.8%), respectively. Cox regression model analysis showed that the risk of unintended pregnancy within 2 years postpartum were increased in younger women, ethnic minorities, women with abortion history, and those who had a vaginal delivery with short lactation time and late postpartum contraceptive initiation (all P<0.01). The risk of postpartum unintended pregnancy was not associated with geographic regions and hospitals where women gave a birth (all P>0.05). Conclusions:In China, the risk of unintended pregnancy within 2 years after delivery is relatively high. Service institutions and service providers should improve the quality of postpartum family planning services, promote the use of high effect contraceptive methods, and educate women to use a method at the time of their sexual resumption or even before.


Result Analysis
Print
Save
E-mail