OBJECTIVE: To study the effects of Fuzheng Yiliu Granule (FZYLG)-medicated serum on apoptosis of liver cancer cells H22 from mice and its mechanism. METHODS: Liver cancer cells H22 from mice were incubated in culture media containing sera from rabbits medicated with different doses of FZYLG. Flow cytometry was used to examine the cell cycle and analyze the apoptotic rate of the H22 cells. The morphological changes of the H22 cells were observed by transmission electron microscope and the apoptosis related proteins Bcl-2 and Bax were examined by streptavidin-biotin peroxidase complex (SABC) method. RESULTS: FZYLG-medicated serum could influence the cell cycle and stop the proliferation of H22 cells at the G(1)/G(0) phase with apoptotic peak being detected. In culture media with FZYLG-medicated sera, the expression of Bcl-2 decreased while that of Bax increased as compared with that in culture medium with non-medicated serum (P<0.05). CONCLUSION: FZYLG-medicated serum can induce apoptosis of the liver cancer cells H22 by influencing the cell cycle, down-regulating the expression of Bcl-2 and up-regulating the expression of Bax.

OBJECTIVE:To investigate the utilization of opioid analgesic drugs in a hospital,so as to provide reference for ra-tional drug use in clinic. METHODS:The utilization of opioid analgesic drugs in the hospital during 2014-2016 was analyzed and compared retrospectively in terms of consumption sum,DDDs,DDC,B/A,etc. RESULTS:Annual consumption sum of opioid an-algesic drugs in the hospital increased slightly in 2015,but decreased significantly in 2016. Fentany transdermal patches(8.4 mg), Oxycodone and acetaminophen tablets and Remifentanil hydrochloride for injection always took up the first 3 places in the list of DDDs. DDDs of Fentanyl citrate injection(0.1 mg)and Morphine sulfate sustained-release tablets increased year by year;while DDDs of Fentany transdermal patches(4.2 mg)and Fentany transdermal patches(8.4 mg)decreased year by year. DDC of all opi-oid analgesic drugs decreased in 2016,with the cancel of drug price addition at the end of 2016. B/A values of most drugs were close to 1.0;while B/A value of Oxycodone hydrochloride sustained-release tablets(40 mg)was much less than 1.0,and that of Fentany transdermal patches(8.4 mg)and Oxycodone and acetaminophen tablets were significantly more than 1.0 for consecutive 3 years. CONCLUSIONS: The variety and specifications of opioid analgesic drugs in the hospital is comprehensive during 2014-2016. The clinical utilization of opioid analgesic drugs is generally rational,but still needs to be supervised effectively and par-ticularly,so as to improve standard use of opioid andalgesic drugs.

The historical surveillance results showed, there were 10 schistosomiasis cases in Huangshan City from 1994 to 2006. The survey in 2007 showed, the positive rates of blood examination for schistosomiasis in migrant workers and immigrant workers were 0.49% and 0.47% , respectively, but no schistosome-infected patients were detected by using the stool examination. An area with snails of 3 000 m~2 was found in the residence of the immigrant workers, but no infected snails were found. It is indicated that the mobile population has some impact on the transmission of schistosomiasis in the transmission-interrupted area. The surveillance and health education for the mobile population should be strengthened, and the imported infectious source should be prevented.

Adult rats chronic unpredictable stress model of depression (CUS) was adopted to elucidate the antidepressant pharmacological activity and related neurogenesis protective effect of the total flavonoids extract (licorice flavonoids, LF) from the Glycyrrhiza uralensis Fisch. cultivated locally in Ningxia. The rats were exposed to 9 kinds of unpredictable sequence of stressors and were given flavonoids (300 mg x kg(-1), 100 mg x kg(-1) and 30 mg x kg(-1)) for 28 days. The antidepressant effect was elucidated by open field test, forced swimming test and tail suspension test. The level of serum corticosterone was detected by radioimmunoassay. 5'-Bromo-2'-deoxyuridine (BrdU) labeling experiments was employed to study the neurogenesis protective activities. The flavonoids can increase the sum of line crosses and number of rears, and decrease the number of fecal boli produced in the open field test of the CUS rats. Also the flavonoids can decrease the immobility time in forced swim test as well as in the tail suspension test. In addition, the flavonoids (300 mg x kg(-1)) can decrease the serum corticosterone level of the CUS rats, and increase the number of the new born BrdU positive progenitor cells at the subgranular zone (SGZ) of dentate gyrus (DG) region in hippocampus. The results demonstrated that the total flavonoids extract from the cultivated Glycyrrhiza uralensis Fisch. could produce the anti-depressive effect on chronic unpredictable stress of depression model rats and its mechanism may be associated with its neurogenesis protective effect.

OBJECTlVE To investigate the antidepressant effect and reIated mechanism of the totaI fIavonoids extract parts( Iicorice fIavonoids,LF)from Glycyrrhiza uralensisFisch. cuItivated IocaIIy in Ningxia. METHODS Forced swimming test( FST)and taiI suspension test( TST)were adopted to study the antidepressant pharmacoIogicaI effect in the acute stress-induced depression modeI in mice. The Km mice were intragastricaIIy administered with LF(5,30 and 180 mg·kg-1 )once daiIy,for 21 con-secutive days. One hour after the first,seventh and Iast administrations,the mice were submitted to FST by recording the immobiIity period within the Iast 4 min of the totaI 6 min in both tests and the resuIts were expressed as decrease in immobiIity period with respect to vehicIe controI. In TST,the other group of Km mice was used to evaIuate the antidepressant effect in same protocoI. In the antagonism of reserpine-induced symptoms test( ART),ICR mice were administered intragastricaIIy with LF( 50,150 and 400 mg·kg-1 )once daiIy for 7 consecutive days. One hour after the Iast administration,the mice received reserpine(4 mg·kg-1 ,ip),and ptosis or akinesia was measured 1 h after reserpine injection whiIe rectaI temperature was measured 4 h after the reserpine injection respectiveIy. The same protocoI was adopted in yohimbine toxicity potentiation test(YTT)as in ART. Thirty minutes fter the Iast adminis-tration,the mice received the threshoId IethaI dosage of yohimbine(30 mg·kg-1 ,sc)respectiveIy,and the death number of the mice was caIcuIated in 24 h after the yohimbine administration. In the 5-hydroxy-L-tryptophan(5-HTP)induced head-twitches test(HTT)in mice,after being administered intragastricaIIy with LF(50,150 and 400 mg·kg-1 )once daiIy for 7 consecutive days,the mice received pargiIine (100 mg·kg-1 ,ip)the next day,and 30 min Iater,5-HTP(10 mg·kg-1 ,ip)was intraperitoneaIIy injec-ted to induced the head twitch respectiveIy,and the times of head twitch in a 30 min period after 5-HTP treatment were observed at 6 time points. After HTT,the mice were sacrificed quickIy,and the mono-amine oxidase(mAO)activity in the brain cortex,hippocampus and thaIamus was examined to evaIuate the antidepressant effect of fIavonoids with mAO inhibition. RESULTS Compared with the vehicIe controI,LF significantIy decreased the immobiIity period in both FST and TST(P﹤0.05). LF(50,150 and 400 mg·kg-1 )antagonized the ptosis and akinesia symptoms respectiveIy in 1 h after reserpine administration( P ﹤ 0. 05 ), but faiIed to antagonize hypothermia produced 4 h after reserpine administration. AIso,at the same dosage,LF did not synergeticaIIy produce the enhancement of death by subcutaneous injection of yohimbine at the threshoId IethaI dosage. LF(150 and 400 mg·kg-1 )couId significantIy and synergeticaIIy increase 5-HTP induced head-twitches response(P﹤0.05),but LF couId not promote mAO activity in the cortex,hippocampus and thaIamus at the same dosage. CONCLUSlON LF exerts antidepressant-Iike effect on the modeI of acute despair test. The mechanism might be reIated to direct enhancement of the serotonergic neuraI function in the brain.

Genomic studies of cancer cell alterations,such as mutations,copy number variations(CNVs),and translocations,greatly promote our understanding of the genesis and development of cancers.However,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties.To explore the 3D genome structure in clin-ical lung cancer,we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer,combining with RNA sequenceing analysis.We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells(1×104),compared the genome architecture between clinical samples and cell lines of lung cancer,and identified conserved and changed spatial chromatin structures between normal and cancer sam-ples.We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer.By integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene expression.We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures.Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.

Objective: To investigate the mechanism of Al (mal) ₃-induced ferroptosis in rat adrenal pheochromocytoma cells (PC12), to explore the effect of deferoxamine (DFO) . Methods: Taken PC12 cells growing at logarithmic phase and divided into 6 groups: control group, 200 μmol/L Al (mal) ₃ group, 0.5% DMSO group, 200 μmol/L DFO group, Al (mal) ₃+DMSO group, Al (mal) ₃+DFO group. DMSO and DFO were added to the DMSO group and the Al (mal) ₃+DMSO group, the DFO group and the Al (mal) ₃+DFO group for 2 h, respectively, Al (mal) ₃ was then added to the Al (mal) ₃ group, Al (mal) ₃+DMSO group, and the Al (mal) ₃+DFO group to a final concentration of 200 μmol/L. The cell viability was detected by CCK8, the morphology and ROS levels of PC12 cells was observed by inverted microscope, the cell proliferation toxicity and intracellular iron ion content were detected by colorimetry, the GSH content and GSH-PX activity were detected by biochemical method. Results: Al (mal) ₃ exposure significantly inhibited the growth of PC12 cells and destroyed the cell morphological structure, resulting in increased LDH activity and intracellular iron ion content in PC12 cells, decreased GSH content and GSH-PX activity, increased ROS levels; the combined treatment of Al (mal) ₃+DFO can significantly improve the cell viability of PC12 cells, improved cell morphology, decreased cell LDH activity and intracellular iron ion content (P>0.05), increased GSH content and GSH-PX activity, decreased ROS levels. Conclusion Al (mal) ₃ can induce ferroptosis in PC12 cells, DFO may inhibit ferroptosis by reducing intracellular iron levels and reducing oxidative damage.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with metabolic stability tests and pharmacokinetic profiling, a representative compound () was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.
Chromatin ; Chromosomes ; Genome ; Humans ; Lamin Type B/genetics*