OBJECTIVE To explore and analyze the adverse drug event （ADE） signals of darolutamide and provide a reference for its clinical safe use. METHODS ADEs related to darotamide were collected based on the US FDA adverse event reporting system （FAERS） database from the third quarter of 2019 to the third quarter of 2022. Data mining and analysis were conducted by the report odds ratio （ROR） and proportional reporting ratio （PRR） methods. RESULTS A total of 565 ADE reports related to darolutamide were extracted， 356 ADE reports about darolutamide as the primary suspected drug were included， 38 ADE signals with darolutamide as the primary suspected drug were excavated， involving 15 system organ class （SOC）， mainly concentrated in patients over 65 years old. The SOC of darotamide ADE signal mainly focused on various examinations， systemic diseases and various reactions at the administration site， benign/malignant tumors or those with unknown nature （including cystic and polypoid）， kidney and urinary system diseases. A total of 13 ADE signals not mentioned in the instructions included increased prostate-specific antigen， dysphagia， cognitive impairment， erectile dysfunction， rhabdomyolysis， gynecomastia and decreased platelet count， etc. CONCLUSIONS When using darolutamide， in addition to ADE in the drug instruction， we should pay close attention to potential ADE， such as increased prostate-specific antigen， rhabdomyolysis， gynecomastia and decreased platelet count， so as to avoid drug withdrawal or organ damage caused by ADE.

Objective:To compare the clinical efficacy of 1 h and 12 h getting out of bed after transradial percutaneous coronary intervention (PCI), and to provide evidence for early safe getting out of bed after PCI.Methods:The quasi-experimental method was used in this study. A total of 84 patients undergoing radial artery PCI in the Cardiovascular Center of the Affiliated Hospital of Gansu University of Chinese Medicine from July 2022 to May 2023 were selected by purpose sampling method, and were divided into the control group and the experimental group by random number table method, with 42 patients in each group. The control group was given 12 h post-operative getting out of bed activity program, and the experimental group was given 1 h post-operative getting out of bed activity program. The quality of life and self-care ability of daily life were compared before and after intervention. Besides patients′ rehabilitation satisfaction was compared after intervention.Results:Ultimately there were 42 patients in each group completed the research. In the control group, there were 24 males, 18 females, aged (66.08 ± 6.78) years old; in the experimental group there were 22 males, 20 females, aged (68.03 ± 7.17) years old. Before intervention, there were no significant differences in quality of life, self-care ability of daily life and adverse cardiac events between 2 groups (all P>0.05). After intervention, the scores of quality of life in physical function, social relationship, emotional function and environment were (77.20 ± 4.17), (42.40 ± 3.71), (68.10 ± 4.74) and (76.90 ± 4.38), respectively. Higher than (74.50 ± 3.91), (40.20 ± 3.94), (67.70 ± 3.88), (74.35 ± 3.41) in the control group, the differences between the two groups were statistically significant ( t values were 2.17-2.98, all P<0.05). The scores of daily self-care ability in grooming, eating, dressing, going to the toilet, going up and down stairs, bed chair transfer and flat walking were (4.62 ± 1.33), (6.37 ± 2.26), (8.00 ± 2.48), (6.25 ± 2.46), (4.62 ± 2.08), (10.12 ± 3.09), (10.50 ± 3.54) points, higher than the control group (4.06 ± 1.96), (5.75 ± 1.79), (6.37 ± 2.26), (5.25 ± 1.10), (3.37 ± 2.62), (8.75 ± 2.19), (8.87 ± 2.11) points. The differences between the two groups were statistically significant ( t values were 2.29-3.30, all P<0.05). The scores of rehabilitation satisfaction of experimental group in rehabilitation treatment effect, team professional level and rehabilitation treatment arrangement were (4.55 ± 0.50), (4.82 ± 0.38), (4.77 ± 0.42) points, respectively, which were higher than (4.20 ± 0.64), (4.47 ± 0.64), (4.40 ± 0.81) points of control group. The differences between the two groups were statistically significant ( t=2.69, 2.96, 2.59, all P<0.05). Conclusions:Getting out of bed 1 h after radial artery PCI is safe and effective, which can significantly improve patients′ quality of life, self-care ability and satisfaction.It is expected to be clinically promoted and trialed.

Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate C_pk integrated Bootstrap-t. The C_pk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.

Autosomal recessive congenital ichthyosis (ARCI) is characterized by being born as collodion babies, hyperkeratosis, and skin scaling. We described a collodion baby at birth with mild ectropion, eclabium, and syndactyly. Whole exome sequencing showed a compound heterozygous variant c.[56C>A], p.(Ser19X) and c.[100G>A], p.(Ala34Thr) in the PNPLA1 gene [NM_001145717; exon 1]. The protein encoded by PNPLA1 acts as a unique transacylase that specifically transfers linoleic acid from triglyceride to ω-hydroxy fatty acid in ceramide, thus giving rise to ω-O-acylceramide, a particular class of sphingolipids that is essential for skin barrier function. The variant was located in the patatin core domain of PNPLA1 and resulted in a truncated protein which could disrupt the function of the protein. This case report highlights a novel compound heterozygous mutation in PNPLA1 identified in a Chinese child.
Humans ; Infant, Newborn ; Acyltransferases/genetics* ; Ceramides/metabolism* ; Collodion ; Ichthyosis, Lamellar/genetics* ; Lipase/metabolism* ; Mutation ; Phospholipases/genetics*

Objective:To explore the expression of peptidyl prolyl cis-trans isomerase (Pin1) activity in peripheral blood of patients with rheumatoid arthritis (RA) and the value and correlation of T helper cell 17/regulatory cells (Th17/Treg) cells, and to analyze the effect and influence of all-transretinoic acid (ATRA) on it.Methods:① Comparing the difference of Pin1 expression and absolute counts of Th17 and Treg between RA patients before and after treatment and healthy control group, Kruskal-Wallis rank sum test was used for analysis. ② To analyze the correlation between the expression of Pin1 and its general data, activity indicators [such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and disease activity score 28 joints (DAS28) scores], Th17, Treg and some cytokines in RA patients, and to use Pearson and Spearman correlation tests. ③ To analyze the difference of Pin1 expression and Th17/Treg in peripheral blood of RA patients treated with low-dose all-trans retinoic acid (10 mg twice a week) and traditional immunosuppressants such as hydroxychloroquine for 3 months respectively. Mann-Whitney U test was used for comparison between the two groups, and the difference was statistically significant with ( P<0.05). Results:① The activity of Pin1 in peripheral blood of the newly treated group of RA was [13.62(9.16, 19.42)] higher than that of the healthy control group [8.97(7.62, 11.45)]( Z=42.82 , P<0.05), and Th17 was [18.28(12.76, 24.08)] higher than that of the healthy control group [6.04(4.96, 4.96)]( Z=48.83 , P<0.05). Treg [11.06(5.31, 21.87). It was lower than that of healthy control group [40.41(24.33, 48.52)]( Z=42.21 , P<0.05). ② the activity of Pin1 in peripheral blood of RA patients was positively correlated with CRP, the number of involved joints, DAS28 score, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) ( r=0.396, P<0.05; r=0.683, P<0.05; r=0.466, P<0.05; r=0.315, P<0.05; r=0.416, P<0.05). ③ Compared with the newly treated RA group, the activity of Pin1 [6.94(5.96, 8.77), Z=42.82 , P<0.05] and Th17 7.38 decreased [7.38(3.85, 11.21), Z=48.83 , P<0.05], while Treg [40.41 (17.77, 33.47)] increased ( Z=42.21 , P<0.05). ④ Compared with the traditional medicine group, Treg [28.9(21.73, 37.36)] was higher in the retinoic acid group, and the difference was statistically significant ( Z=-2.683 , P<0.05). The activity of Pin1 was [6.23(5.58, 8.75)], but there was no statistical significance ( Z=-1.622 , P=0.104). Conclusion:Pin1 in peripheral blood of RA patients is over-expressed. Th17 is increased and Treg is decreased. ATRA combined with other traditional drugs can reduce Pin1 activity, promote Treg growth and improve disease activity of RApatients to a certain extent.

Objective:To explore the application value of dynamic monitoring of serum soluble interleukin-2 receptor (sIL-2R) and stromal cell-derived factor 1 α (SDF-1α) in patients with acute leukemia (AL).Methods:A total of 187 patients with AL admitted to the Second Hospital of Shanxi Medical University from March 2017 to August 2018 were selected and 90 healthy subjects at the same period were selected as the healthy controls. The levels of serum sIL-2R and SDF-1α were detected at the initial diagnosis, remission phase and relapse phase, respectively. The clinical value of dynamic monitoring of sIL-2R and SDF-1α was analyzed.Results:Among 187 patients with AL, 135 patients (72.19%) had complete remission (CR) after chemotherapy, 52 patients (27.81%) had partial remission, and 43 patients (31.85%) relapsed. The level of serum sIL-2R at the AL initial diagnosis period was (533±32) U/ml, which was higher than that in the healthy controls [(247±30) U/ml], and the difference was statistically significant ( t = 71.976, P < 0.01); the level of serum SDF-1α at the AL initial diagnosis was (2 968±305) pg/ml, which was higher than that in the healthy controls [(1 358±160) pg/ml], and the difference was statistically significant ( t = 47.043, P < 0.01). The levels of serum sIL-2R [(308±30) U/ml] and SDF-1α [(1 576±184) pg/ml] in the CR phase were lower than those in the initial diagnosis of patients with AL; and the levels of sIL-2R [(599±36) U/ml] and SDF-1α [(2 894±301) pg/ml] in the relapse phase were higher than those in the CR phase of patients with AL (all P < 0.01). Conclusions:The levels of serum sIL-2R and SDF-1α in patients with AL are increased, and there are big differences in the levels of sIL-2R and SDF-1α at the initial diagnosis, remission phase, and relapse phase. Dynamic monitoring of both can provide the data support for early clinical intervention.

OBJECTIVE：To establis h the evaluation model of hospital pharmacist post value of dispensing department ，and to provide scientific basis for optimizing the performance management of pharmacists in despensing department in hospital. METHODS：Based on factor counting method ，combined with questionnaire ，Delphi expert correspondence method and so on ，the hospital pharmacist post value evaluation model was established. Based on this ，the relative value scores of the pharmacists in the dispensing department was determined. RESULTS ：Hospital pharmacist post value evaluation model was established with 5 evaluation dimensions （knowledge，skills，responsibility，work autonomy ，work environment and intensity ，of which the first level weight coefficients were 0.194，0.166，0.365，0.216 and 0.058，respectively）and 31 evaluation elements. The above 5 evaluation dimensions contained 5，8，9，3，6 evaluation elements ，respectively，and the corresponding second-level weights were 0.052-0.431 （for example ，responsibility dimension with the highest weight ，including quality and safety control ，decision responsibility，responsibility for finance and assets ，the corresponding second-level weight coefficients were 0.279，0.140，0.132， respectively）. The relative value scores of 13 pharmacist post were 342.9-840.4 in the dispensing department of our hospital with this model ，among which the department responsible person had the highest score （840.4）and the prescription post score was the lowest（342.9）. CONCLUSIONS ：The hospital pharmacist post value evaluation model constructed by factor counting method can provide a scientific and reliable theoretical basis for realizing the rewards of different positions in the dispensing department.

Purpose: Cervical cancer is one of the most fatal diseases among women in under-developed countries. To improve cervical cancertreatment, discovery of new targets is needed. In this study, we investigated the expression of NUP210, miR-22, and Fas in cervicalcancer tissues and their functions in cell cycle regulation. Materials and Methods: We detected and compared the expression levels of NUP210, miR-22, and Fas in cervical cancer tissueswith paired normal tissues using immunohistochemistry, Western blot, and real-time quantitative polymerase chain reaction.NUP210 was knocked down in HeLa cells via lentivirus, followed by cell cycle and proliferation analysis. Using a luciferase reporterassay, we explored the link between miR-22 and NUP210. We overexpressed miR-22 in HeLa cells and analyzed cell cycle and proliferationfunction. We then overexpressed miR-22 in NUP210 knockdown cells to explore the connection between Fas and miR-22-NUP210 signaling. Results: We found that NUP210 was overexpressed in cervical cancer patients. Knocking down NUP210 restored cell apoptosisand proliferation. We confirmed miR-22 as a regulator of NUP210 and verified that miR-22 was inhibited in cervical cancer development.We also found that restoring miR-22 expression could induce cell apoptosis. Finally, we found that miR-22-regulated expressionof NUP210 could alter Fas expression and, in turn, elicit cell cycle arrest and proliferation. Conclusion miR-22 in cervical cancer is downregulated, resulting in NUP210 overexpression and inhibition of Fas-induced cellapoptosis.

With the sequence of the vasoactive intestinal peptiepeptide (VIP) from humans and according to the condon bias of Pichia pastoris, we designed PCR primers of VIP and obtained the sequence of VIP by SOE-PCR. Then VIP gene was cloned into Pichia pastoris secretory expression vector and the cell secretary system GS115-pPICZαA-vip was constructed. The recombinant strain was induced by methanol for 96 hours, and we collected the supernatant and identified the VIP by mass spectrometry. The molecular weight of VIP was consistent with theoretical molecular weight. The final result showed that the target peptide VIP was successfully expressed. The experimental investigations of agarose gel diffusion revealed that the recombinant expression modified VIP had relatively strong antibacterial activity to E. coli ATCC25922 and S. aureus ATCC25923. The minimal inhibitory concentration (MIC) of VIP to E. coli ATCC25922 and S. aureus ATCC25923 was 8 mmol/L and 16 mmol/L. Further cytotoxicity and hemolytic experiments indicated that recombinant VIP was non-toxic to normal cells NCM460 and IPEC-J2, had little hemolysis activity to SD rat erythrocytes. Meanwhile, by transmission electron microscopy, we found that VIP mainly inhibited bacteria by disrupting the cell membrane. These experiments established a useful system for further studies, application and mass production of antimicrobial peptide VIP.

Objective To observe the local field potential activity of dorsomedial and dorsolater striatal (STR) neurons in rats with exercise-induced fatigue,so as to explore the regional characteristics of those neurons.Methods Thirty-six male Wistar rats were randomly divided into a control group(CG),a single fatigue group(SFG)and a repeated fatigue group(RFG),each of 12.The exercise-induced fatigue model was established according to a load-increasing treadmill running protocol.The CG did not do any treadmill running,SFG finished one-time exhaustive exercise while the RFG repeated exhaustive exercise 6 times.The extracellular glass microelectrode technique was used to record the spontaneous firing of dorsomedial(n=6)and dorsolateral(n=6)STR neurons in vivo to observe the discharging frequency,characteristics and types.Results (1)Spontaneous firing frequencies of striatal neurons in SFG were significantly higher than those of CG(P＜0.01),while those of RFG were significantly lower than SFG.(2) After repeated fatigues,there were significant decreases in the irregular firing pattern and significant increase in the explosive firing of striatal neurons compared with CG(P＜0.05).(3)After the single fatigue and repeated fatigue,the discharging frequency of dorsomedial medium spiny-like neurons increased significantly(P＜0.05),and that after repeated fatigue significantly higher than that of the dorsolateral(P＜0.01).The discharge frequency of the dorsomedial and dorsolateral fast-spiking neurons decreased significantly after repeated fatigues.The discharge frequency of dorsolateral large aspiny-like neurons of RFG was significantly higher than SFG,while that of the latter was significantly lower than CG(P＜0.05).Conclusions (1)Striatal neurons mediate exercise-induced fatigue and present regional characteristics,which might be due to dorsomedial and dorsolateral striatal neurons receiving different types of projection neurons.(2) Striatal fast-spiking neurons may play an important role in mediating the exercise-induced fatigue.