Objective To determine the acetylation level of nucleophosmin(NPM)in female breast cancer and to discuss its function through mutation of modified lysine sites.To construct positive and negative NPM mutants on its acetylated lysine sites and to express them in breast cancer cells.Methods Acetylation level and acetylated lysine sites of NPM in three breast cancer tissues and para-carcinoma tissues were detected by acetylome technology;NPM mutants were constructed by site-directed mutagenesis PCR,specific PCR products were digested by DpnI and transformed into Escherichia coli(E.coli)to obtain specific plasmids for mutants;The accuracy of mutants were verified by double restriction enzyme digestion and sequencing;The mutants were expressed in BT-549 cells by transient transfection and verified by RT-PCR method.Protein expression and acetylation level of NPM were validated by Western blotting;Function of NPM acetylation was analyzed by proteomic detection and bioinformatic analysis.Results The 27th and 32nd lysine of NPM were highly acetylated in breast cancer tissues,which were 2.76 and 2.22 times higher than those in adjacent normal tissues,respectively;The NPM mutants showed the same molecular weight as that of wild type NPM and contained expected mutation sites;Corresponding NPM mRNA levels of BT-549 cells transfected with NPM mutants were significantly increased.With the increase of wild type NPM expression level,NPM acetylation level increased,while decreased after 27th lysine underwent negative mutation.NPM acetylation can significantly change the expression levels of 101 proteins in BT-549 cells,which are enriched in regulation of cellular macromolecule biosynthesis,DNA-template transcription,RNA biosynthesis and RNA metabolism process.Conclusion NPM is highly acetylated in breast cancer and can play a key role in cellular macromolecule biosynthesis,DNA-templated transcription,RNA biosynthesis and RNA metabolism process.

Clostridioides difficile/genetics* ; Clostridioides ; Real-Time Polymerase Chain Reaction ; Feces ; Bacterial Proteins/genetics*

Toxicity-attenuating compatibility is an effective measure to ensure the safety of Chinese medicine. Involving the origin, processing method, compatibility mode, and dosage, it faces multiple challenges, such as the uncertainty of toxic substances, toxicity latency, indefinite safe dose, complex toxicity-efficacy relationship, and individual difference. As a result, research on clinical safety of Chinese medicine is limited by the consistency at "molecular-cellular-organ-overall" levels, unclear interaction of multiple medicinals and multiple substances, the "toxicity-efficacy-compatibility-syndrome" correlation, and the "dosage-time-toxicity-efficacy" conversion law. Therefore, following the principle of "starting from the clinical practice, verifying via the theoretical basis, and finally applying in clinical practice", we verified the toxicity at "molecular-cellular-organ-overall" levels, revealed the interaction of multiple medicinals and substances, collected evidence at multiple levels, clarified the "dosage-time-toxicity-efficacy" relationship, and tested the consistency between basic and clinical biomarkers. On this basis, we studied the toxicity-alleviating and efficacy-enhancing(preserving) compatibility characteristics, the fate of one medicinal and multiple medicinals in vivo, the molecular mechanism of toxicity, the "dosage-time-toxicity-efficacy" conversion law, and the clinical characteristics of toxic traditional Chinese medicine based on disease and syndrome. The three mechanisms of toxicity-attenuating compatibility reflect the seven-reaction theory in Chinese medicine compatibility. Finally, the strategies for safe use of Chinese medicine were proposed.
Drugs, Chinese Herbal/toxicity* ; Medicine, Chinese Traditional ; Research Design

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Migraine is a neurological disorder characterized by attacks of moderate or severe headache and various neurological symptoms. Acupuncture, as a commonly used non-pharmacological therapy, has the advantage of obvious therapeutic effect and few side effects in the prevention and treatment of migraine. But the underlying mechanism of acupuncture on migraine remains unclear. Recently, advances in neuroimaging technology have helped to objectively assess the effect of acupuncture on treating migraine and offered new opportunities to explore the central mechanism of acupuncture on treating migraine. In order to better understand the current status of neuroimaging studies on the therapeutic mechanism of acupuncture on migraine and shed light on future research, this review aims to overview the neuroimaging studies in recent 10 years from two aspects: (1) Central mechanism of acupuncture on treating acute migraine attack; (2) Central mechanism of acupuncture on preventing migraine attack.
Acupuncture Therapy ; Humans ; Migraine Disorders/therapy* ; Neuroimaging

OBJECTIVE: To explore clinical effect of acupoint application of Chinese herbal medicine in preventing postoperative nausea and vomiting after orthopaedic surgery under general anesthesia. METHODS: From January 2018 to December 2019, 168 patients who met inclusion criteria and were underwent selective spine surgery, were double-blind divided into two groups according to central random system, 84 patients in each group. In control group, there were 39 males and 45 females aged from 30 to 65 years old with an average of (53.83±9.17) years old, 37 patients were classified to typeⅠand 47 patients were typeⅡ according to American Society of Anesthesiologists (ASA) grading. In experiment group, there were 39 males and 45 females aged from 30 to 65 years old with an average of (54.08±9.00) years old; 32 patients were classified to typeⅠand 52 patients were typeⅡ according to ASA grading. Both of two groups were obtained acupoint application before anesthesia induction, and acupoint application were put on RESULTS: There were no statistical differences in incidence of nausea vomiting, VAS of narusea degree at 24 h after operation ( CONCLUSION The curative effect of acupoint application of traditional Chinese medicine on the prevention and treatment of postoperative nausea and vomiting is not obvious.
Acupuncture Points ; Adult ; Aged ; Anesthesia, General ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Humans ; Male ; Middle Aged ; Orthopedic Procedures ; Postoperative Nausea and Vomiting/prevention & control* ; Quality of Life

Intestinal Peyer's patches （PPs） are local immune tissues of the intestine， which are considered to be the main induction site of the intestinal mucosal immune response， and closely related to immune-related refractory enteropathies， such as ulcerative colitis and Crohn's disease. In recent years， more and more scholars have tried to find a new breakthrough for treating refractory enteropathies with a limited efficacy of clinical interventions through in-depth study of the relationship between PPs and enteropathy. Traditional Chinese medicine （TCM） polysaccharides are considered to be a key component for immune regulation with TCM. Modern studies show that TCM polysaccharides have a significant positive intervention effect on the structure and function of PPs， with good development prospects. Based on this， this paper focuses on PPs and intestinal-related diseases， and systematically introduces the physiological structure of PPs and their drug delivery mechanism， and summarizes the interactions of PPs with effect on immune-related enteropathies， analyze of current studies and prospects of effect of TCM polysaccharides in intervening intestinal disease and its dysfunction by regulating PPs， with the aim to provide new strategies for basic studies and clinical treatment of immune-related refractory enteropathies from the perspective of PPs， and new ideas for basic studies and clinical studies on effect of TCM polysaccharides in intervening enteropathies.

Objective To explore the protein acetylation/succinylation and histone 2AX (H2AX) expression levels in breast cancer, as well as their correlation. Methods By Western blotting and RT-PCR methods to detect the protein modification and H2AX expression levels in 11 breast cancer tissues and cells, as well as to explore the common regulation way of protein acetylation and succinylation by treatment of histone deacetylase inhibitors ; To study the relationship between H2AX expression level and protein modification level through the construction and over-expression of indicated plasmids. Results Compared with the adjacent normal tissues, there existed an increase protein acetylation/succinylation levels in breast cancer tissues, and the protein acetylation and succinylation were both regulated by histone deacetylase (HDAC) members. The H2AX mRNA and protein expression levels were increased both in breast cancer cell and tissues, its expression level and the expression and modification level of represented protein nucleophosmin 1(NPM1) showed a positive correlation. Conclusion The breast cancer possesses a characteristic of high protein acetylation/succinylation levels and high H2AX expression level, the H2AX expression level and the modification level of partial proteins in breast cancer have a positive correlation.

OBJECTIVE: To compare the therapeutic effect of plum-blossom needle tapping at three meridians of wrist combined with rehabilitation training and simple rehabilitation training on wrist joint contracture after stroke. METHODS: A total of 72 patients with wrist joint contracture after stroke were randomized into an observation group and a control group, 36 cases in each one. In the control group, simple rehabilitation training was applied, 5 times a week, 3 weeks as one course and totally 3 courses were required. On the basis of the treatment in the control group, plum-blossom needle tapping at three meridians of wrist was adopted in the observation group. The tapping regions were wrist traveling parts of three meridians of hand, ranging from up 3 to below 1 of wrist crease, 3 times a week, 3 weeks as one course and totally 3 courses were required. The active range of motion (AROM) of active wrist extension, Fugl-Meyer score (FMA) and Barthel index (BI) score were observed before and after treatment in the two groups. RESULTS: The AROM, FMA scores and BI scores after treatment in the two groups were superior to before treatment (<0.05), and the improvements of 3 indexes in the observation group were superior to the control group (<0.05). CONCLUSION The therapeutic effect of plum-blossom needle tapping at three meridians of wrist combined with rehabilitation training is superior to simple rehabilitation training on wrist joint contracture after stroke.
Acupuncture Therapy ; Contracture ; etiology ; therapy ; Humans ; Meridians ; Stroke ; complications ; Stroke Rehabilitation ; Treatment Outcome ; Wrist ; Wrist Joint

Objective N-acety-L-cysteine (NAC) can attenuate the injury of podocytes and renal tubular epithelial HK-2 cells induced by contrast agents, but its specific action mechanisms needs to be further clarified. In this study, we investigated the effects of NAC on iopromide (IPM)-induced injury and the NF-κB/NLRP3 signaling pathway in HK-2 cells. Methods Renal tubular epithelial HK-2 cells were divided into seven groups, control, IPM, and IPM + NAC at 2, 4, 8, 16 and 32 mmol/L. After a 24-hour treatment of the HK-2 cells with NAC, CCK-8, DAPI staining, DCFH-DA and Western blot were employed for determination of the viability, apoptosis and morphology of the cells as well as the level of reactive oxygen species (ROS) and the expressions of Bax, Bcl-2, NLRP3, ASC, Caspase-1, IL-1β and NF-κB in the cells. Results Compared with the control, the cells of the IPM group showed a significantly reduced viability ([100 ± 4.749]% vs [48.819 ± 2.045]%, P < 0.05), increased apoptosis, elevated ROS level, and up-regulated expressions of Bax, Bcl-2, NLRP3, ASC, Caspase-1, IL-1β and NF-κB. In comparison with the IPM group, the HK-2 cells treated with NAC at 2, 4, 8, 16 and 32 mmol/L exhibited a remarkably increased viability ([55.398 ± 3.609]%, [58.953 ± 2.859]%, [61.531 ± 5.179]%, [59.845 ± 6.365]% and [59.094 ± 6.285]%) and decreased ROS level and expressions of Bax, Bcl-2, NLRP3, ASC, Caspase-1, IL-1β and NF-κB. The mean fluorescence intensity was significantly higher in the HK-2 cells of the IPM group than in the control cells (5050.85 ± 606.76 vs 1502.17 ± 55.91, P < 0.05), but remarkably decreased in those treated with NAC at 2, 4, 8, 16 and 32 mmol/L (4065.39 ± 106.59, 4162.05 ± 28.93, 3675.71 ± 50.38, 3133.79 ± 66.07 and 2675.80 ± 92.39) (P < 0.05). Conclusion NAC can effectively improve IPM-induced injury of renal tubular epithelial cells, which may be associated with its abilities of inhibiting ROS production and activating the NF-κB/NLRP3 signaling pathway.