Phenylalanine ammonia-lyase (PAL), which catalyzes the conversion from L-phenylalanine to trans-cinnamic acid, is a well-known key enzyme and a connecting step between primary and secondary metabolisms in the phenylpropanoid biosynthetic pathway of plants and microbes. Schisandra chinensis, a woody vine plant belonging to the family of Magnoliaceae, is a rich source of dibenzocyclooctadiene lignans exhibiting potent activity. However, the functional role of PAL in the biosynthesis of lignan is relatively limited, compared with those in lignin and flavonoids biosynthesis. Therefore, it is essential to clone and characterize the PAL genes from this valuable medicinal plant. In this study, molecular cloning and characterization of three PAL genes (ScPAL1-3) from S. chinensis was carried out. ScPALs were cloned using RACE PCR. The sequence analysis of the three ScPALs was carried out to give basic characteristics followed by docking analysis. In order to determine their catalytic activity, recombinant protein was obtained by heterologous expression in pCold-TF vector in Escherichia coli (BL21-DE3), followed by Ni-affinity purification. The catalytic product of the purified recombinant proteins was verified using RP-HPLC through comparing with standard compounds. The optimal temperature, pH value and effects of different metal ions were determined. V_max, K_cat and K_m values were determined under the optimal conditions. The expression of three ScPALs in different tissues was also determined. Our work provided essential information for the function of ScPALs.
Cloning, Molecular ; Escherichia coli/metabolism* ; Phenylalanine/metabolism* ; Phenylalanine Ammonia-Lyase/chemistry* ; Recombinant Proteins ; Schisandra/genetics*

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

Professor
Acupuncture ; Acupuncture Therapy ; Angina, Stable ; Combined Modality Therapy ; Humans ; Moxibustion

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

BACKGROUND: To prevent risk of life-threatening stent thrombosis, all patients need to undergo dual antiplatelet therapy (DAPT) for at least 6 weeks to 12 months after stent implantation. If DAPT is continued during noncardiac surgery, there is a risk of severe bleeding at the surgical site. Our study was to assess the risk of bleeding in patients with continued DAPT during orthopedic surgery. METHODS: The clinical data of 78 patients with coronary heart disease who underwent orthopedic surgery from February 2006 to July 2018 were retrospectively analyzed. Prior to orthopedic surgery, DAPT was continued in 16 patients (group I), 24 patients were treated with single antiplatelet therapy (group II), and 26 patients received low-molecular-weight heparin therapy for more than 5 days after the discontinuation of all antiplatelet therapies (group III). Twelve patients were excluded, as they had undergone minimally invasive surgery such as transforaminal endoscopy and vertebroplasty. The perioperative blood loss of each patient was calculated using Nadler's formula and Gross' formula. The intraoperative bleeding volume, total volume of intraoperative bleeding in addition to postoperative drainage, and total blood loss were compared between groups. The level of significance was set at P < 0.05. RESULTS: There were no significant differences between the three groups in age, intraoperative bleeding volume, total volume of intraoperative bleeding in addition to postoperative drainage, and total perioperative blood loss calculated by Nadler's formula and Gross' formula (all P > 0.05). Six patients experienced postoperative cardiovascular complications due to the delayed restart of antiplatelet therapy; one of these patients in group III died from myocardial infarction. CONCLUSIONS Continued DAPT or single antiplatelet treatment during orthopedic surgery does not increase the total intraoperative and perioperative bleeding compared with switching from antiplatelet therapy to low-molecular-weight heparin. However, the discontinuation of antiplatelet therapy increases the risk of serious cardiac complications.
Aged ; Aged, 80 and over ; Female ; Hemorrhage ; epidemiology ; etiology ; Humans ; Male ; Middle Aged ; Orthopedic Procedures ; adverse effects ; Orthopedics ; methods ; Platelet Aggregation Inhibitors ; therapeutic use ; Postoperative Complications ; Retrospective Studies

OBJECTIVETo investigate the relationship between NK cell count/activity and acute graft-versus-host disease (aGVHD) in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSA total of 26 patients who had undergone allo-HSCT from January to July 2015 were enrolled in this study. The NK cell count/activity in the peripheral blood of recipients on day 30 after allo-HSCT were monitored by using 4-color flow cytometry. The incidence of aGVHD in patients was evaluated by clinical manifestation combinating with related pathologic indicators, and the relationship between NK cell count/activity and aGVHD were analyzed.

RESULTSIn the aGVHD group and the no-aGVHD group, the NK cell count and activity on days 30 after allo-HSCT were 655±216 cells/µl vs 1169±372 cells/µl(P=0.002) and 7.3±3.6% vs 9.0±3.6% (P=0.008). In the II-IV grade aGVHD group and the 0-I grade aGVHD group, the NK cell count/activity were 617±220 cells/µl vs 1081±399 cells/µl (P=0.001) and 4.2±1.7% vs 8.3±3.5%(P=0.001). As compared with the 0-I grade aGVHD group, patients in the II-IV grade aGVHD group had higher relapse rate (57% vs 5%)(P=0.010) , lower 1-year progression-free survival(PFS) rate (43% vs 84%)(P=0.010).

CONCLUSIONNK cell count/activity on day 30 after allo-HSCT were closely relates with aGVHD, which may be a potential marker for aGVHD and can provide a new target for aGVHD therapy.

BACKGROUNDWhen compared with conventional abdominoperineal resection (APR), extralevator abdominoperineal excision (ELAPE) has been demonstrated to reduce the risk of local recurrence for the treatment of locally advanced low rectal cancer. Combined with the laparoscopic technique, laparoscopic ELAPE (LELAPE) has the potential to reduce invasion and hasten postoperative recovery. In this study, we aim to investigate the advantages of LELAPE in comparison with conventional APR.

METHODSFrom October 2010 to February 2013, 23 patients with low rectal cancer (T 3-4 N 0-2 M 0 ) underwent LELAPE; while during the same period, 25 patients were treated with conventional APR. The patient characteristics, intraoperative data, postoperative complications, and follow-up results were retrospectively compared and analyzed.

RESULTSThe basic patient characteristics were similar; but the total operative time for the LELAPE was longer than that of the conventional APR group (P = 0.014). However, the operative time for the perineal portion was comparable between the two groups (P = 0.328). The LELAPE group had less intraoperative blood loss (P = 0.022), a lower bowel perforation rate (P = 0.023), and a positive circumferential margin (P = 0.028). Moreover, the patients, who received the LELAPE, had a lower postoperative Visual Analog Scale, quicker recovery of bowel function (P = 0.001), and a shorter hospital stay (P = 0.047). However, patients in the LELAPE group suffered more chronic perineal pain (P = 0.002), which may be related to the coccygectomy (P = 0.033). Although the metastasis rate and mortality rate were similar between the two groups, the local recurrence rate of the LELAPE group was statistically improved (P = 0.047).

CONCLUSIONSWhen compared with conventional APR, LELAPE has the potential to reduce the risk of local recurrence, and decreases operative invasion for the treatment of locally advanced low rectal cancer.

Adult ; Aged ; Aged, 80 and over ; Digestive System Surgical Procedures ; methods ; Female ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; surgery ; Postoperative Complications ; Rectal Neoplasms ; surgery ; Rectum ; pathology ; surgery ; Retrospective Studies ; Treatment Outcome

BACKGROUNDPrimary liver cancer (PLC) is a common malignant tumor. Over the past decade, although farnesyltransferase (FTase) has emerged as a significant target for anticancer therapies and has become a hotspot of cancer research, its exact mechanism of action remains unknown. The aim of this study was to investigate the expression of FTase in PLC and its role in the development of PLC.

METHODSExpression of FTase was detected by real-time fluorescent quantitative-polymerase chain reaction (FQ-PCR) in cancer and surrounding normal tissues from 32 patients with PLC.

RESULTSExpression of FTase mRNA in PLC was significantly higher than that in normal hepatic tissues (P < 0.001). Overexpression of FTase was as high as 87.5%. The positive rate for FTase mRNA in the high tendency to metastatic recurrence group was obviously higher than that in the low tendency to metastatic recurrence group (P = 0.02). The positive rate for FTase mRNA in patients with metastatic recurrence during postoperative follow-up was also significantly higher than that in those without metastatic recurrence (P = 0.01).

CONCLUSIONSThe level of FTase mRNA expression in cancer tissues is much higher than in normal tissues. FTase may play an important role in the genesis and development of PLC and may be one of the reliable markers for the metastatic activity gained by liver tumor cells. FTase could be used clinically in predicting metastatic recurrence of PLC.

Adult ; Aged ; Farnesyltranstransferase ; genetics ; Female ; Humans ; In Vitro Techniques ; Liver Neoplasms ; enzymology ; pathology ; Male ; Middle Aged ; Polymerase Chain Reaction ; RNA, Messenger ; Young Adult

BACKGROUNDBariatric surgery offers successful resolution of type 2 diabetes mellitus (T2DM). However, recurrence of T2DM has been observed in a number of patients with initial resolution after bariatric surgery. This study aimed to induce reversal of the improvement of diabetes in T2DM rats after duodenal-jejunal bypass (DJB), and identify the effects of weight changes and gut hormones that might be involved.

METHODSDJB surgery was performed in two T2DM rat models (n=20 for each group): non-obese Goto-Kakizaki (GK) rats, and moderately-obese T2DM rats induced by a combination of a high-fat diet (HFD) and low-dose streptozotocin (HS rats). The controls were sham-operated and non-treated rats. All rats were then randomly divided into HFD- and low-fat diet (LFD)-fed groups. Glucose tolerance, insulin tolerance, glucose-stimulated insulin, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion, food intake and body weight were measured and compared with controls.

RESULTSDJB surgery resulted in a significant improvement in glucose tolerance in both GK and HS rats fed with either HFD or LFD. In contrast to LFD-fed rats, improved glucose tolerance was impaired in GK and HS rats fed with an HFD, accompanied by re-impairment of insulin tolerance and failure in enhancement of insulin secretion. There was no significant difference in food intake and body weight between DJB-operated and control rats, and between HFD- and LFD-fed rats. Glucose-stimulated GLP-1 and PYY levels were significantly increased after DJB surgery; however, they were not significantly different between HFD- and LFD-fed rats.

CONCLUSIONAn HFD reverses the improvement in glucose tolerance induced by DJB surgery in T2DM rats, primarily ascribing to the re-impairment of insulin sensitivity, but does not change body weight, GLP-1 and PYY levels.

Animals ; Blood Glucose ; drug effects ; Diabetes Mellitus, Type 2 ; blood ; chemically induced ; pathology ; surgery ; Diet, High-Fat ; adverse effects ; Gastric Bypass ; Glucose Tolerance Test ; Male ; Rats ; Rats, Sprague-Dawley