T, p.R394W in exon 9.

ObjectiveTo evaluate the efficacy and safety of domestic taerolimus in the manage-ment of acute rejection in renal transplantation reeipienta.MethodsA multieeneter, open and com-parative study for domestic Taerolimua and Prograf was performed. Eighty reeipienta of first allogenie renal transplantation were randomized into 2 groups: ①Experimental group (accepting Fumeixin ad-ministration, n=58) included 23 males and 35 females with the mean age of(39.1±9.6)years. ②Control group(accepting Prograf administration, n=22) included 12 males and 10 females with the mean age of(41.34±8.5)years. There was no significant difference in the volume, warm and cold is-chemia time of donor renal, age and sex of donor. All of the 80 cases accepted tacrolimus (domestic or foreign made, at the dose of 0. 10～0. 15 mg·kg-1·d-1 , q 12 h) treatment that combined with MMF and prednisone posttransplantation. Tacrolimus CO was aimed to 8-12 ng/ml in the first 60 days and 5-10 ng/ml later. The dose of MMF was according to the rule of each transplantation center based on the following recommendation: 1.5-2.0 g/d for the weight above 70 kg, 1.5 g/d for the weight 50-69 kg, and 1.0 g/d for the weight below 49 kg, in two divided doses. Prednisone was ad- ministrated as per ruler of each center. ResultsObservation termination was 3 months. Morbility of actue rejection was 3.40% (2/58)and 13.6% (3/22) in experimental and control group(P>0.05). Ad-verse events including hypertension, hyperlipemia, hyperglycemia and slight abnormality of liver func-tion occurred in 36. 2%(21/58) and 36. 4% (8/22) cases of experimental and control group(P> 0. 05). The survival rate in the 2 groups was 100%. The dose of tacrolimus in experimental group was significantly lower than that in the control group at 8 and 12 weeks posttransplant, while drug valley concentration in serum was proximal in 2 groups during the whole observation period.Conclusion Domestic tacrolimus capsules can be used effectively and safely in the management of acute rejection in renal transplantation.

Objective To investigate the effect of umbilical cord blood dendritic cells(DCs)induced by gastric cancer antigen combined with cytokine induced killer(CIK)cells in gastric cancer cell lines SGC-7901 in vitro. Methods Mononuclear cells from umbilical cord blood were used to create DCs and CIKs. The cell surface antigen expression of the mature DCs such as CD83,CD86,CD11c and the cell surface antigen of CIKs such as CD3,CD56,CD4,CD8,CD16 were detected using flow cytometry. Sensitized DCs-CIKs,DCs-CIKs,CIKs as effective cells,and SGC-7901 as target cells,the killing activities of these effective cells were tested with LDH release,which the number ratio of cells between effective cells and SGC-7901 cells were 10 :1,20 : 1,40 : 1,respectively. Results The cell surface antigen expressions of the mature DCs,such as CD83 + CD86 + ,CD11c + CD83 + ,CD86 + CD11c + were(75. 4 ± 2. 1)% ,(79. 3 ± 1. 4)% ,(80. 2 ± 2. 6)% , respectively. The mature sensitive-DCs surface antigen expressions,such as CD83 + CD86 + ,CD11c + CD83 + , CD86 + CD11c + ,were(77. 7 ± 1. 5)% ,(82. 6 ± 1. 9)% ,(76. 9 ± 2. 6)% ,respectively. There was no sta-tistical significance about the surface antigen expression between DCs and sensitive-DCs(t = 1. 526,P ﹥ 0. 05;t = 0. 958,P ﹥ 0. 05;t = 1. 049,P ﹥ 0. 05). The CIKs surface antigen expressions,such as CD4 + ,CD8 + , CD3 + CD56 + CD16 + ,were(22. 8 ± 1. 3)% ,(77. 3 ± 1. 8)% ,(24. 5 ± 2. 1)% ,respectively. The results suggested that the killing effect of the three kinds of combination cells on gastric cancer cells was different. The number ratio of cells between sensitive-DCs and SGC-7901 cells were 10 : 1,20 : 1,40 : 1,which the killing activities of sensitive-DCs-CIKs against SGC-7901 were(37. 68 ± 1. 49)% ,(41. 67 ± 0. 90)% ,(42. 71 ± 0. 98)% ,respectively. The killing activity of sensitive-DCs-CIKs was the highest when the ratio of cells between sensitive-DCs and SGC-7901 cells were 40 : 1. The killing activities of DC-CIKs were(36. 77 ± 0. 46)% ,(38. 94 ± 0. 95)% ,(41. 15 ± 0. 89)% ,respectively. The killing activities of CIKs were(34. 74 ± 1. 01)% ,(37. 76 ± 0. 43)% ,(39. 65 ± 0. 79)% ,respectively. There were statistically significant differences among the three groups(F = 5. 92,P ﹤ 0. 05;F = 19. 13,P ﹤ 0. 05;F = 8. 88,P ﹤ 0. 05). Conclusion The tumor killing activity of CIK is enhanced obviously by umbilical cord blood DCs which is sensitized by gastric cancer tumor antigen. There is the highest killing activity when the number ratio of cells between sensitive-DC-CIK and SGC-7901 cells is 40 : 1.

OBJECTIVETo study the effects of continuous passive motion on the tendon-bone healing of the semi-tendinous tendon autograft used for anterior cruciate ligament (ACL) reconstruction in rabbits.

METHODSIn 12 healthy 8-month-old male rabbits, an ACL reconstruction was performed by using double semi-tendinous tendon autograft. Postoperatively these animals were treated by either continuous passive motion (CPM) or cage activity. Specimens of the grafts were collected at 6, 12, 24 weeks postoperatively. Histological change in the tendon-bone healing was studied by haematoxylin-eosin and toluidine blue.

RESULTSThere was more new fiber tissue in the anterior half of the interface. Osteoclasts were most numerous at the tunnel aperture and in the anterior half of the interface. Cartilage in the tendon-bone interface was localized to the posterior aspect of tunnels, the area where compressive stress would be predicted. CPM group developed a denser connective tissue with less vascularity and cellularity. The bone tunnel had more areas with ingrowing denser connective tissue compared with cage activity specimens. With the growth of Sharpery's fibers and fibrocartilage into the interface, a direct ligament insertion was found. In the CPM specimens, the interface tissue was more mature and the direct insertion was broader and more structured.

CONCLUSIONSCompressive stress promotes chondroid formation, and the tension promotes fiber formation. Tendon-bone healing may be optimized by CPM after tendon transplantation into a bone tunnel.

Animals ; Anterior Cruciate Ligament ; surgery ; Femur ; pathology ; surgery ; Male ; Motion Therapy, Continuous Passive ; Rabbits ; Random Allocation ; Tendons ; pathology ; transplantation ; Tibia ; pathology ; surgery ; Transplantation, Autologous ; Wound Healing

Objective:To investigate the risk factors of bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants with gestational age ≤32 weeks within 28 days after birth and to establish and validate the nomogram model for BPD prediction.Methods:We retrospectively chose VLBW infants with gestational age ≤32 weeks who survived to postmenstrual age (PMA) 36 weeks and were admitted to the neonatal intensive care unit of Peking University Third Hospital from January 2016 to April 2020 as the training cohort. BPD was diagnosed in accordance with the 2018 criteria. The clinical data of these infants were collected, and the risk factors of BPD were analyzed by Chi-square test, Mann-Whitney U test, and multivariate logistic regression, and a nomogram model was established. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the predictive performance. Decision curve analysis (DCA) was constructed for differentiation evaluation, and the calibration chart and Hosmer-Lemeshow goodness of fit test were used for the calibration evaluation. Bootstrap was used for internal validation. VLBW infants with gestational age ≤32 weeks survived to PMA 36 weeks and admitted to Hebei Chengde Maternal and Child Health Hospital from October 2017 to February 2022 were included as the validation cohort. ROC curve and calibration plot were conducted in the validation cohort for external validation. Results:Of the 467 premature infants included in the training cohort, 104 were in the BPD group; of the 101 patients in the external validation cohort, 16 were in the BPD group. Multivariate logistic regression analysis showed that low birth weight ( OR=0.03, 95% CI: 0.01-0.13), nosocomial pneumonia ( OR=2.40, 95% CI: 1.41-4.09), late-onset sepsis ( OR=2.18, 95% CI: 1.18-4.02), and prolonged duration of endotracheal intubation ( OR=1.61, 95% CI: 1.26-2.04) were risk factors for BPD in these groups of infants (all P<0.05). According to the multivariate logistic regression analysis results, a nomogram model for predicting BPD risk was established. The AUC of the training cohort was 0.827 (95% CI: 0.783-0.872), and the ideal cut-off value for predicted probability was 0.206, with a sensitivity of 0.788 (95% CI: 0.697-0.862) and specificity of 0.744 (95% CI: 0.696-0.788). The AUC of the validation cohort was 0.951 (95% CI:0.904-0.999). Taking the prediction probability of 0.206 as the high-risk threshold, the sensitivity and specificity corresponding to this value were 0.812 (95% CI: 0.537-0.950) and 0.882 (95% CI: 0.790-0.939). The Hosmer-Lemeshow goodness-of-fit test in the training and validation cohort showed a good fit ( P>0.05). DCA results showed a high net benefit of clinical intervention in very preterm infants when the threshold probability was 5%~80% for the training cohort. Conclusion:Low birth weight, nosocomial pneumonia, late-onset sepsis, and prolonged tracheal intubation duration are risk factors for BPD. The established nomogram model has a certain value in predicting the risk of BPD in VLBW less than 32 weeks.

Objective To document the impact of conversion to mycophenolate mofetil (MMF)at different time points after transplantation on the renal function of renal function.Methods A longterm,multicenter,non-interventional and observational study was done.Two cohorts were included:One was Switch cohort (340 cases) including renal allograft recipients who switched to MMF at least 6 months after renal transplantation and followed up for 4 years after switch; The other was Stay cohort (123 cases),including renal allograft recipients who received MMF treatment after transplantation and followed up for 4 years after enrollment.Results GFR values of patients in Switch cohort was significantly increased after switch,and the change in GFR slope was 3.1 mL· min-1 · year-1 (P＜0.01).GFR values of patients in Stay cohort kept steady before and after enrollment,and the change in GFR slope was 0.44 mL·min-1 ·year-1 (P＞0.05).Statistically significant difference in the onset time of GFR decline (defined as 20％ decline from the baseline) was observed among subgroups within Switch cohort (P＜0.01),but there was no significant difference among subgroups within Stay cohort (P＞0.05).Stay cohort was 12％ higher than in Switch cohort every year.Conclusion Conversion to MMF ＞6 months or even many years after transplantation can obviously improve the renal function of recipients.The earlier conversion can benefit improvement of the renal function.

OBJECTIVE: To investigate the effect and possible mechanism of hydroxysafflor yellow A (HSYA) on human immortalized keratinocyte cell proliferation and migration. METHODS: HaCaT cells were treated with HSYA. Cell proliferation was detected by the cell counting kit-8 assay, and cell migration was measured using wound healing assay and Transwell migration assay. The mRNA and protein expression levels of heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF), EGF receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), and hypoxia-inducible factor-1α (HIF-1α) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. Circ_0084443-overexpressing HaCaT cells and empty plasmid HaCaT cells were constructed using the lentiviral stable transfection and treated with HSYA. The expression of circ_0084443 was detected by qRT-PCR. RESULTS: HSYA (800 µmol/L) significantly promoted HaCaT cell proliferation and migration (P<0.05 or P<0.01). It also increased the mRNA and protein expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and increased the phosphorylation levels of PI3K and AKT (P<0.05 or P<0.01). Furthermore, HSYA promoted HaCaT cell proliferation and migration via the HBEGF/EGFR and PI3K/AKT/mTOR signaling pathways (P<0.01). Circ_0084443 attenuated the mRNA expression levels of HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α (P<0.05). HSYA inhibited the circ_0084443 expression, further antagonized the inhibition of circ_0084443 on HBEGF, EGFR, PI3K, AKT, mTOR and HIF-1α, and promoted the proliferation of circ_0084443-overexpressing HaCaT cells (P<0.05 or P<0.01). However, HSYA could not influence the inhibitory effect of circ_0084443 on HaCaT cell migration (P>0.05). CONCLUSION HSYA played an accelerative role in HaCaT cell proliferation and migration, which may be attributable to activating HBEGF/EGFR and PI3K/AKT signaling pathways, and had a particular inhibitory effect on the keratinocyte negative regulator circ_0084443.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinase ; Phosphatidylinositol 3-Kinases/metabolism* ; ErbB Receptors/genetics* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; RNA, Messenger/genetics* ; Cell Movement ; Cell Line, Tumor ; Chalcone/analogs & derivatives* ; Quinones

Objective To explore the feasibility and safety of non-gastrointestinal decompression after esophagectomy and the necessity of gastric tube or the time to remove gastric tube. Methods Thirty patients with esophageal cancer who underwent surgical treatment in the Department of Thoracic and Cardiovascular Surgery, Nanjing Drum Tower Hospital, were included in the trial from June to October 2017. The patients were randomly and equally assigned to a trial group (non-gastrointestinal decompression) or a control group (gastrointestinal decompression). There was no significant difference in age (P=1.000), sex (P=1.000), tumor location (P=0.732), pathological type (P=1.000), pathological stage (P=0.507), and operation time (P=0.674) between the two groups. The clinical effect between the two groups were compared. Results There was no statistical difference in incidences of anastomotic leakage (P=1.000), anastomotic bleeding (P=1.000), gastroesophageal reflux (P=1.000) between the two groups. And there was no statistical difference in time of the first flatus (P=0.629) and the first bowel movement (P=0.599) after operation between the two groups. Conclusion Without gastrointestinal decompression after Ivor Lewis esophagectomy does not increase the incidences of anastomotic leakage, anastomotic bleeding and gastroesophageal reflux, and has no significant effect on the recovery of gastrointestinal function. Without gastrointestinal decompression after Ivor Lewis esophagectomy is safe and feasible. Removing gastric tube on the second day after operation is reasonable and feasible.

OBJECTIVE: To analyze the effects of visual restoration after cataract surgery on plantar pressure and biomechanics of foot in elder individuals. METHODS: Thirty-two patients [male/female 5/27, (70.1±5.2) years old] with age-related cataract were recruited between October 2016 and December 2019. The footscan system was employed to record the data of plantar pressure during level walking before and 1-month after the cataract surgery. Parameters of peak pressure (PP), impulse (I), pressure-time integral (PTI) and time to peak pressure (TPP) from the regions of the 1st toe (T1), 2nd to 5th toes (T2-5), 1st to 5th metatarsal heads (M1-M5), midfoot (MF), medial hindfoot (HM) and lateral hindfoot (HL) were analyzed respectively. RESULTS: Post-operatively, the visual function was effectively reconstructed with improved visual acuity in both eyes (Z=-4.878, -4.801; P < 0.001). The PP (t=2.266, P=0.031) and I (t=2.152, P=0.039) values in M2 region on the dominant side (right foot) increased statistically at post-operative phase, while the changes of pressure and temporal para-meters in other regions remained stable. There was laterality in plantar pressure at pre-operative phase, manifested as greater PP values in M1, M2, MF, and HM regions on the dominant sides (t=-2.414, -2.478, -2.144, -5.269; P < 0.05), greater PP values in T1, M3, M5 and HL regions on the non-dominant sides (t=4.830, 3.155, 2.686, 3.683; P < 0.05), greater I values in M1, MF, and HM regions on the dominant sides (t=-2.380, -2.185, -5.320; P < 0.05) and greater I values in T1, M3, M5 and HL regions on the non-dominant sides (t=4.489, 2.247, 2.838, 3.992; P < 0.05). post-operatively, the pressure tended to be compatible between the two sides in regions of M3 and MF, while the magnitude of laterality in regions of M1 (Z_PP△= -2.721, P=0.007; Z_I△=-2.581, P=0.010), M2 (Z_PP△=-2.674, P=0.007; Z_I△=-2.375, P=0.018) and M5 (Z_PP△=1.991, P=0.046; Z_I△=2.150, P=0.032) was further increased. CONCLUSION Changes in plantar pressure after cataract surgery were characterized as increased pressure in the 2nd metatarsal head area on the dominant side. Visual restoration might intensify the laterality in the medial of forefoot on the dominant side and the lateral of forefoot on the non-dominant side.
Aged ; Biomechanical Phenomena ; Female ; Foot ; Humans ; Male ; Middle Aged ; Pressure

Daphnetin is quickly eliminated in rats after dosing, but the mechanism remains unclear. This study was aimed to investigate the in vitro metabolism of daphnetin using rat liver S9 fractions (RLS9). The metabolites formed in RLS9 were identified and the kinetic parameters for different metabolic pathways were determined. HPLC-DAD-MS analysis showed that daphnetin was biotransformed to six metabolites, which were identified as 7 or 8 mono-glucuronide and mono-sulfate, 8-methylate, and 7-suflo-8-methylate. Methylation and glucuronidation of daphnetin exhibited the Michaelis-Menten kinetic characteristics, whereas the substrate inhibition kinetic and the two-site kinetic were observed for 8-sulfate and 7-sulfate formations. Of the 3 conjugation pathways, the intrinsic clearance rate for sulfation was highest, followed by methylation and glucuronidation. By in vitro-in vivo extrapolation of the kinetic data measured in RLS9, the hepatic clearance were estimated to be 54.9 mL·min^-1·kg^-1 which is comparable to the system clearance (58.5 mL·min^-1·kg^-1) observed in rats. In conclusions, the liver might be the main site for daphnetin metabolism in rats. Sulfation, methylation and glucuronidation are important pathways of the hepatic metabolism of daphnetin in rats.