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Chronic hepatitis B (CHB) is a chronic progressive disease caused by hepatitis B virus (HBV), and without timely and effective antiviral therapy, it will eventually develop into liver cirrhosis, liver failure or hepatocellular carcinoma (HCC). Early initiation of antiviral therapy can prevent or delay disease progression and greatly reduce the incidence rates of liver cirrhosis, liver failure, and HCC. Due to the limited efficacy of current antiviral drugs, the indications for antiviral therapy are mainly applicable to patients with positive HBV DNA and persistent ALT abnormality and some special populations with HBV infection. However, some patients who cannot reach the criteria for antiviral therapy may have insidious disease progression, leading to adverse clinical outcomes. Therefore, the guidelines and consensus statements in China and globally are constantly expanding the indications for antiviral therapy for CHB, so as to bring benefits to more patients.
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OBJECTIVE@#To explore the similarities and variations of biological phenotype and cytotoxicity of human umbilical cord blood natural killer cells (hUC- NK) after human umbilical cord blood-derived mononuclear cells (hUC-MNC) activated and expanded by two in vitro high-efficient strategies.@*METHODS@#Umbilical cord blood mononuclear cells (MNC) from healthy donor were enriched by Ficoll-based density gradient centrifugation. Then, the phenotype, subpopulations, cell viability and cytotoxicity of NK cells derived from Miltenyi medium (denoted as M-NK) and X-VIVO 15 (denoted as X-NK) were compared using a "3IL" strategy.@*RESULTS@#After a 14-day's culture, the contents of CD3-CD56+ NK cells were elevated from 4.25%±0.04% (d 0) to 71%±0.18% (M-NK) and 75.2%±1.1% (X-NK) respectively. Compared with X-NK group, the proportion of CD3+CD4+ T cells and CD3+CD56+ NKT cells in M-NK group decreased significantly. The percentages of CD16+, NKG2D+, NKp44+, CD25+ NK cells in X-NK group was higher than those in the M-NK group, while the total number of expanded NK cells in X-NK group was half of that in M-NK group. There were no significant differences between X-NK and M-NK groups in cell proliferation and cell cycle, except for the lower percentage of Annexin V+ apoptotic cells in M-NK group. Compared with X-NK group, the proportion of CD107a+ NK cells in M-NK group were higher under the same effector-target ratio (E∶T) (P<0.05).@*CONCLUSION@#The two strategies were adequate for high-efficient generation of NK cells with high level of activation in vitro, however, there are differences in biological phenotypes and tumor cytotoxicity.
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Humans , Fetal Blood , Killer Cells, Natural , T-Lymphocytes , Leukocytes, Mononuclear/metabolism , Cell Proliferation , CD56 Antigen/metabolismABSTRACT
Objective:To explore the relationship between serum lactate level and early prognosis after liver transplantation (LT) in children.Methods:Between January 1, 2018 and December 31, 2020, 675 pediatric LT recipients were recruited. Clinical data were retrospectively reviewed, early postoperative serum lactate level and clearance rate recorded and receiver operating characteristic (ROC) curve plotted for determining optimal cut-off values. The inter-group differences in early postoperative complications and patient/graft survival rates were compared.Results:According to ROC, blood lactate levels >1.99 mmol/L at 12 h postoperatively were associated with early postoperative graft loss (AUC 0.73, 95% CI: 0.62-0.84, P=0.01). Age and weight of recipients in high-level group were 7.17(5.70-10.40) month and 7.00(6.00-8.60) kg and both were significantly lower than those in low-level group [7.80(6.21-13.58) month and 7.20(6.45-9.00) kg]. The inter-group differences were statistically significant ( P=0.017, P=0.034). Blood plasma transfusion volume, red blood cell transfusion volume, portal vein pressure pre-closure, postoperative intensive care unit (ICU) stay, ventilator use time, early allograft dysfunction rate, early postoperative pulmonary infection rate and recipient mortality rate in high-level group were 400 (200-400) ml, 2.00 (2.00-4.00) U, (15.71±4.44) mmHg, 2.50(2.00-3.00) day, 3.81(2.47-8.50) hour, 22.95%(42/185), 16.76%(31/185) and 6.49%(12/185) respectively. The above values were significantly higher than those in low-level group 200(100-400) ml, 2.00 (2.00-3.00) U, (14.69±4.68) mmHg, 2.00(2.00-3.00) day, 3.53(2.34-6.12) hour, 14.69%(72/490), 11.02%(54/490) and 1.43%(7/490) respectively. The inter-group differences were statistically significant ( P<0.001, P=0.014, P=0.015, P=0.037, P=0.043, P=0.011, P=0.045 & P<0.001). The incidence of early postoperative acute cellular rejection was significantly lower in high-level group than that in low-level group [11.89%(22/185) vs 22.86%(112/490)]. The inter-group difference was statistically significant ( P=0.01). The 1/3-month cumulative survival rates of patient/graft were 94.6%, 94.1% and 92.4%, 91.4% in high-level group versus 99.2%, 98.6% and 99.0%, 98.4% in low-level group. There were significant inter-group differences ( P=0, P<0.000 1). With a rising level of lactate at 12 h postoperatively, risk of early graft loss and early recipient mortality spiked markedly ( P<0.05). Conclusions:Serum lactate level post-operation is a valid predictor of early prognosis after LT in children.
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Objective:To study the impact of donor left hepatic vein classification and the reconstruction methods on hepatic venous outflow obstruction (HVOO) after pediatric living-donor liver transplantation using left lateral liver segments.Methods:A retrospective study was performed on the clinical data of 653 children recipients who underwent living-donor liver transplantation with left lateral liver segments from January 2014 to December 2020 at Tianjin First Central Hospital. There were 309 males and 344 females, aged 7.0 (6.0, 10.0) months, with an age range of 3-121 months. Based on the left hepatic vein on preoperative donor enhancement CT as well as the intraoperative reconstruction methods, the recipients were divided into 3 groups: type Ⅰ group ( n=514), anastomosis using a single opening was performed directly between the donor and the recipient; type Ⅱ group ( n=118), angioplasty was performed on two adjacent recipient venous orifices before anastomosis, and type Ⅲ group ( n=21), an interposition vessel was anastomosed to two widely spaced openings or the two veins were anastomosed separately. The preoperative general status of the patient, postoperative HVOO incidences, and graft and recipient survival rates were compared among the three groups. The patients were followed up by outpatient reexamination or telephone. Results:Graft to recipient weight ratio in the type Ⅲ group was smaller than that in the type Ⅰ group and the type Ⅱ group ( P<0.05). For all the 653 patients, the incidence of postoperative HVOO was 4.59% (30/653), with the incidences of HVOO in the 3 groups of patients were 4.1% for the type Ⅰ group (21/514), 5.1% for the type Ⅱ group (6/118), and 14.3% for the type Ⅲ group (3/21), respectively. There was no significant difference among the groups ( P>0.05). The recipient cumulative survival rates at 1 and 3 years after surgery in the type I group were 97.8% and 97.0%, and the corresponding rates in the type Ⅱ group were 96.5% and 94.2%, and in the type Ⅲ group were 94.1% and 86.9%, respectively. There was a significant difference between the type Ⅰ and type Ⅲ groups ( P=0.048). The graft cumulative survival rates at 1 and 3 years in the type Ⅰ group were 97.4% and 96.9%, and the corresponding rates in the type Ⅱ group were 94.9% and 92.5%, and in the type Ⅲ group were 94.1% and 86.9%, respectively. The difference in the postoperative graft cumulative survival rates between the type Ⅰ group and type Ⅱ group was significant ( P=0.044). Conclusions:The anatomy of the left hepatic vein supplying the left lateral liver segment was highly variable, and the majority of the variations could be reconstructed. A reasonable reconstructive method could reduce the incidence of postoperative HVOO and improved the outcomes of the graft.
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Objective:To explore the effect of multiple intelligences theory combined with the analysis, design, development, implementation, and evaluation (ADDIE) model in surgical clinical practice teaching.Methods:A total of 100 residents trained in Department of Gastrointestinal Surgery of Heping Hospital Affiliated to Changzhi Medical College from July 2019 to April 2020 were randomly divided into the control group ( n=50) and the observation group ( n=50). The control group used the ADDIE model, and the observation group adopted the multiple intelligences theory combined with the ADDIE model. The teaching assessment of the two groups was compared, and the core competence, critical thinking ability, self-evaluation, and teaching satisfaction of the two groups were evaluated. SPSS 22.0 was used for Chi-square test and t-test. Results:The scores of basic knowledges of gastrointestinal surgery, surgical clinical thinking and case analysis, routine skills and operations, and the total scores in the observation group were higher than those in the control group ( P<0.05). The scores of professional knowledge and skills, patient safety and rights, scientific research and academic ability, professional ethics, teamwork, personal and professional development ability in the observation group were higher than those in the control group ( P<0.05). While, there was no significant difference in the mastering of knowledge between the two groups ( P>0.05). The four dimensions of learning interest, self-learning ability, innovation ability, and clinical thinking establishment in the observation group were higher than those in the control group ( P<0.05). Conclusion:Multiple intelligences theory combined with ADDIE model in surgical clinical practice teaching can improve the teaching assessment results, significantly enhance the core competence, stimulate the learning interest, cultivate the self-learning ability and innovation ability of residents, and help them to establish clinical thinking ability.
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Objective:To summarize the experience of treatment for chronic pancreatitis by analyzing the clinical information of 10 533 patients with chronic pancreatitis admitted to First Affiliated Hospital of Naval Medical University (Changhai Hospital) in the past 28 years.Methods:Clinical data including the age, sex, place of birth, admission time, admission age, admission department, discharge time, hospitalization times and treatment methods of chronic pancreatitis patients admitted to Changhai Hospital from January 1995 to February 2022 were analyzed retrospectively. The changes of chronic pancreatitis patients′ admission, demographic characteristics and treatment mode were summarized.Results:A total of 10 533 patients were analyzed, including 7 443 males (70.66%) and 3 090 females (29.34%), and male to female ratio was 2.41∶1. The average age of admission was (45.7±15.0) years. In terms of geographical distribution, East China was the largest, followed by North China and Northwest China. 10 533 patients were admitted for 19 920 times, and there were 18 156 times (91.14%) in gastroenterology department and 1 452 times (7.29%) in general surgery department. Patients in gastroenterology department were admitted for (1.88±1.45) times and the average length of hospitalization was (10.33±5.63) days. A total of 14 134 endoscopic retrograde cholangiopancreatography [(1.45±1.41) times per patient] were performed among 8 022 patients, and 13 882 pancreatic extracorporeal shock wave lithotripsy [(2.22±0.36) times per patient] were performed among 6 629 patients. In general surgery department, patients were admitted for (1.03±0.16) times and the average length of hospitalization was (14.90±9.00) days. 1 242 patients underwent surgical treatment. The ratio of endoscopic therapy to surgery increased from 0.12∶1 in 1995 to 15.72∶1 in 2021.Conclusions:The study shows that chronic pancreatitis was more common in middle-aged males in China, and the treatment modes of chronic pancreatitis in Changhai Hospital had changed from surgery to endoscopic therapy.
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Objective:To study the effects of naringenin on pancreatic fibrosis in the mouse model of chronic pancreatitis (CP) and its effects on the activation, proliferation and apoptosis of pancreatic stellate cells (PSCs).Methods:Eighteen C57BL/6 mice were randomly divided into control group, CP group and naringenin group, with 6 mice in each group. The CP mouse model was established by intraperitoneal injections of caerulein. Naringenin group was given naringenin (200 mg/kg/day) by gavage once a day from the first day of the fourth week of modeling process to the day before the killing; the control group and CP group were treated by gavage with an equivalent amount of drug solvent containing 0.5% sodium carboxymethyl cellulose (CMC-Na). Mice were killed 5 days after the last caerulein injection, and their pancreatic tissues were collected for hematoxylin-eosin staining and Sirius Red staining, pathological scoring and collagen sedimentation detection. Naringenin with different concentrations (0, 5, 10, 20, 50, 100, 150, 200 μmol/L) were used to intervene HPSC for 24 hours, and CCK-8 method was used to detect the cell activity. TGF-β1 recombinant protein (2 ng/ml) was used to induce PSCs for 1 hour (TGF-β1 stimulation group), and naringenin with low (50 μmol/L), middle (100 μmol/L) and high (150 μmol/L) concentration was used to intervene for 36 hours after TGF-β1 stimulation, respectively. Western Blotting was used to detect the expression of PSC activation related proteins FN and COL1A1, cell proliferation marker p21, anti-apoptotic protein Bcl-xL, pro-apoptotic protein Bax and Bid.Results:The pathological scores of pancreatic tissue [(7.33±1.15), (4.67±1.15)] and the percentage of collagen positive areas [(46±4), (28±2)%] in CP group and naringenin group were higher than those in the control group [0, (4±2)%]. However, these indexes in the naringenin group were lower than those in CP group, and the differences were all statistically significant (all P value <0.05). The relative expression of FN in control group, TGF-β1 stimulation group and low, medium and high naringenin group was 0.02, 0.76, 0.67, 0.34 and 0.07, respectively; the expression of COL1A1 in these groups was 0.51, 1.71, 1.34, 0.84 and 0.11. The expression of FN and COL1A1 in TGF-β1 stimulation group was significantly higher than that in control group, and the expression of FN and COL1A1 in low, medium and high naringenin group was significantly lower than that in TGF-β1 stimulation group, and the differences were all statistically significant (all P value <0.05). The expression of p21 in the above five groups was 0.87, 1.18, 1.27, 1.22 and 1.00. The expression of p21 in TGF-β1 stimulation group was higher than that in control group, and the expression of p21 in high naringenin group was obviously lower than that in TGF-β1 stimulation group, and the differences were all statistically significant (all P value <0.05). In addition, the expression of Bcl-xL in these groups was 2.09, 2.21, 2.38, 2.50 and 2.12; the expression of Bax was 0.98, 0.88, 0.98, 1.00 and 0.88; the expression of Bid was 1.15, 1.09, 1.14, 1.18 and 1.18. There was no statistically significant difference among these groups (all P value >0.05). Conclusions:Naringenin could significantly alleviate the inflammation, atrophy and fibrosis in the CP mouse model, and inhibit the activation and proliferation of PSCs. However, naringenin had no significant effect on the apoptosis of PSCs, indicating that naringenin may be potentially used to treat pancreatic fibrosis in CP.
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Pruni Semen,the seed of several unique Prunus plants,is a traditional purgative herbal material.To determine the authentic sources of Pruni Semen,46 samples from four species were collected and analyzed.Ten compounds including multiflorin A(Mul A),a notable purative compound,were isolated and identified by chemical separation and nuclear magnetic resonance spectroscopy.Seventy-six communal components were identified by ultra-high performance liquid chromatography with linear ion trap-quadrupole Orbitrap mass spectrometry,and acetyl flavonoid glycosides were recognized as characteristic constituents.The flavonoids were distributed in the seed coat and cyanogenic glycosides in the kernel.Based on this,methods for identifying Pruni Semen from different sources were established using chemical fingerprinting,quantitative analysis of the eight principal compounds,hierarchical cluster analysis,principal component analysis,and orthogonal partial least squares discriminant analysis.The results showed that the samples were divided into two categories:one is the small seeds from Prunus humilis(Ph)and Prunus japonica(Pj),and the other is the big seeds from Prunus pedunculata(Pp)and Prunus triloba(Pt).The average content of Mul A was 3.02.6.93,0.40,and 0.29 mg/g,while the average content of amygdalin was 18.5,17.7,31.5,and 30.9 mg/g in Ph,Pj,Pp,and Pt,respectively.All the above information suggests that small seeds might be superior sources of Pruni Semen.This is the first comprehensive report on the identification of chemical components in Pruni Semen from different species.
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Objective: To explore the clinical effects of free transplantation of expanded thoracodorsal artery perforator flaps in reconstructing cervical cicatrix contracture deformity after burns. Methods: A retrospective observational study was conducted. From May 2018 to April 2021, 11 patients with cervical cicatrix contracture deformity after burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University, including 3 males and 8 females, aged 5 to 46 years, with a course of cervical cicatrix contracture deformity of 5 months to 8 years. The degree of cervical cicatrix contracture deformity was degree Ⅰ in one patient, degree Ⅱ in nine patients, and degree Ⅲ in one patient. In the first stage, according to the sizes of neck scars, one rectangular skin and soft tissue expander (hereinafter referred to as expander) with rated capacity of 200 to 600 mL was placed in the back. The expansion time was 4 to 12 months with the total normal saline injection volume being 3.0 to 3.5 times of the rated capacity of expander. In the second stage, free expanded thoracodorsal artery perforator flaps with areas of 10 cm×7 cm to 24 cm×13 cm were cut out to repair the wounds with areas of 9 cm×6 cm to 23 cm×12 cm which was formed after cervical cicatectomy. The main trunk of thoracodorsal artery and vein were selected for end-to-end anastomosis with facial artery and vein, and the donor sites were directly closed. The survival of flaps and healing of flap donor sites were observed on the 14th day post surgery. The appearances and cicatrix contracture deformity of the flaps, recovery of cervical function, and scar hyperplasia of donor sites were followed up. Results: On the 14th day post surgery, the flaps of ten patients survived, while ecchymosis and epidermal necrosis occurred in the center of flap of one patient and healed 2 weeks after dressing change. On the 14th day post surgery, the flap donor sites of 11 patients all healed well. During the follow-up of 6-12 months post surgery, the flaps of ten patients were similar to the skin around the recipient site in texture and color, while the flap of one patient was slightly swollen. All of the 11 patients had good recovery of cervical function and no obvious scar hyperplasia nor contracture in the flaps or at the donor sites. Conclusions: Application of expanded thoracodorsal artery perforator flaps can restore the appearance and function of the neck, and cause little damage to the donor site in reconstructing the cervical cicatrix contracture deformity after burns, which is worthy of clinical reference and application.
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Female , Humans , Male , Arteries , Burns/surgery , Cicatrix/surgery , Contracture/surgery , Hyperplasia , Perforator Flap , Plastic Surgery Procedures , Skin Transplantation , Soft Tissue Injuries/surgery , Treatment OutcomeABSTRACT
Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)μm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.
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Humans , Male , Biopsy/adverse effects , Cardiomegaly/pathology , Cardiomyopathy, Hypertrophic/diagnosis , Eosine Yellowish-(YS) , Fibrosis , Heart Defects, Congenital , Hematoxylin , Lipofuscin , Myocardium/pathology , Retrospective StudiesABSTRACT
Objective:To observe any effect of functional magnetic stimulation (FMS) of the sacral 3 nerve root on relieving urine retention after a spinal cord injury.Methods:Forty-four patients with neurogenic bladder disorders after a spinal cord injury were divided at random into a 5Hz group ( n=14), a 20Hz group ( n=15), and a sham stimulation group ( n=15). In addition to conventional bladder control training, the 5Hz and 20Hz groups were given 20 minutes of FMS of the sacral 3 nerve root at the appropriate frequency five days a week for 4 weeks. The sham stimulation group was not given any stimulation. A detailed urination diary was kept during the treatment, and before and after the 4 weeks, everyone′s bladder pressure volume was assessed and an electromyogram was recorded. Results:After the treatment those in the 5Hz and 20Hz groups had improved significantly in terms of average bladder capacity, bladder pressure, residual urine volume, daily number of urethral catheterizations, daily micturition frequency, single urine output, H-reflex latency, and the amplitude and incubation period of the F wave. Those in the sham stimulation group showed no consistent improvement in any of these indicators. Moreover, the average residual urine volume, daily urination frequency and H-reflex latency and amplitude of the 20Hz group were significantly better than those of the 5Hz group.Conclusions:Magnetic stimulation of the S3 nerve roots can effectively improve the urination of persons with neurogenic bladder disorders after a spinal cord injury. The preferred frequency is 20Hz.
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Objective:To observe the clinical efficacy of Shenqi Dihuang Decoction combined with conventional western medicine in the treatment of stage Ⅲ Diabetic Nephropathy (DN).Methods:A total of 96 patients with stage Ⅲ diabetic nephropathy with syndrome of deficiency of qi and yin in our hospital, from January 2019 to January 2021, who met the inclusion criteria, were divided into 2 groups by random number table method, 48 in each group. The control group was given the conventional western treatment. The observation group was given Shenqi Dihuang Decoction on the basic of the control group treatment. Both groups treatment lasted for 3 months. Before and after the treatment, the changes of TCM Syndrome Scores were observed. The levels of soluble intercellular adhesion molecular-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were detected by double antibody sandwich ELISA. The levels of BUN, SCr, SOD and Hcy were detected by automatic biochemical analyzer, collect 24-hour urine, 24-hour urine total protein quantity (24 UTP) was detected by immunoturbidimetry, and eGFR was calculated by CKD-EPI formula to evaluate the clinical efficacy.Results:After the treatment, the total effective rate in the observation group was 83.3% (40/48), and the control group was 66.7% (32/40) and the difference was statistically significant ( χ2=3.56, P=0.049). After the treatment, TCM Syndrome Scores in the observation group was significantly better than that of the control group ( t=4.05, P<0.01). After treatment, the systolic blood pressure in the observation group was significantly lower than that of the control group ( t=4.29， P<0.01). After treatment, the levels of 24 hUTP [(1.43 ± 0.54) g vs. (1.86 ± 0.50) g, t=4.05], serum sICAM-1[(396.07 ± 50.61)μg/L vs. (480.11 ± 63.01)μg/L, t=7.20], Hcy [(27.41 ± 3.42) μmol/L vs. (29.76 ± 5.80) μmol/L, t=2.42] in the observation group were significantly lower than those in the control group ( P<0.05), and the levels of SOD [(168.32 ± 41.26) U/ml vs. (143.11 ± 37.02) U/ml, t=3.15] was significantly higher than that of the control group ( P<0.01). Conclusions:Shenqi Dihuang Decoction combined with conventional western medicine can reduce 24 hUTP quantity and kidney damage, delay the development of Ⅲ DN, improve clinical effect and protect the kidney function, and sICAM-1 for the Ⅲ DN patients with the syndrome of qi and yin deficiency combined with blood stasis.
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Atopic dermatitis （AD） is a chronic， recurrent and inflammatory skin disease. Modern medical research suggests that AD is related to immune function， genes， skin barrier and other factors， while the specific etiology and pathogenesis remains unclear. The disease has a long course and is prone to reoccur， which seriously affects people’s production and life. Steroids， antihistamines and immunosuppressants are commonly used western medicines for the treatment of AD， which， however， will cause adverse reactions after long-term application. Traditional Chinese medicine （TCM） has a long history， good therapeutic effect and rich clinical experience in the prevention and treatment of AD， and the research on the treatment of AD with TCM has been intensifying. Centering on the theory of TCM， we systematically summarized the research progress related to AD， discussed the etiology and pathogenesis of AD， and summarized the TCM syndrome differentiation of AD from the aspects of eight principles， etiology， Qi-blood-body fluid， zang-fu organs， six meridians， defense-Qi-nutrient-blood and triple energizer. According to the etiology and pathogenesis of AD， we proposed the therapeutic regimens corresponding to the type and stage of the disease. Considering the research progress achieved in the recent years in the prevention and treatment of AD by TCM and the modern pharmacological research on Chinese medicinal materials， we reviewed the classic famous prescriptions， self-made prescriptions and Chinese patent medicines， and expounded the mechanisms of single Chinese medicinal materials in the treatment of AD at the molecular level. The TCM external therapies such as wet compress， medicated bath， gel and ointment are safe and effective. Acupuncture and moxibustion play a role in the prevention and treatment of AD， which is worthy of promotion in clinical practice， and the syndrome differentiation methods of Qi-blood-body fluid and triple energizer are novel in the treatment of this disease. TCM， characterized by diverse therapeutic methods and good clinical efficacy， is worthy of promotion in the treatment of AD， which will contribute to the development of TCM in China.
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Objective:To explore the risk factors of biliary complications(BCS)after pediatric living donor liver transplantation(LDLT).Methods:From January 2016 to December 2020, retrospective review of clinical data was performed for 681 children aged <18 years undergoing LDLT.There were 324 boys and 357 girls with a median age of 7.4 months and a median weight of 7.0 kg.Among 61 BCS patients(9.0%), there were biliary stricture(n=34, 5.0%), bile leakage(n=21, 3.1%)and bile leakage combined with biliary stricture(n=6, 0.9%). According to the absence or presence of BCS after LT, the recipients were divided into two groups of BCS(n=61)and non-BCS(n=620). The incidence and risk factors of BCS were analyzed.T-test, Wilcoxon rank sum test, Chi square or Fisher exact test was employed for univariate statistical analysis and Logistic regression for multivariate statistical analysis.Results:The median follow-up period was 35.5 months.Univariate analysis revealed statistically significant inter-group differences( P=0.005, 0.046, 0.009, 0.011, 0.024, 0.023, 0.004, 0.038, 0.002, 0.029, 0.023, 0.002, 0.011)in donor age[(31.4±5.7)vs.(34.3±7.5)years], time of anhepatic phase[43(37.0, 53.0)vs.47(38.8, 56.0)min], time from portal vein opening to hepatic artery opening[35(30.0, 41.0)vs. 38(30.8, 47.8)min], type of perfusion fluid, number of donor bile ducts, intestinal loop length[40(30.0, 40.0)vs.40(25.0, 40.0)cm], mode of biliary reconstruction, whether or not placing a support tube, incidence of hepatic artery thrombosis[1.6%(10/620)vs.9.8%(6/61)], incidence of abdominal infection[4.5%(28/620)vs.11.5%(7/61)], incidence of cytomegalovirus(CMV)infection[55.3%(343/620)vs.70.5%(43/61)], incidence of portal vein thrombosis[1.1%(7/620)vs.8.2%(5/61)]and incidence of pulmonary infection[19.0%(118/620)vs.32.8%(20/61)]. Multivariate analysis indicated that independent risk factors of BCS included donor age( P=0.023), number of donor bile ducts( P=0.017), time from portal vein opening to hepatic artery opening( P=0.010), hepatic artery thrombosis( P=0.004), abdominal infection( P=0.019), CMV infection( P=0.022), portal vein thrombosis( P=0.003), pulmonary infection( P=0.021)and short intestinal loop length( P=0.012). Conclusions:Biliary complications are common after pediatric LDLT.Independent risk factors are donor age, number of donor bile ducts, time from portal vein opening to hepatic artery opening, hepatic artery thrombosis, abdominal infection, CMV infection, portal vein thrombosis, pulmonary infection and short length of intestinal loop.
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Objective:To investigate the effects of different donor types on the prognosis of pediatric liver transplant recipients with low-body-weight (≤6 kg).Methods:The clinical data of low-body-weight pediatric liver transplant recipients from the Department of Pediatric Organ Transplantation, Tianjin First Central Hospital from January 2013 to June 2021 were retrospectively analyzed.The recipients were divided into living donor group, split donor group and whole liver group according to the donor type.The basic information of donors and grafts, preoperative and intraoperative information of recipients, major postoperative complications and survival rates of recipients and grafts were compared.Results:A total of 244 recipients were enrolled in this study, including 183 cases in the living donor group, 18 cases in the split donor group and 43 cases in the whole liver group.There were no statistical differences in the preoperative data of the three groups, including gender, age, body weight, blood type matching, primary disease, Child-pugh grading, and pediatric end-stage liver disease score (PELD). The incidence of hepatic artery thrombosis (HAT) in the three groups was 2.2%, 16.7% and 25.6%, respectively, the difference was statistically significant between the living donor group and the split donor group ( P=0.017) as well as the whole liver group ( P<0.001). There was no significant difference between the latter two groups ( P=0.525). The median follow-up time was 37, 31 and 47 months, respectively.The 1-year and 3-year cumulative graft survival rates were 92.9%, 91.3%, 83.3% and 83.3% 76.7%, 76.7% ( P=0.016), respectively.There was statistical difference between the living donor group and the whole liver group ( P=0.004), and no statistical difference between the split donor group and the living donor group ( P=0.212) as well as the whole liver group ( P=0.610). The 1-year and 3-year cumulative recipient survival rates in the three groups were 92.9%, 91.3%, 94.4% and 94.4%, 86.0%, 86.0%, respectively, and there was no statistical difference among the three groups ( P=0.463). Multivariate analysis suggested that donor age and anhepatic phase were independent risk factors for HAT.Cold ischemia time, volume of intraoperative blood transfusion and HAT were independent risk factors for early graft loss (within 3 months). The volume of intraoperative blood transfusion and the duration of anhepatic phase were independent risk factors for recipient death. Conclusions:Living donor liver transplantation is more effective than whole liver transplantation for children with low body weight (≤6 kg). Due to the small sample size and the early exploration stage of split liver transplantation in children, the efficacy of split liver transplantation remains to be explored in clinical practice.
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Objective:To explore the impact of graft recipient weight ratio(GRWR)on pediatric whole liver transplantation in infants aged under 1 year.Methods:From January 2014 to December 2019, clinical data were retrospectively reviewed for 140 children aged under 1 year with whole liver transplantation.They were divided into 3 groups of low GRWR(GRWR<2.5%, 48 cases), middle GRWR(2.5%≤GRWR<5%, 73 cases)and high GRWR(GRWR≥5%, 19 cases). Basic profiles, major postoperative complications and survival rate of graft/recipient were compared.Results:There were 62 males and 78 females with an average age of (7.34±1.81)months and an average weight of(6.81±1.09)kg.The median GRWR was 3.27%(1.33%~8.12%). The higher level of GRWR, the greater age, weight and graft weight of donor in three groups and there was statistical difference ( P<0.05); operative duration, postoperative ICU stay and hospital stay were longer in low GRWR group than those in middle GRWR group and there was statistical difference( P<0.05); The incidence of postoperative hepatic artery thrombosis was higher in low GRWR group than that in middle GRWR group(31.3%vs 8.2%)and there was statistical difference( P<0.05); 4 cases of small-for-size syndrome occurred in low GRWR group, it was significantly different from the other two groups and there was statistical difference( P<0.05); the median follow-up period was(50.7±23.4)months.The survival rates of grafts at 3-month and 1/5-year were 89.6%, 91.8%, 100%; 87.5%, 87.7%, 100%; 87.5%, 87.7%, 100%and there was no inter-group difference( P>0.05). The survival rates of recipients at 3 months, 1 year and 5 years post-operation were 93.8%, 91.8%, 100%; 91.7%, 87.7%, 100%; 91.7%, 87.7%, 100%and there was no inter-group difference( P>0.05). Conclusions:Different from pediatric living donor transplantation, GRWR≥5%does not affect the survival rate of recipient/graft during whole liver transplantation.And GRWR<2.5%may boost the postoperative incidence of hepatic artery thrombosis and small liver syndrome.
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The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.
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Lysine specific demethylase 1 (LSD1), a transcriptional corepressor or coactivator that serves as a demethylase of histone 3 lysine 4 and 9, has become a potential therapeutic target for cancer therapy. LSD1 mediates many cellular signaling pathways and regulates cancer cell proliferation, invasion, migration, and differentiation. Recent research has focused on the exploration of its pharmacological inhibitors. Natural products are a major source of compounds with abundant scaffold diversity and structural complexity, which have made a major contribution to drug discovery, particularly anticancer agents. In this review, we briefly highlight recent advances in natural LSD1 inhibitors over the past decade. We present a comprehensive review on their discovery and identification process, natural plant sources, chemical structures, anticancer effects, and structure-activity relationships, and finally provide our perspective on the development of novel natural LSD1 inhibitors for cancer therapy.
Subject(s)
Humans , Antineoplastic Agents/therapeutic use , Enzyme Inhibitors/therapeutic use , Histone Demethylases/metabolism , Lysine/therapeutic use , Neoplasms/drug therapyABSTRACT
Objective:To explore the efficacy of reduced left lateral segment graft during pediatric living donor liver transplantation.Methods:From January 2014 to December 2019, 67 children aged under 1 year underwent living donor liver transplantation with reduced left lateral segment graft (RLLS group). Clinical data were analyzed retrospectively and compared with those of left lateral segmentgraft living donor liver transplantation (LLS group). The differences in basic profiles, postoperative complications and postoperative patient/graft survival rate were compared.They were divided into two groups according to whether graft/recipient weight ratio (GRWR) was more than 4%.And major postoperative complications and graft/recipient survival rates were compared.Results:Age, height and weight of recipients were significantly lower in RLLS group than those in control group ( P<0.05). However, donor weight, donor body mass index (BMI), estimated graft volume and proportion of fatty liver from donor were significantly higher than those in control group ( P<0.05). Operative duration, intraoperative blood loss and erythrocyte transfusion were significantly higher than those in control group ( P<0.05). No significant inter-group differences existed in average postoperative hospital stay, intensive care unit (ICU) stay duration or postoperative ventilator use time ( P>0.05); no significant inter-group difference existed in the incidence of such major surgical complications as hepatic artery thrombosis, portal vein stenosis and bile duct complications ( P>0.05). The 1/3-year cumulative survival rates of postoperative patients and grafts were 92.5%, 91.2% and 92.5%, 91.2% in RLLS group and 96.3%, 95.3% and 95.9%, 95.1% in LLS group respectively.There was no significant inter-group difference ( P<0.05). The rate of postoperative hepatic vein stenosis was significantly higher in GRWR>4% group than that in control group ( P<0.05). Conclusions:Due to a rapid progress of technology, living donor liver transplantation has achieved satisfactory outcomes in children with reduced left lateral segment graft.Whether or not performing reduction surgery should be judged comprehensively according to the matching of donors and recipients and blood flow of liver during operations.And GRWR>4% is not an implementation criterion.
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Objective:To examine the incidence of lymphatic leakage after pediatric liver transplantation and explore the diagnosis and treatment of lymphatic leakage.Methods:From January 1, 2016 to December 31, 2019, clinical data were analyzed retrospectively for 805 pediatric liver transplant recipients. Based upon the diagnosis of lymphatic leakage, they were divided into two groups of lymphatic leakage ( n=271) and lymphatic non-leakage ( n=534). Analyzing the incidence of lymphatic leakage after liver transplantation in children, evaluating the treatment plan, comparing survival rate and the incidence of postoperative complications between two groups. Results:The incidence of lymphatic leakage was 33.7%(271/805); the proportion of partial liver donors was 14.8% in lymphatic leakage group and 25.8% in lymphatic non-leakage group ( P<0.001). Other basic profiles of two groups were not statistically different. The median follow-up period was 32 months in lymphatic leakage group and 30.6 months in lymphatic non-leakage group. No significant inter-group difference existed in cumulative survival rate, vascular complications, bile leakage, acute cell rejection or intestinal obstruction. The area-under-curve (AUC) of ascites to serum triglyceride (TG) ratio for predicting lymphatic leakage was 0.741, optimal cut-off value 0.54, sensitivity 59.2% and specificity 80.1%. Conclusions:Lymphatic leakage is a common complication after liver transplantation in children. With no significant correlation with the morbidity or mortality, it prolongs postoperative hospital stay. The ratio of ascites to serum TG may be utilized as an effective reference index for diagnosing lymphatic leakage. And lymphatic leakage can be improved by taking a low-fat diet.