Objective:To investigate the toxic effect of chlorambucil combined with ibrutinib on mantle cell lymphoma(MCL)cell line Jeko-1 and its related mechanism.Methods:The MCL cell line Jeko-1 was incubated with different concentrations of chlorambucil or ibrutinib or the combination of the two drugs,respectively.CCK-8 assay was used to detect the proliferation of the cells,and Western blot was used to measure the protein expression levels of BCL-2,caspase-3,PI3K,AKT and P-AKT.Results:After Jeko-1 cells were treated with chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibrutinib(3.125,6.25,12.5,25,50 μmol/L)alone for 24,48,72h respectively,the cell proliferation was inhibited in a time-and dose-dependent manner.Moreover,the two drugs were applied in combination at low doses(single drug inhibition rate＜50％),and the results showed that the combination of two drugs had a more significant inhibitory effect(all P＜0.05).Compared with the control group,the apoptosis rate of the single drug group of chlorambucil(3.125,6.25,12.5,25,50 μmol/L)and ibutinib(3.125,6.25,12.5,25,50 μmol/L)was increased in a dose-dependent manner.The combination of the two drugs at low concentrations(3.125,6.25,12.5 μmol/L)could significantly increase the apoptosis rate compared with the corresponding concentration of single drug groups(all P＜0.05).Compared with control group,the protein expression levels of caspase-3 in Jeko-l cells were upregulated,while the protein expression levels of BCL-2,PI3K,and p-AKT/AKT were downregulated after treatment with chlorambucil or ibrutinib alone.The combination of the two drugs could produce a synergistic effect on the expressions of the above-mentioned proteins,and the differences between the combination group and the single drug groups were statistically significant(all P＜0.05).Conclusion:Chlorambucil and ibrutinib can promote the apoptosis of MCL cell line Jeko-1,and combined application of the two drugs shows a synergistic effect,the mechanism may be associated with the AKT-related signaling pathways.

OBJECTIVE: To investigate efficacy between arthroscopic popliteal cyst drainage and arthroscopic popliteal cyst resection. METHODS: From January 2013 to June 2021, 54 patients with popliteal cyst (Rausching-Lindgren gradeⅠto Ⅲ) were treated with arthroscopic surgery. There were 24 males and 30 females. The age ranged from 44 to 72 years old, with a mean of (62.67±6.08) years old. The course of the disease ranged from 1 to 72 months, with a mean of(15±14) months. Twenty-four patients (group A) were underwent arthroscopic internal drainage of popliteal cyst. Thirty patients (group B) were underwent arthroscopic resection of popliteal cyst. Preoperative main symptoms included knee pain, swelling, walking pain, popliteal swelling, popliteal mass and so on. After 1, 3, 6 months and 1, 2 years of surgery, routine outpatient follow-up was conducted to observe and compare the surgical time, bleeding volume, preoperative and postoperative visual analog scale (VAS), knee Lysholm score, and complications between two groups. RESULTS: All incisions healed at one stage after operation. All 54 patients were followed up, and the duration ranged from 6 months to 2 years, with an average of (13.89±4.29) months. There was no intraoperative vascular or nerve injury. Operation time and intraoperative blood loss of the two groups:group A of (62.08±9.55) min and (8.00±1.69) ml, group B of (69.50±6.99) min and (8.70±2.00) ml. Popliteal pain, swelling, limitation of flexion and extension were significantly relieved after operation. VAS before and one month after operation between two groups:group A of 5.38±1.21 and 2.63±0.71, group B of 5.60±1.26 and 2.80±0.81. Lysholm scores of knee joint before and 6 months after operation:group A of 62.59±4.99 and 89.74±2.90, group B of 63.87±3.23 and 89.02±2.35. Knee joint function improved significantly in both groups. In group A, 4 cases had popliteal cyst at 3 months after operation, and 2 cases had small isolated cyst at 1 year after operation. There was no recurrence of cyst in group B. CONCLUSION The results between two arthroscopic treatments of popliteal cyst are satisfactory, and there is no significant difference in the amount of blood loss, safety, postoperative pain VAS score and knee function recovery. It is suggested that arthroscopic resection of the cyst wall should be performed when the technique is mature, especially for large cysts and septal cysts.
Female ; Male ; Humans ; Adult ; Middle Aged ; Aged ; Popliteal Cyst/surgery* ; Drainage ; Cysts ; Knee Joint/surgery* ; Pain

Animals ; Schistosoma japonicum ; Colitis, Ulcerative

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

  Objective  To explore the phenotype-genotype correlation of Alport syndrome in children.  Methods  Retrospectively analyze the clinical and pathological features of 55 patients with Alport syndrome with COL4A mutations detected by second-generation sequencing, who were treated at Beijing Children's Hospital from January 2016 to December 2020.  Results  A total of 55 children with Alport syndrome were included. All cases had hematuria, including 31 cases (56.4%) with gross hematuria and 24 cases (43.6%) with microscopic hematuria. A total of 39 (70.9%) patients also had proteinuria. Extrarenal manifestations were pres- ent in 12 patients (21.8%). 36(65.4%) patients had a family history of Alport syndrome. 32 patients underwent pathological examination and 23 of them had the specific pathological changes of Alport syndrome. In 55 cases, 36 (65.4%) were diagnosed as X-linked Alport syndrome, 5(9.1%) were diagnosed as autosomal recessive Alport syndrome, 10(18.2%) were diagnosed as autosomal dominate Alport syndrome, and 4(7.3%) were diagnosed as digenic Alport syndrome. Missense mutations in COL4A genes accounted for 62.5%, 67.5% of missense mutations resulted in glycine substitution. There were statistical significances in proteinuria degree and hearing loss between male and female patients with XLAS (P < 0.05) as well as statistical significance in the degree of proteinuria between autosomal recessive Alport syndrome and autosomal dominate Alport syndrome (P=0.044), and there was critical statistical significance in the age of onset. There was statistical significance in hearing loss between children with renal impairment and children with normal renal function (P=0.001).  Conclusions  Most of the pathogenic variants in COL4A genes that cause Alport syndrome result in glycine substitutions. The degree of proteinuria and hearing loss of males with XLAS were greater than those of females. The degree of proteinuria in autosomal recessive Alport syndrome was greater than that of children with autosomal dominate Alport syndrome, and the age of onset was earlier than that of autosomal dominate Alport syndrome. Renal manifestation was more severe in children with hearing loss. The early clinical manifestations of Alport syndrome are diverse and pathological manifestations may be atypical. The application of next-generation sequencing can reduce misdiagnosises of Alport syndrome.

OBJECTIVE: To explore clinical effect of lateral locking compression plate combined with medial buttress plate in treating osteoporotic comminuted fractures of proximal humerus. METHODS: From May 2017 to December 2021, 12 patients with osteoporotic comminution of proximal humerus were treated by lateral locking compression plates combined with medial buttress plates, including 5 males and 7 females, aged from 55 to 78 years old, bone mineral density(BMD) less than -2.5 g/cm3, the time from injury to operation was from 2 to 6 days. According to Neer classification, 7 patients were type Ⅲ, 4 patients were type Ⅳ and 1 patient was type Ⅵ. Postoperative complications, fracture healing and internal fixation were observed and Constant-Murley score of shoulder joint was used to evaluate clinical effects at 6 months after operation. RESULTS: Postoperative wound healed well at stage I. All patients were followed up from 6 to 18 months. Humeral head collapse and necrosis occurred in 1 patient and humeral head varus in 1 patient. No impact of shoulder joint, internal fixation loosening occurred. Constant-Murley score at 6 months ranged from 45 to 90 points, and 6 patients got excellent result, 3 good, and 3 poor. CONCLUSION Locking compression plate combined with medial buttress plate could effectively reconstruct medial humeral column support and enhance fracture stability, and receive satisfactory clinical results. However, no control group was established in this study, and function of shoulder joint has not been evaluated many times after operation, so it cannot dynamically reflect changes of shoulder joint function.
Aged ; Female ; Humans ; Male ; Middle Aged ; Bone Plates/adverse effects* ; Fracture Fixation, Internal/methods* ; Fractures, Comminuted/surgery* ; Humeral Fractures/complications* ; Humeral Head ; Humerus ; Shoulder Fractures/surgery* ; Treatment Outcome ; Osteoporotic Fractures/surgery*

Purpose: Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC. Materials and Methods: Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis. Results: Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC. Conclusion The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

The novel coronavirus is a newly discovered pathogen in late December 2019, and its source is currently unknown, which can lead to asymptomatic infection, new coronavirus pneumonia or serious complications, such as acute respiratory failure. Corona virus disease 2019 (COVID-19) is a new type of respiratory disease that is currently spreading all over the world and caused by this coronavirus. Its common symptoms are highly similar to those of other viruses, such as fever, cough and dyspnea. There is currently no vaccine or treatment for COVID-19. Everyone is susceptible to infection with this disease, and owing to the long-term use of immunosuppressants, the immunity of kidney transplant recipients is suppressed, and it is more likely to be infected with the disease. At present, its impact on kidney transplant recipients is unclear. This article reports the clinical features and therapeutic course of novel coronavirus infection in a patient after renal transplantation. A 37-year-old female patient who received a kidney transplant 6 months before was diagnosed with novel coronavirus pneumonia. The patient's symptoms (such as fever, chills, dry cough, muscle aches), laboratory tests (such as decreased white blood cell count, elevated liver enzymes and D-dimer, positive viral nucleic acid test), and chest CT (multiple left lower lung plaque ground glass shadow) were similar to those of non-transplanted novel coronavirus pneumonia patients. In terms of treatment, because the immunity of kidney transplant recipients has been suppressed for a long time, it is a very common strategy to suspend the use of immunosuppressive agents. Therefore, the patient immediately discontinued the immunosuppressive agent after admission, so that she could restore immunity against infection in a short time. At the same time, the use of glucocorticoids was also very important. Its immunosuppressive and anti-inflammatory effects played a large role in the treatment process.In addition, prophylactic antibiotics was needed, and nephrotoxic drugs should be used with caution. Finally, following discounting the use of immunosuppressant and a low-dose glucocorticoid-based treatment regimen, COVID-19 in this renal transplant recipient was successfully cured. The cure of this case was of great significance, and this adjuvant nonspecific antiviral therapy could provide a template for the treatment of other such patients.
Adult ; Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Female ; Humans ; Kidney Transplantation ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2 ; Transplant Recipients

Objective:To investigate the protective effect of Wutou Chishizhi Wan on myocardial ischemia reperfusion injury （MIRI） in rats， and observe its effect on such mechanisms as coagulation function， vascular endothelial cells and oxidative stress in rats. Method:A total of 40 SD rats were randomly divided into normal group， model group， positive drug group （Urokinase group） and Wutou Chishizhi Wan group， with 10 rats in each group. Except for the normal group， rat myocardial ischemia-reperfusion injury models were established. The changes of heart rate （HR） at 10 min before ischemia， 30 min after ischemia and 30， 60， 120 min （T₀，T₁，T₂，T₃，T₄）， and the change of electrocardiogram （ECG） J point after modeling in rats were observed. The pathological changes of rat myocardial tissue were observed by hematoxylin-eosin （HE） staining. The changes of four indexes of coagulation ［prothrombin time （PT）， activated partial thromboplastin time （APTT）， thrombin time （TT）， fibrinogen content decreased significantly （FIB）］ in rats were observed. The contents of endothelin-1 （ET-1）， thromboxane A₂ （TXA₂） and prostacyclin （PGI₂） in serum and myocardium levels of superoxide dismutase （SOD）， malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） of MIRI rats were observed. Western blot assay was used for the detection of oxidative stress protein Keap1 and transcription factor-E2-related factor （Nrf2） expression levels in rat myocardial tissue. Result:Compared with the normal group， the ECG of MIRI rats showed significant myocardial ischemic injury-like changes， ST segment was significantly elevated， J point was significantly increased， and the incidences of HR in T₁， T₂， T₃ and T₄ were significantly reduced （P<0.05， P<0.01）. Compared with the model group， Wutou Chishizhi Wan significantly reduced ECG J-point changes in MIRI rats， while increased the incidence of HR in T₁， T₂， T₃ and T₄ （P<0.05， P<0.01）. Compared with the normal group， PT， APTT and TT in the model group were significantly shortened （P<0.01）， FIB content was significantly increased （P<0.01）， and the serum PGI₂ level decreased and TXA₂ and ET-1 levels increased significantly in the model group （P<0.01）. SOD content and GSH-Px activities of myocardial tissue in the model group were significantly reduced （P<0.01）， whereas the MDA content was increased （P<0.01）. Compared with the model group， PT of the Wutou Chishizhi Wan group was prolonged （P<0.05） and APTT slightly prolonged， TT significantly prolonged （P<0.01）， FIB content decreased （P<0.05）， serum PGI₂ increased （P<0.05）， TXA₂ and ET-1 decreased significantly in the Wutou Chishizhi Wan group （P<0.01）， myocardial MDA content decreased， and SOD content and GSP-Px activity increased significantly （P<0.01）. Meanwhile， the Wutou Chishizhi Wan group was able to activate the Keap1/Nrf2 signaling pathway， which significantly increased Nrf2 expression and significantly decreased Keap1 expression （P<0.01）. Conclusion:Wutou Chishizhi Wan group can protect myocardial injury in MIRI rats. The specific mechanism is to protect MIRI by regulating vascular endothelial cell homeostasis and oxidative stress levels and activating Keap1/Nrf2 signaling pathway.