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In this work, we report the synthesis of a new thiosemicarbazone-based drug of N'-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) featuring a thiazole spectator for efficient coordination with Cu(II) to give [CuCl(L)]2 (1) and [Cu(NO3)(L)]2 (2). Both 1 and 2 exhibit dimeric structures ascribed to the presence of di-2-pyridylketone moieties that demonstrate dual functions of chelation and intermolecular bridging. HL, 1, and 2 are highly toxic against hepatocellular carcinoma cell lines Hep-G2, PLC/PRF/5, and HuH-7 with half maximal inhibitory concentration (IC50) values as low as 3.26 nmol/mL (HL), 2.18 nmol/mL (1), and 2.54 × 10-5 nmol/mL (2) for PLC/PRF/5. While the free ligand HL may elicit its anticancer effect via the sequestration of bio-relevant metal ions (i.e., Fe3+ and Cu2+), 1 and 2 are also capable of generating cytotoxic reactive oxygen species (ROS) to inhibit cancer cell proliferation. Our preliminary pharmacokinetic studies revealed that oral administration (per os, PO) of HL has a significantly longer half-life t1/2 of 21.61 ± 9.4 h, nearly doubled as compared with that of the intravenous (i.v.) administration of 11.88 ± 1.66 h, certifying HL as an effective chemotherapeutic drug via PO administration.
Subject(s)
Antineoplastic Agents , Copper , Thiazoles , Thiosemicarbazones , Thiosemicarbazones/chemistry , Thiosemicarbazones/pharmacology , Thiosemicarbazones/pharmacokinetics , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Copper/chemistry , Thiazoles/chemistry , Thiazoles/pharmacology , Thiazoles/pharmacokinetics , Cell Line, Tumor , Biological Availability , Animals , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/pharmacokinetics , Administration, Oral , Molecular Structure , Hep G2 Cells , Reactive Oxygen Species/metabolismABSTRACT
OBJECTIVES: The goal of this project was to evaluate the effect of surgical treatment and the long-term survival of patients with staged IE/IIE pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: From January 2004 to December 2018, we retrospectively analysed 96 patients diagnosed with low-stage primary pulmonary MALT lymphoma according to the modified Ann Arbor staging system (IE/IIE). We compared the outcomes of different treatment modalities for staged IE/IIE MALT lymphoma. Progression-free survival (PFS) and overall survival were estimated using Kaplan-Meier curves, and the differences were compared using the log-rank test. The Cox proportional hazards model was used in this study. RESULTS: The median PFS time of low-staged MALT lymphomas was 118 months. The overall survival and PFS of the radical surgery group and the biopsy + chemotherapy group suggested no significant difference (P = 0.63, P = 0.65). Patients positive for Blc-2 and Ki-67 suffered from a compromised PFS (P = 0.023, P = 0.006). The Cox adjusted proportional hazards model analysis suggested that surgical procedures were not protective factors for patients with low-staged (IE/IIE) pulmonary MALT lymphoma, whereas being positive for Blc-2 and Ki-67 was a risk factor for patients with low-staged pulmonary MALT lymphoma (hazard ratio: 9.567; P = 0.044; hazard ratio: 6.042, P = 0.049). CONCLUSIONS: Our findings suggested that for staged IE/IIE pulmonary MALT lymphoma, radical surgical resection did not provide a survival benefit compared with chemotherapy after biopsy. Thus, radical surgery may be avoided unless biopsy is necessary for a diagnosis that requires sublobar resection. For those lesions that were Blc-2- or Ki-67-positive, compromised survival may be suggested.
Subject(s)
Lymphoma, B-Cell, Marginal Zone , Humans , Lymphoma, B-Cell, Marginal Zone/diagnosis , Lymphoma, B-Cell, Marginal Zone/drug therapy , Lymphoma, B-Cell, Marginal Zone/pathology , Retrospective Studies , Ki-67 Antigen , Neoplasm Staging , PrognosisABSTRACT
Accurate identification of the intersegmental plane is the key to successful segmentectomy. This case series included 41 patients who underwent uniportal thoracoscopic segmentectomy using the open insufflation method to identify the intersegmental plane for pulmonary nodules. The median age of the patients was 58 (range 35-73) years, and 63.4% were female. Malignant pulmonary nodules accounted for 80.5% of cases and were staged as 0-IA2. Seventeen patients underwent a single subsegmentectomy or single segmentectomy, and 24 underwent combined subsegmentectomy or subsegmentectomy combined with segmentectomy. There was no conversion to multiportal video-assisted thoracoscopic surgery, open surgery, or lobectomy. The median operative time was 84 (range 45-194) min, and the median blood loss was 50 (range 10-150) ml. The median chest tube duration and postoperative hospital stay were 2 (range 1 - 7) days. One (2.4%) developed an air leak for >5 days. No deaths occurred within 30 days after surgery.
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Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Subject(s)
HIV Infections , HIV-1 , Male , Humans , Middle Aged , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use , HIV Infections/drug therapy , Drug Resistance, Viral/genetics , China/epidemiology , Mutation , HIV-1/genetics , Protease Inhibitors/pharmacology , Protease Inhibitors/therapeutic use , GenotypeABSTRACT
Background: To share our experience of uniportal robotic-assisted thoracic surgery (U-RATS) anatomic pulmonary resection. Methods: A retrospective study was conducted to compare the efficacy of U-RATS and biportal-RATS (B-RATS; 2 ports). From March 2021 to June 2022, 109 patients were enrolled in this study. The perioperative results of U-RATS and B-RATS were compared. Results: Perioperative outcomes were comparable between the two groups, including the length of hospital stay and the rate of post-operative (post-op) complications. The mean duration of surgery of the two groups were 124.1 vs. 103.6 min (P=0.049), mean intraoperative blood loss was 131.7 vs. 143.1 mL, mean post-op hospital stay was 3.83 vs. 3.05 days (P=0.037), and the thoracic drainage of the first day after surgery were 230.9 vs. 207.1 mL. The visual analogue scale (VAS) scores after the first post-op day were 3.83 vs. 4.57 (P=0.018). No perioperative mortality occurred in either group. Conclusions: Both U-RATS and B-RATS are safe and feasible methods for major pulmonary resections. U-RATS achieved similar perioperative outcomes and lower VAS-scores for the patients, which may improve the post-op experience and the quality of patients' lives. Further follow-up investigations are required to evaluate the long-term efficacy of U-RATS.
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BACKGROUND: Prolonged mechanical ventilation (PMV), mostly defined as mechanical ventilation > 72 h after lung transplantation with or without tracheostomy, is associated with increased mortality. Nevertheless, the predictive factors of PMV after lung transplant remain unclear. The present study aimed to develop a novel scoring system to identify PMV after lung transplantation. METHODS: A total of 141 patients who underwent lung transplantation were investigated in this study. The patients were divided into PMV and non-prolonged ventilation (NPMV) groups. Univariate and multivariate logistic regression analyses were performed to assess factors associated with PMV. A risk nomogram was then established based on the multivariate analysis, and model performance was further examined regarding its calibration, discrimination, and clinical usefulness. RESULTS: Eight factors were finally identified to be significantly associated with PMV by the multivariate analysis and therefore were included as risk factors in the nomogram as follows: the body mass index (BMI, P = 0.036); primary diagnosis as idiopathic pulmonary fibrosis (IPF, P = 0.038); pulmonary hypertension (PAH, P = 0.034); primary graft dysfunction grading (PGD, P = 0.011) at T0; cold ischemia time (CIT P = 0.012); and three ventilation parameters (peak inspiratory pressure [PIP, P < 0.001], dynamic compliance [Cdyn, P = 0.001], and P/F ratio [P = 0.015]) at T0. The nomogram exhibited superior discrimination ability with an area under the curve of 0.895. Furthermore, both calibration curve and decision-curve analysis indicated satisfactory performance. CONCLUSION: A novel nomogram to predict individual risk of receiving PMV for patients after lung transplantation was established, which may guide preventative measures for tackling this adverse event.
Subject(s)
Idiopathic Pulmonary Fibrosis , Lung Transplantation , Humans , Respiration, Artificial/adverse effects , Retrospective Studies , Risk Factors , Idiopathic Pulmonary Fibrosis/etiology , Lung Transplantation/adverse effectsABSTRACT
Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ2=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Subject(s)
Male , Humans , Middle Aged , Reverse Transcriptase Inhibitors/therapeutic use , HIV Infections/drug therapy , Drug Resistance, Viral/genetics , China/epidemiology , Mutation , HIV-1/genetics , Protease Inhibitors/therapeutic use , GenotypeABSTRACT
Species within the Aspergillus spp. cause a wide range of infections in humans, including invasive pulmonary aspergillosis, chronic pulmonary aspergillosis, and allergic bronchopulmonary aspergillosis, and are associated with high mortality rates. The incidence of pulmonary aspergillosis (PA) is on the rise, and the emergence of triazole-resistant Aspergillus spp. isolates, especially Aspergillus fumigatus, limits the efficacy of mold-active triazoles. Therefore, host-directed and novel adjunctive therapies are required to more effectively combat PA. In this review, we focus on PA from a microbiome perspective. We provide a general overview of the effects of the lung and gut microbiomes on the growth of Aspergillus spp. and host immunity. We highlight the potential of the microbiome as a therapeutic target for PA.
Subject(s)
Gastrointestinal Microbiome , Pulmonary Aspergillosis , Antifungal Agents , Aspergillus , Aspergillus fumigatus , Humans , Lung , TriazolesABSTRACT
Background: Although orthotopic single lung transplantation in rats has long been established, this model is still highly challenging. Therefore, we made several modifications in anesthesia, lung extraction, vascular clamp, and transplantation procedures for this model. Methods: Fifty cases of rat left lung transplantation were performed using traditional procedures and modified surgical techniques, respectively. Two hundred Sprague Dawley male rats, half as donors and half as recipients, were randomized equally to the two groups. The modifications included orotracheal intubation via a video laryngoscope, retrograde perfusion following anterograde perfusion, a Rummel tourniquet for the occlusion of pulmonary vessels, flushing the vessels and cuffs before anastomosis with heparin, and a simple pleural drainage. The surgical time, warm and cold ischemia time, vascular complications, and survival rate on postoperative day seven were compared between the two groups. Results: The modified surgical techniques significantly reduced the surgical duration (35.7 vs. 46.3 min, P<0.01), warm ischemia time (16.3 vs. 28.8 min, P<0.01), and vascular complications (2% vs. 16%, P=0.04). Moreover, the survival rate on postoperative day 7 was higher in the improved surgical techniques group (96% vs. 80%, P=0.03). Conclusions: We described the improvement of surgical techniques for orthotopic single lung transplantation in rats, which could shorten anastomoses time, reduce vascular complications, and improve survival rate.
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OBJECTIVES: Early stage non-small cell lung cancer (NSCLC) patients who undergo complete resection continue to demonstrate high risk of recurrence and death. The advent of the neoadjuvant regimen has brought new hope for these patients. The present study aims to further demonstrate the efficacy of neoadjuvant chemoimmunotherapy. MATERIALS AND METHODS: A real-world observational study was conducted concerning patients who received neoadjuvant pembrolizumab or nivolumab combined with chemotherapy between January 2018 and December 2020 in Shanghai Pulmonary Hospital. The primary endpoint was major pathologic response (MPR), and the secondary endpoints were objective response rate (ORR), pathologic complete response (pCR), disease-free survival (DFS) and toxicity. RESULTS: A total of 76 patients were analyzed and divided into the pembrolizumab (n = 42) and nivolumab groups (n = 34) with a median follow-up time of 12.2 months. Most patients (92%) had stage III disease, with 41 (54%) and 29 (38%) patients initially diagnosed clinical stage IIIA and IIIB, respectively. Fifty (66%), 21 (28%) and 5 (6%) patients received two, three and four cycles of neoadjuvant treatment, separately, achieving an ORR of 75%. None of them needed a reduced initial dose or delay due to intolerable adverse events. Forty-nine (64%) and 28 (37%) patients achieved MPR and pCR, respectively. RNA sequencing showed that MPR associated with increased infiltration of cytotoxic immune cells with tertiary lymphoid structures (TLSs). Histological evaluation highlighted the localization of B cells within TLSs. Forty-two (69%) patients with clinically N2 disease at baseline were downstaged to pathological N0 (39 patients) or N1 (3 patients). One-year-PFS rate of stage III patients was 91%. No difference in baseline characteristics and treatment outcomes was observed between 2 groups. CONCLUSION: The feasibility of neoadjuvant chemoimmunotherapy for resectable NSCLC was further validated, with a high MPR rate and manageable adverse events.
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BACKGROUND: Intravascular leiomyomatosis is a rare benign lesion with malignant potential. The cases are sporadic. Most patients have no clinical symptoms, and the preoperative diagnostic rate is low. Case 1 was misdiagnosed, passively managed during operation, recurred quickly, and underwent a secondary operation. We learned lessons from case 1 and treated the case 2 patient differently. The case 2 patient had a good prognosis. We hope the report will be helpful to other gynecologists. CASE SUMMARY: Case 1: a 49-year-old woman complained of dysmenorrhea. Traditional ultrasound showed adenomyosis and a solid mass 6 * 3 cm in the right appendix. After routine examination, the patient underwent transabdominal total hysterectomy + bilateral salpingectomy + IVL tumor resection, with both ovaries kept. No medication was used after operation. Routine ultrasound was performed every 3 months. The disease recurred, and the patient underwent a secondary surgery 9 months after the first time. So far, 25 months after the secondary surgery, there is no sign of recurrence. Case 2: a 41-year-old woman underwent a routine body examination, where a left adnexal mass 7 cm was found. The patient underwent contrast-enhanced ultrasonography and was diagnosed and prepared well preoperatively. The patient underwent transabdominal total hysterectomy + bilateral salpingectomy + IVL tumor resection. GnRH-a drugs were used after operation for 3 cycle. Now, there is no sign of recurrence after operation for 23 months. CONCLUSION: The incidence rate of IVL is low, and there are no typical clinical symptoms. It is easy to be ignored by gynecologists. Contrast-enhanced ultrasound is helpful to diagnose preoperatively and reduce misdiagnosis. Good preparation, full exploration of the pelvic and abdominal vessels, removal of lesions completely as much as possible, and anti-estrogen therapy after operation can reduce the recurrence of disease.
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Background: The association between a diverse array of environmental risk factors and the risk of endometriosis is contradictory. Objective: To summarize the evidence of associations between environmental risk factors and the risk of endometriosis. Methods: Databases such as PubMed, EMBASE, Web of Science, and ClinicalTrial.gov were systematically searched in June 2020. Meta-analyses of observational studies investigated any environmental exposure (non-genetic) and endometriosis risk. For each article, we estimated the summary effect size, 95% CIs, and the 95% prediction interval (PI). We also estimated the between-study heterogeneity expressed by I 2, evidence for small-study effects, and evidence of excess significance bias. Results: About 12 eligible articles (featuring 143,422 cases and 5,112,967 participants) yielded data on 40 unique environmental risk factors, including life styles (n = 16), reproductive factors (n = 3), early life factors (n = 4), and a range of other risk factors [e.g., phthalate metabolites, endocrine-disrupting chemicals, and body mass index (BMI)]. About 25 of these 40 associations (62.5%) were statistically significant (p < 0.05) under random-effects models. Evidence for an association was indicated for alcohol intake [relative risk (RR): 1.25; 95% CI: 1.11-1.41] and the exposure to endocrine disruptor chemicals (EDCs) (RR: 1.41; 95% CI: 1.23-1.60) while 15 associations presented only weak evidence. Conclusions: Our analyses showed that alcohol intake and exposure to endocrine-disrupting chemicals may be potential risk factors for endometriosis and supported by suggestive epidemiological evidence. However, it was evident that there was substantial heterogeneity and/or bias between the different studies featured in various meta-analyses included in this review; therefore, the outcomes of our analysis should be interpreted cautiously.
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OBJECTIVE@#To investigate the auxiliary diagnostic value of serum adenosine deaminase (ADA) in acute leukemia (AL) at clinical test.@*METHODS@#123 AL patients hospitalized in Zhejiang hospital from November 2018 to March 2020 were enrolled as the observation group, and 98 healthy people in the same period were randomly enrolled as the control group. AL patients were divided into two groups: 77 acute myeloid leukemia (AML) patients for AML group and 46 acute lymphoblastic leukemia (ALL) patients for ALL group. The levels of adenosine deaminase (ADA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) and homocysteine (Hcy) in serum of the patients were detected, and the correlation of ADA with these items was analyzed. Receiver operating characteristic curve (ROC) was used to analyze the clinical diagnostic value of ADA, Yoden index was used to confirm the best cut-off point.@*RESULTS@#The serum ADA level in AL patients was significant higher than that in control group (P < 0.05). The results of Pearson correlation analysis showed that there was a significant positive correlation of ADA with Hcy, ALT, AST, GGT, LDH in AML group (r = 0.47, r = 0.28, r = 0.37, r = 0.22, r = 0.55); and also there was a significant positive correlation of ADA with GGT in ALL group (r = 0.54). In AML group, the maximum area under ROC curve was 0.761 (P = 0.00), 95% confidence interval was 0.682-0.841, sensitivity was 54.50%, specificity was 98.90%, and the best cut-off point was 17.1 U/L. In ALL group, the maximum area under ROC curve was 0.785, 95% confidence interval was 0.694-0.877, sensitivity was 65.90%, specificity was 84.00%, and the best cut-off point was 13.45 U/L.@*CONCLUSION@#The detection of ADA in serum can be used as an auxiliary examination in patients with AL, which can provide a certain value for the diagnosis of the disease.
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Humans , Adenosine Deaminase , L-Lactate Dehydrogenase , Leukemia, Myeloid, Acute/diagnosis , ROC Curve , Retrospective StudiesABSTRACT
Objective:To investigate the effect of pelvic motion in late pregnancy on the outcome of first trimester delivery.Methods:A total of 127 first-borns admitted to the midwifical clinic of Nanjing Maternal and Child Health Hospital from November 1, 2019 to March 10, 2020 were selected as the research objects, and they were divided into the walking group and the pelvic motion group according to the random number table method. In the end, 62 cases were included in the walking group and 65 cases in the pelvic motion group. The walking group did brisk walking in the third trimester. In the pelvic motion group, the motion in the third trimester consisted of the combined pelvic motion involving the two planes of the upright spine and the horizontal spine, and multiple peripelvic joints. The changes of fertility, birth canal and fetus before and after exercise were observed, and the outcomes of childbirth were compared between the two groups.Results:Indicators reflecting productivity: persistence time of "air bike" on the day before delivery was (27.12±7.73) seconds in the pelvic motion group and (20.56±6.60) seconds in the walking group, the difference was statistically significant ( t value was 5.12, P<0.01). The time of contractions after exercise before delivery was (269.38±123.70) seconds in the pelvic motion group and (591.29±201.82) seconds in the walking group, the difference was statistically significant ( t value was 10.89, P<0.01). The indicators reflecting the situation of the maternal birth canal were as follows: "sitting forward flexion level", pelvic motion group was (33.64±5.91) cm, walking group was (29.50±5.28) cm, the difference was statistically significant ( t value was 4.15, P<0.01). The cervical score during regular contractions was 8.01±1.69 in the pelvic motion group and 7.30±1.40 in the walking group, the difference was statistically significant( t value was 2.56, P<0.05). At the beginning of regular contractions, the proportion of fetal "occipital position" was 93.85% (61/65) in the pelvic motion group and 72.58%(45/62) in the walking group, the difference was statistically significant ( χ2 value was 10.41, P<0.01). The "no pain rate after exercise the day before delivery" was 72.31% (47/65) in the pelvic motion group and 29.03% (18/62) in the walking group, the difference was statistically significant ( χ2 value was 25.30, P<0.01). Time of the first labor was (395.84±165.24) min in the pelvic motion group and (574.35±152.23) min in the walking group, the difference was statistically significant ( t value was 6.32, P<0.01). The second stage of labor was (25.98±9.88) min in the pelvic motion group and (33.62±13.94) min in the walking group, the difference was statistically significant ( t value was 3.57, P<0.01). Conclusions:Pelvic motion in middle and late pregnancy can affect labor force, birth canal, fetus and other delivery factors, reduce movement pain and shorten the time of labor.
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Objective To investigate the intestinal mucosal barrier function protective effect of ulinastatin in sepsis rats and its effect on Wnt/β-catenin signaling pathway. Methods One hundred SD rats were randomly divided into control group, sepsis group, ulinastatin group, XAV939+ulinastatin group and lithium chloride( LiCl) +ulinastatin group. The classical cecal ligation was used to duplicate sepsis model, and the jejunal mucosal injury was evaluated. The levels of inflammatory factors interleukin (IL)-6 and tumor necrosis factor(TNF)-α were detected by ELISA, and the expressions of β-catenin and cyclin D1 were detected by Real-time PCR and Western blotting. We also observed the effect of the Wnt signal pathway blockage by XAV939 or Wnt signal pathway activator by LiCl on ulinastatin protection of intestinal mucosa and proteins related to the Wnt signal pathway. Results The levels of IL-6, TNF-α and intestinal mucosal injury in the sepsis group were significantly higher than those in the ulinastatin group. The mRNA and protein expression levels of β- catenin and cyclin D1 in the sepsis group were significantly higher than those in the control group (P<0.05), After ulinastatin treatment, the expression levels of β-catenin and cyclin D1 mRNA and protein were significantly decreased, and the difference was significant (P<0.05). Compared with the ulinastatin group, combined treatment with XAV939 promoted the protective effect of ulinastatin on the intestinal mucosa of rats, and the protein expression of β-catenin and cyclin D1 was reduced (P<0.05). Combined treatment with LiCl weakened the protective effect of ulinastatin on the intestinal mucosa of rats, and the protein expression of β-catenin and cyclin D1 was increased (P<0.05). Conclusion Ulinastatin may inhibit the Wnt signaling pathway by down-regulating the expression of β-catenin, reduce the expression of inflammatory factors IL-6 and TNF-α, thereby promote repairing the intestinal mucosal barrier function damage.
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BACKGROUND: Toll-like receptors (TLRs) play a vital role as a first defense mechanism linking the innate with the adaptive immune system. Prior studies showed that TLR2 participated in immune responses of sarcoidosis. However, the role of TLR2 in the progression of mediastinal lymph nodes associated with sarcoidosis is still unknown. The current study aims to investigate the expression of Toll-like receptors 2 (TLR2) in mediastinal lymph nodes of patients with sarcoidosis. METHODS: Mediastinal lymph nodes biopsy specimens were collected from 10 patients with sarcoidosis and 11 normal controls. The expression of TLR2 in mediastinal lymph nodes was detected by immunohistochemistry. RESULTS: In mediastinal lymph nodes specimens, immunohistochemical examination revealed that expression of TLR2 could be detected in sarcoidosis patients, while it was scarcely detected in the mediastinal lymph nodes of control. The mean optical density of TLR2 in mediastinal lymph nodes of sarcoidosis was significantly higher than controls (124.9±24.3 vs. 92.6±35.2, P=0.026). Among patients with sarcoidosis, correlation analysis showed that the mean optical density of TLR2 in mediastinal lymph nodes positively correlated with the level of 24-hour urinary calcium (R=0.781, P=0.038). CONCLUSIONS: The expression of TLR2 was upregulated in mediastinal lymph nodes of sarcoidosis patients. The expression of TLR2 in mediastinal lymph nodes was associated with the level of 24-hour urinary calcium, suggesting that TLR2 might become another predictor of disease activity.
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BACKGROUND: The traditional definition of late postpartum hemorrhage is a massive uterine hemorrhage from 24 h after delivery to the puerperal period. Here, we report a case of late postpartum hemorrhage that occurred 3 mo after cesarean section and endangered the patient's life. The cause of the case we are reporting was poor incision healing. By reporting this case, we hope to make doctors aware that late postpartum hemorrhage due to poor incision healing may happen as late as 3 mo after cesarean section. CASE SUMMARY: A 31-year-old woman complained of acute, severe vaginal bleeding for 1 h; the patient had a history of cesarean section 3 mo prior. After receiving anti-inflammatory treatment, fluid supplementation, blood transfusion, oxytocin administration, and hemostatic treatment, the vaginal bleeding ceased, and the patient's clinical status improved. Unfortunately, she experienced recurrent massive vaginal bleeding, and uterine contractile agents did not decrease the persistent bleeding. To save the patient's life, she was admitted for emergency laparotomy. At exploratory laparotomy, dehiscence and necrosis of the previous cesarean section scar were noted; the dehiscence penetrated through the entire thickness of the uterine muscle wall and extended to the left uterine artery. Ultimately, we performed a total hysterectomy. CONCLUSION: Late postpartum hemorrhage due to poor incision healing after cesarean section may occur in the 3 mo after cesarean section or even later. Therefore, obstetricians-gynecologists should monitor for this potential complication in all patients post-cesarean section. Such hemorrhages can be severe enough to endanger the patient's life.
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OBJECTIVES: Adenoid cystic carcinoma (ACC) of the trachea and bronchus is rare, representing 1% of all respiratory tract cancers. We presented our experiences in treating tracheal-bronchial ACC and the results of long-term surveillance. METHODS: We conducted a retrospective study of treating tracheo-bronchial ACC. From 2009 to 2014, 42 patients presented to our department. All of them received surgical resection and adjunctive therapy. RESULTS: R0 resections were achieved in 33 patients, whereas 15 patients whose lesions spread outside the tracheo-bronchial lumens. Nine patients had R1 resections followed by radiation and chemotherapy. The 5 year survival rate of R1 resection group showed no difference compared to the R0 resection group, but the 5 year disease-free survival rate showed difference in extra-lumenal invasion (ELI) and non-ELI group (P = 0.0357 < 0.05), although no difference was seen in the overall survival rate in these two groups. CONCLUSIONS: ACC of the trachea and bronchus is a rare and low-to-moderate grade malignant tumor. When the R0 resection is over risky or may cause mortal complication, the R1 resection with adjunctive therapy is acceptable for patients to obtain a promising prognosis, whereas pathological ELI is an adverse prognostic indicator.