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Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
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Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Treatment OutcomeABSTRACT
【Objective】 To evaluate the efficacy and safety of 450 nm semiconductor blue laser combined with triamcinolone acetonide injection in the treatment of bladder neck contracture (BNC). 【Methods】 A 61-year-old male patient with BNC and urethral stricture was treated with 450 nm semiconductor blue laser vaporization combined with triamcinolone acetonide injection. The surgery was performed with a small-caliber laser resectoscope of F22. The follow-up results 3 months after surgery were reported. 【Results】 The operation was successful, the operation time was 30 minutes, and the patient was discharged the next day after operation. Follow-up 3 months after operation showed the maximum urinary flow rate (Qmax) was 22.1 mL/s, the International Prostate Symptom Score (IPSS) was 2, the Quality of Life Scale (QoL) was 0, and no recurrence was observed. 【Conclusion】 It is safe and feasible to use 450 nm semiconductor blue laser combined with triamcinolone acetonide injection to treat bladder neck contracture through a small-caliber laser resectoscope of F22, especially for patients with urethral stricture. The short-term efficacy is satisfactory.
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ObjectiveTo investigate the characteristics of traditional Chinese medicine syndrome and the evolution of pathogenesis in different stages of atherosclerotic thrombotic cerebral infarction （ATCI）. MethodsClinical data of 3088 ATCI patients from 8 hospitals in 6 provinces and cities were collected from the hospital information system during January 1， 2015 to December 31， 2019. After staging and counting clinical symptoms， common factors were extracted using the principal component analysis method in factor analysis. Cluster analysis was then carried out on the basis of the factor analysis. The results of the combination of the evidence element identification， cluster analysis and expert discussion were used to discuss the evidence of the different disease stages of atherosclerotic cerebral infarction. ResultsOf the 3088 ATCI patients included， 2290 cases were in the acute phase and 798 in the non-acute phase. Excluding the main symptoms of ischaemic stroke， such as numbness and weakness of limbs， unfavourable movement， unfavourable speech and dizziness， we identified 84 indicators with a frequency ≥5% of the four diagnostic information variables. Of these， 36 indicators were observed in the acute phase and 35 in the non-acute phase. Factor analysis extracted 14 common factors from each phase. We selected factors with a loading coefficient ＞0.3 for evidence determination. These 14 groups of common factors were used as variables for clustering. After clustering， the acute， non-acute phase were each divided into 5 categories. Based on a combination of clinical practice and expert opinion， the symptoms identified in the acute period were syndrome of deficiency of both qi and yin， syndrome of blockade of wind-phlegm-static blood （36.07%）， syndrome of qi deficiency and blood stasis （20.74%）， syndrome of upward disturbance of wind-fire （15.15%）， syndrome of stirring wind due to yin deficiency （9.43%）， and syndrome of spleen deficiency and liver hyperactivity （3.80%）. In the non-acute phase， the symptoms were qi and yin deficiency with syndrome of qi stagnation and blood stasis （45.49%）， syndrome of deficiency of both qi and yin （20.05%）， syndrome of qi stagnation and blood stasis （16.42%）， spleen-kidney deficiency syndrome （8.52%）， and syndrome of hyperactivity of liver yang （4.89%）. ConclusionThe acute phase of AICI is mainly characterized by blood stasis， fire， internal wind， hyperactivity of yang， qi deficiency and yin deficiency， while the non-acute phase is characterized by yin deficiency， qi deficiency， blood stasis and qi stagnation. The main pathomechanism of ATCI involves deficiency of qi and yin， as well as obstruction of the channels by phlegm and blood stasis， and the fundamental pathomechanism is deficiency of qi and yin.
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Primary angiitis of the central nervous system (PACNS) is a rare inflammatory disease of the central nervous system with unknown etiology affecting the brain and spinal cord. As the incidence of PACNS is low, the clinical manifestations are diverse, the cerebrospinal fluid examination lacks specificity, its diagnosis mainly depends on the "gold standard" pathological biopsy. However, due to the subjectivity of the sampling site, tissue staining and microscopic reading, some patients may be misdiagnosed. In addition, the potentially aggressive course of PACNS may reduce disability and mortality through appropriate immunosuppressive therapy, so the early diagnosis of PACNS is conducive to the prognosis of patients. Imaging examination is convenient, non-invasive, and can provide important information for the diagnosis and differential diagnosis of PACNS from various aspects. Therefore, it is very important to explore the imaging features of the disease. This paper reviews the current research status of imaging examination in PACNS and summarizes the different types of imaging findings in PACNS.
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The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
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Rats , Mice , Animals , Rats, Sprague-Dawley , Angiotensin II/pharmacology , Fibroblasts , Mice, Inbred C57BL , Fibrosis , Collagen/pharmacology , Collagen Type I/metabolism , RNA, Messenger/metabolism , Myocardium/pathologyABSTRACT
AIM: To investigate the clinical efficacy of gonioscopy-assisted transluminal trabeculotomy(GATT)for secondary high intraocular pressure after vitrectomy.METHODS: A retrospective study was conducted on 10 patients(15 eyes)with secondary high intraocular pressure(IOP)after vitrectomy treated with GATT in Department of Ophthalmology, Chengdu First People's Hospital from January 2019 to May 2022. The best-corrected visual acuity(BCVA), IOP, number of IOP-lowering drugs, and complications before operation and at 1d, 1wk, 1, 3 and 6mo after operation were recorded, and the surgical success rate was analyzed.RESULTS:There was no difference in BCVA before and 6mo after operation(Z=0, P=1). The mean IOP decreased from 28.33±9.48mmHg to 17.47±3.78(1d), 18.8±3.29(1wk), 19.13±3.62(1mo), 20.31±3.66(3mo)and 18.03±3.23mmHg(6mo; all P<0.05). The average medication used before surgery was 2(2, 4), and the average medication used 6mo after surgery was 1(0, 2), which was significantly decreased(P<0.001). The total success rate of surgery at 1d, 1wk, 1, 3 and 6mo after surgery was 87%(13 eyes), 93%(14 eyes), 87%(13 eyes), 73%(11 eyes)and 93%(14 eyes)respectively. The main postoperative complications were transient hyphema(10 eyes, 67%)and transient elevated IOP(5 eyes, 33%). No complications seriously affecting the vision occurred.CONCLUSION: GATT is safe and effective in the treatment of secondary high intraocular pressure after vitrectomy.
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We used network pharmacology to predict the mechanism in the treatment of rheumatoid arthritis (RA) via modified Gan Cao Fu Zi Decoction (GCFZ), and validated the results of the analysis and explored the pharmacodynamic effects of GCFZ through animal experiments. Firstly, TCMID, SymMap, HERB, STITCH and GEO databases were utilized to obtain the target genes of GCFZ for the treatment of RA, which yielded a total of 1 250 differentially expressed genes for RA, 534 genes for GCFZ targets and 83 intersecting genes. Then functional enrichment analysis of the intersecting genes was performed through GO and KEGG databases, and the results revealed that GCFZ and its active ingredients mainly functioned through cytokine pathways, where chemokine signaling pathway and tumor necrosis factor (TNF) signaling pathway were enriched with a high number of genes. Cytoscape 3.8.0 software was used to construct the drug-target-disease network and screen key proteins, which included TNF, C-X-C chemokine ligand 8 (CXCL8), C-X-C chemokine ligand 10 (CXCL10), C-C chemokine ligand 5 (CCL5), C-X-C chemokine ligand 2 (CXCL2) and C-X-C chemokine receptor type 4 (CXCR4). The molecular docking technology was used to confirm the binding ability of the main active ingredients of GCFZ to the core proteins. Additionally, the therapeutic effects of GCFZ in low (4 g·kg-1), medium (8 g·kg-1) and high (16 g·kg-1) dose groups were investigated by constructing the collagen-induced arthritis (CIA) rat model. X-ray imaging approach, HE staining and Safranin O-Fast Green staining showed that GCFZ treatment significantly improved bone destruction, synovial hyperplasia and cartilage damage in CIA rats, while immunofluorescence results showed that GCFZ treatment could regulate the expression of TNF, CXCL8 and CCL5. In summary, our results indicate that GCFZ contains a variety of small molecule pharmacodynamic substances, which can exert therapeutic effects via multiple targets and pathways, and obviously reduce the symptoms of arthritis in CIA rats. This animal experiment of our research was approved by the Experimental Animal Management and Ethics Committee of Bengbu Medical College.
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Cannabinoid receptors are one of the most expressed G protein-coupled receptors in the central nervous system, which are potential drug targets for inflammation, pain and drug abuse. Cannabinoid receptors are composed of type 1 receptor (CB1R), type 2 receptor (CB2R) and other receptors, of which CB1R plays a vital role in regulating central memory, cognition, and motor function. Therefore, screening CB1R agonists has potential value in treating nervous system diseases. In this study, the intracellular loop 3 (ICL3) domain of CB1R was replaced with a circular-permutated enhanced green fluorescent protein (cpEGFP). After infecting HEK 293T cells with lentivirus particles, we obtained a stable cell line that was overexpressed human CB1R-cpEGFP after puromycin selection. The interaction between receptor agonists and CB1R led to the change of receptor conformation, resulting in de-protonation of the EGFP, and enhancing the fluorescence intensity. Therefore, active CB1R compounds could be verified by measuring the fluorescence intensity. Using CB1R agonist arachidonyl-2′-chloroethylamide (ACEA) as a positive control to evaluate the reliability of this model, studies have shown that ACEA could induce receptor activation and increase fluorescence intensity, while antagonist rimonabant inhibited receptor activation with unchanged fluorescence intensity. In conclusion, this study successfully constructed a fluorescent probe screening model for CB1R agonists.
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This paper introduces the composition of the Chinese version of the European quality of life five-dimension scale (EQ-5D), including two different level scales, EQ-5D-3L and EQ-5D-5L, and summarizes the status quo of the application of the above scales. This paper sorts out the utility value sets of the EQ-5D-3L and EQ-5D-5L scales currently developed based on the Chinese population, and provide an important reference for Chinese researchers to choose suitable scales for research on health-related quality of life and health economics cost-utility analysis in the future.
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AIM:To explore the effect of intravitreal injection FasL inhibitors on corneal apoptosis, Fas, FasL expression, Treg numbers in blood and lymph nodes and rejection index in rats after corneal transplantation.METHODS:A total of 24 SD rats(24 eyes)who received penetrating keratoplasty were randomly divided into two groups: PBS group received intravitreal injection of PBS(12 rats, 12 eyes)and FasL inhibitor group(12 rats, 12 eyes). Rejection index was recorded every week and blood samples and lymph node were collected at 1, 3 and 5wk after surgery to analyze the proportions of Treg. Corneal tissue was collected for detecting the expression of Fas and FasL and number of apoptosis.RESULTS: The expression of Fas, FasL in FasL inhibitor group decreased significantly compared with the PBS group(all P<0.05); Corneal cell apoptosis significantly decreased in FasL inhibitor group, and it was the lowest at 5wk after surgery; Treg numbers in blood and lymph nodes significantly increased in FasL inhibitor group at 3wk after surgery(all P<0.05); rejection index of corneal transplantation in the FasL inhibitor group was significantly lower than that of PBS group(all P<0.05).CONCLUSION:Intravitreal injection of FasL inhibitors after corneal transplantation could reduce the apoptosis in all layers of cornea, increase the number of Tregs in blood and lymph nodes, and alleviate rejection.
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Hepatitis E is a viral hepatitis that the hepatitis E virus (HEV) causes. In the early 1980s, the hepatitis E virus was first discovered and identified, and it is one of the important pathogens that cause acute viral hepatitis globally. HEV infection is usually self-limiting, but in some groups of populations, such as pregnant women, patients with chronic liver disease, and the elderly, the prognosis is poor and may result in acute or subacute liver failure or even death. In addition, HEV infection can occur in chronically immunocompromised populations. At present, some regions and countries are not paying enough attention to hepatitis E prevention, diagnosis, and treatment, which suggests that we should study the epidemiology of HEV infection.
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Humans , Female , Pregnancy , Aged , Hepatitis E/epidemiology , Hepatitis E virus/genetics , Prognosis , Liver Failure , Pregnancy Complications, InfectiousABSTRACT
A crucial lesson gained through the pandemic preparedness and response to COVID-19 is that all measures for epidemic control must be law-based. The legal system is related not only to public health emergency management per se but also to all aspects of the institutional supporting system throughout the lifecycle. Based on the lifecycle emergency management model, this article analyses the problems of the current legal system and the potential solutions. It is suggested that the lifecycle emergency management model shall be followed to establish a more comprehensive public health legal system and to gather the intelligence and consensus of experts with different expertise, including epidemiologists, sociologists, economists, jurist and others, which will collaboratively promote the science-based legislation in the field of epidemic preparedness and response for the establishment of a comprehensive legal system for public health emergency management and with Chinese characteristics.
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Humans , China , Pandemics/prevention & control , Public Health , Emergencies , Disaster PlanningABSTRACT
Parkinson's disease (PD) is a degenerative disease of the central nervous system due to the loss or death of dopaminergic neurons in the substantia nigra. Clinically, levodopa is the most effective and commonly used drug for PD treatment. However, long-term levodopa therapy is prone to motor complications and other side effects caused by excessive peripheral dopamine production, which has become an urgent problem to be solved in PD treatment. Dopamine receptor (DR) agonists are similar to dopamine. They can directly stimulate postsynaptic dopamine receptors, produce the same effect as dopamine, delay the application of levodopa as much as possible, and reduce complications caused by long-term use of levodopa. Therefore, screening effective dopamine receptor agonists has become a key issue in the study and treatment of PD. In order to establish a rapid, stable and reliable method for dopamine receptor agonist screening, this study used the human dopamine receptor 2 (DRD2) gene fused with a circular permuted EGFP (cpEGFP) to construct a recombinant gene, packaged with lentiviral vector, and the vector replaced the parted inner transmembrane domain of the third intracellular loop (ICL3) of genetically-encoded GPCR-activation based (GRAB) sensors. The fluorescence of GPCR-fused cpEGFP is regulated by conformational changes mediated by the interaction of dopamine receptor agonists with GPCRs without altering GPCR activity. The HEK293T cells were infected with viral vector, screened by puromycin to select highly expressed cells. Dopamine receptor agonists (including dopamine, bromocriptine mesylate, cabergoline, pramipexole) were used as positive drugs to explore the best screening and detection conditions, establishing a stable model to evaluate the dopamine receptor agonist. The results showed that the optimal filter for the dopamine receptor agonist in this study was the cell seeding count of 7×104, and the effective concentration of the positive drug was 1-100 µmol·L-1. In addition, pretreated with 10 µmol·L-1 dopamine receptor antagonists (including chlorprothixol hydrochloride, domperidone, and sulpiride), the positive fluorescence signal of overexpressed DRD2-cpEGFP HEK293T cells could not be detected when exposed to 10 µmol·L-1 dopamine receptor agonists, which proved that dopamine receptor antagonists could block the activity of dopamine receptor agonists, so they cannot activate dopamine receptor allosteric, indicating that the model has good specificity and can also be used for the screening and detection of new dopamine receptor antagonists. In summary, the study constructs a stable dopamine sensor detection system, which can effectively screen potential dopamine receptor agonists. The operation procedures are simple and rapid. And it can be used for a large-scale screening providing a fundamental methodology for drug development and PD treatment targeted on DRD2.
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ObjectiveThe objective is to investigate the possibility of isocenter dual-guided resetting of surface guided radiation therapy （SGRT） combined with image guided radiation therapy （IGRT） in postoperative radiotherapy for breast cancer. To assess the setup error accuracy between the new resetting mode and the traditional resetting mode. MethodsRetrospective analysis was performed on breast cancer patients who underwent ELEKTA infinity accelerator radiotherapy in sun yat-sen university cancer center from July 13， 2021 to October 15， 2022. According to different reset methods， the patients were divided into a simulation group （41 cases） and a dual-guided group （40 cases）. The simulation group was reset using a simulator， CBCT scans were performed and setup errors were recorded during the first treatment； The dual-guided group was guided by AlignRT and combined with CBCT for isocenter dual-guided resetting， and the setup error obtained by CBCT registration was recorded. The global setup errors of chest region of interest （CROI） ， the local residual errors of supraclavicular region of interest （SROI） and the resetting time of the two reset methods were calculated and compared respectively. The advantages of the CBCT error distribution in the dual-guided resetting of SGRT combined with IGRT were analyzed. ResultsThe median of the global setup errors （X/cm， Y/cm， Z/cm， Rx°， Ry°， Rz°） of the simulation group and the median of the dual-guided group in the CROI were statistically significant （P<0.05） except the Rz and Ry directions. The local residual errors of the two groups of the SROI were calculated. The median of the errors of X/cm， Y/cm， Z/cm， Rx°， Ry°， Rz° were statistically significant （P<0.05） except the X and Y axis. The resetting time of the simulation group was significantly longer than that of the dual-guided group （238.64±28.56） s， t=-24.555， P=0.000， and the difference was statistically significant （P<0.05）. The CBCT error distribution of the dual-guide group was analyzed， and it was found that the absolute values of translation errors of X， Y and Z axis were all within 0.4 cm， while the proportions of ≤ 0.3 cm were 95%， 93% and 93%， respectively. The proportions of rotation errors of Rx， Ry and Rz ≤ 1.5 ° were 90%， 93% and 90%， respectively. ConclusionIn postoperative radiotherapy of breast cancer， SGRT combined with IGRT for isocenter dual-guided resetting can effectively correct the rotational setup errors and residual errors， and improve the accuracy of radiotherapy with less resetting time and high feasibility， which compared with the traditional simulator resetting mode. This precise， unmarked resetting method can be widely used in clinical practice.
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The chemical components of Huanglian Decoction were identified by ultra-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS) technology. The gradient elution was conducted in Agilent ZORBAX Extend-C_(18) column(2.1 mm×100 mm, 1.8 μm) with the mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B) at a flow rate of 0.3 mL·min~(-1) and the column temperature of 35 ℃. The MS adopted the positive and negative ion mode of electrospray ionization(ESI), and the MS data were collected under the scanning range of m/z 100-1 500. Through high-resolution MS data analysis, combined with literature comparison and confirmation of reference substances, this paper identified 134 chemical components in Huanglian Decoction, including 12 alkaloids, 23 flavonoids, 22 terpenes and saponins, 12 phenols, 7 coumarins, 12 amino acids, 23 organic acids, and 23 other compounds, and the medicinal sources of the compounds were ascribed. Based on the previous studies, 7 components were selected as the index components. Combined with the network pharmacology research and analysis me-thods, the protein and protein interaction(PPI) network information of the intersection targets was obtained through the STRING 11.0 database, and 20 core targets of efficacy were screened out. In this study, UPLC-Q-TOF-MS/MS technology was successfully used to comprehensively analyze and identify the chemical components of Huanglian Decoction, and the core targets of its efficacy were discussed in combination with network pharmacology, which laid the foundation for clarifying the material basis and quality control of Huanglian Decoction.
Subject(s)
Tandem Mass Spectrometry , Network Pharmacology , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , TechnologyABSTRACT
Objective: To investigate the safety and effect of laparoscopy for the treatment of biliary stricture after the biliary dilatation operation. Methods: The clinical data of 78 patients,including 27 males and 51 females aged (48.6±14.2)years(range:17 to 76 years),who presented biliary stricture after biliary dilatation operation from January 2017 to June 2021 in the Department of Minimally Invasive Hepatobiliary Surgery,Hunan Provincial People's Hospital,were retrospectively collected,with 38 cases in the laparoscopy group and 40 cases in the laparotomy group. Of the 78 patients,there were 67 cases of cholangiojejunostomy stricture and 11 cases of stricture of the high intrahepatic bile duct. Statistical methods such as t-test and χ2 test were carried out to compare perioperative clinical data and follow-up information between the two groups. Results: Less intraoperative blood loss((102.6±76.4)ml vs. (162.5±105.9) ml, t=-2.874,P=0.005),shorter postoperative stay length of stay((10.5±3.7)days vs. (14.5±6.4)days, t=-3.379,P=0.001) and shorter waiting time for postoperative anal exhaust((2.0±0.6)days vs. (2.5±0.9)days, t=-2.827,P=0.006) were found in the laparoscopy group than that in the laparotomy group,with statistically significant differences. While there was no statistically difference in the operative time((252.8±54.7)minutes vs. (257.4±68.6)minutes,t=-0.331,P=0.742). Postoperative review and follow-up did not show statistically significant differences between the two groups in the residual stone rate(5.3%(2/38) vs. 5.0%(2/40)) and the incidence of recurrent biliary stricture(5.3%(2/38) vs. 7.5%(3/40))(both P>0.05). Conclusion: Laparoscopy may be safe and effective in the treatment of biliary stricture after the biliary dilatation operation,with less trauma,faster recovery compared to laparotomy.
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Objectives: To construct a nomogram for prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis based on inflammation-related markers,and to conduct its clinical verification. Methods: Clinical and pathological data of 858 ICC patients who underwent radical resection were retrospectively collected at 10 domestic tertiary hospitals in China from January 2010 to December 2018. Among the 508 patients who underwent lymph node dissection,207 cases had complete variable clinical data for constructing the nomogram,including 84 males,123 females,109 patients≥60 years old,98 patients<60 years old and 69 patients were pathologically diagnosed with positive lymph nodes after surgery. Receiver operating characteristic curve was drawn to calculate the accuracy of preoperative imaging examinations to determine lymph node status,and the difference in overall survival time was compared by Log-rank test. Partial regression squares and statistically significant preoperative variables were screened by backward stepwise regression analysis. R software was applied to construct a nomogram,clinical decision curve and clinical influence curve,and Bootstrap method was used for internal verification. Moreover,retrospectively collecting clinical information of 107 ICC patients with intraoperative lymph node dissection admitted to 9 tertiary hospitals in China from January 2019 to June 2021 was for external verification to verify the accuracy of the nomogram. 80 patients with complete clinical data but without lymph node dissection were divided into lymph node metastasis high-risk group and low-risk group according to the score of the nomogram among the 858 patients. Log-rank test was used to compare the overall survival of patients with or without lymph node metastasis diagnosed by pathology. Results: The area under the curve of preoperative imaging examinations for lymph node status assessment of 440 patients was 0.615,with a false negative rate of 62.8% (113/180) and a false positive rate of 14.2% (37/260). The median survival time of 207 patients used to construct a nomogram with positive or negative postoperative pathological lymph node metastases was 18.5 months and 27.1 months,respectively (P<0.05). Five variables related to lymph node metastasis were screened out by backward stepwise regression analysis,which were combined calculi,neutrophil/lymphocyte ratio,albumin,liver capsule invasion and systemic immune inflammation index,according to which a nomogram was constructed with concordance index(C-index) of 0.737 (95%CI: 0.667 to 0.806). The C-index of external verification was 0.674 (95%CI:0.569 to 0.779). The calibration prediction curve was in good agreement with the reference curve. The results of the clinical decision curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.32,the maximum net benefit could be obtained by 0.11,and the cost/benefit ratio was 1∶2. The results of clinical influence curve showed that when the risk threshold of high lymph node metastasis in the nomogram was set to about 0.6,the probability of correctly predicting lymph node metastasis could reach more than 90%. There was no significant difference in overall survival time between patients with high/low risk of lymph node metastasis assessed by the nomogram and those with pathologically confirmed lymph node metastasis or without lymph node metastasis (Log-rank test:P=0.082 and 0.510,respectively). Conclusion: The prediction accuracy of preoperative nomogram for ICC lymph node metastasis based on inflammation-related markers is satisfactory,which can be used as a supplementary method for preoperative diagnosis of lymph node metastasis and is helpful for clinicians to make personalized decision of lymph node dissection for patients with ICC.
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Objective: To establish a predictive model for survival benefit of patients with intrahepatic cholangiocarcinoma (ICC) who received adjuvant chemotherapy after radical resection. Methods: The clinical and pathological data of 249 patients with ICC who underwent radical resection and adjuvant chemotherapy at 8 hospitals in China from January 2010 to December 2018 were retrospectively collected. There were 121 males and 128 females,with 88 cases>60 years old and 161 cases≤60 years old. Feature selection was performed by univariate and multivariate Cox regression analysis. Overall survival time and survival status were used as outcome indicators,then target clinical features were selected. Patients were stratified into high-risk group and low-risk group,survival differences between the two groups were analyzed. Using the selected clinical features, the traditional CoxPH model and deep learning DeepSurv survival prediction model were constructed, and the performance of the models were evaluated according to concordance index(C-index). Results: Portal vein invasion, carcinoembryonic antigen>5 μg/L,abnormal lymphocyte count, low grade tumor pathological differentiation and positive lymph nodes>0 were independent adverse prognostic factors for overall survival in 249 patients with adjuvant chemotherapy after radical resection (all P<0.05). The survival benefit of adjuvant chemotherapy in the high-risk group was significantly lower than that in the low-risk group (P<0.05). Using the above five features, the traditional CoxPH model and the deep learning DeepSurv survival prediction model were constructed. The C-index values of the training set were 0.687 and 0.770, and the C-index values of the test set were 0.606 and 0.763,respectively. Conclusion: Compared with the traditional Cox model, the DeepSurv model can more accurately predict the survival probability of patients with ICC undergoing adjuvant chemotherapy at a certain time point, and more accurately judge the survival benefit of adjuvant chemotherapy.
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OBJECTIVE@#To explore the effects of morphological changes such as vertebral wedge deformation and disc degeneration (collapse) on adult thoracolumbar/lumbar degenerative kyphosis(TL/LDK) deformity.@*METHODS@#A retrospective analysis of 32 patients with spinal TL/LDK deformity admitted from August 2015 to December 2020, including 8 males and 24 females, aged 48 to 75(60.3±12.4) years old. On the long-cassette standing upright lateral radiographs, the coronal Cobb angle, sagittal thoracic lumbar/lumbar kyphosis angle(KA) of spine were measured, and the height and wedge parameters of apex vertebral(AV) and two vertebrae(AV-1, AV-2, AV+1, AV+2) above and below AV and the intervertebrae and the intervertebral disc(AV-1D, AV-2D, AV+1D, AV+2D) were evaluated, involving anterior vertebral body height(AVH), posterior vertebral body height(PVH), vertebral wedge angle(VWA), ratio of vertebral wedging(RVW), anterior disc height(ADH), posterior disc height(PDH), disc wedge angle(DWA), ratio of disc wedging(RDW), and DWA/KA.@*RESULTS@#The average angle of kyphosis was (44.2±19.1)°. A significant decrease in anterior height of vertebral was observed compared to the posterior height of vertebral(P<0.005). There was no significant difference in anterior and posterior height of discs. The vertebral wedging ratio/contribution ratio:AV-2(14.98±10.95)%/(14.21±8.08)%, AV-1(21.08±12.39)%/(18.09±7.38)%, AV(26.94±11.94)%/(25.52±8.64)%, AV+1(24.19±8.42)%/(20.82±8.69)%, AV+2(20.56±7.80)%/(15.60±9.71)%, total contribution(94.23±22.25)%, the disc wedging ratio/contribution ratio:AV-2D(2.88±2.57)%/(5.27±4.11)%, AV-1D(1.98±1.41)%/(2.29±2.16)%, AV+1D(-5.54±3.75)%/(-0.57±0.46)%, AV+2D(-8.27±4.62)%/(-1.22±1.11)%, total contribution (5.77±4.79)%. And the contribution rate of AV was significantly higher than that of adjacent vertebral(P<0.05).@*CONCLUSION@#The vertebral body and intervertebral disc shape both have influence on thoracolumbar kyphosis. However, the contribution of vertebral morphometry to the angle of TL/LDK deformity is relatively more important than the disc. The contribution of the wedge change of the AV to the TL/LDK deformity is particularly significant.
Subject(s)
Male , Adult , Female , Humans , Middle Aged , Aged , Retrospective Studies , Thoracic Vertebrae/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Kyphosis , Scoliosis , Intervertebral DiscABSTRACT
@#Objective To systematically summarize the effect of flipped classroom (FC) in physiotherapy teaching.Methods The following electronic bibliographic databases were searched from inception to June, 2021: CENTRAL, Medline, EMBASE, CINAHL plus, Academic Search Premier, Teacher Reference Center, ERIC, and Education Research. Original researches about FC for physiotherapy teaching were searched. The researches were screened, selected, extracted and assessed independently by two researchers, and, systematically reviewed.Results and Conclusion A total of 1 307 literatures were retrieved, and seven studies involving at least 770 student participants were finally included, which published mainly from 2013 to 2019. The subjects were students majored in physiotherapy, and the primary outcome index was exam results. FC teaching model generally can improve students' written test scores and enhance their high-level thinking ability. Students and teachers generally hold a positive attitude towards the FC teaching model.