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There is growing evidence that the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased risks of psychiatric sequelae. Depression, anxiety, cognitive impairments, sleep disturbance, and fatigue during and after the acute phase of COVID-19 are prevalent, long-lasting, and exerting negative consequences on well-being and imposing a huge burden on healthcare systems and society. This current review presented timely updates of clinical research findings, particularly focusing on the pathogenetic mechanisms underlying the neuropsychiatric sequelae, and identified potential key targets for developing effective treatment strategies for long COVID. In addition, we introduced the Formosa Long COVID Multicenter Study (FOCuS), which aims to apply the inflammation theory to the pathogenesis and the psychosocial and nutrition treatments of post-COVID depression and anxiety.
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Ankle fracture is caused by direct or indirect violence to the integrity and continuity of the distal tibia and/or fibula, often associated with ligament and other soft tissue injuries. However, ankle fracture can be easily overlooked during diagnosis and treatment due to hidden injuries or lack of experience, often resulting in poor prognosis. The existing classifications are sometimes difficult to provide guidances for clinical decision making, so the classification of ankle fracture based on stability criteria comes into being. Improper management of unstable ankle fracture can lead to serious complications such as loss of function and traumatic arthritis, requiring individualized treatment based on the specific injury. The authors review the concept, anatomy and imageological evaluation of ankle fracture stability as well as its treatment based on stability classification, so as to provide new ideas for the stability evaluation and treatment of ankle fracture.
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Objective:To investigate the efficacy of posterior ankle arthroscopic microfracture with platelet-rich plasma (PRP) injection for the treatment of posterior osteochondral lesions of the talus (OLT).Methods:A retrospective case series study was conducted on clinical data of 13 patients with posterior OLT admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University from September 2019 to October 2020. There were 10 males and 3 females, aged 10-65 years [(38.2±15.9)years]. According to Hepple′s classification, four patients were with type II, three with type IV, and six with type V. According to Elias′ grid scheme, nine patients were in zone 7 and four patients in zone 9. The disease duration was 13-51 months [(26.2±11.4)months]. All patients underwent posterior ankle arthroscopic microfracture with PRP injection. The operation time was recorded. The visual analogue scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and ankle range of motion (ROM) were compared before operation and at 3 months and 1 year after operation. The magnetic resonance observation of cartilage repair tissue (MOCART) score was used to evaluate the repair of cartilage injury at 1 year after operation. Complications were recorded.Results:All patients were followed up for 12-25 months [(15.7±3.7)months]. The operation time ranged from 50 to 90 minutes [(63.8±13.3)minutes]. The VAS improved from 3.0(3.0, 4.0)points before operation to 1.0(0, 2.0)points at 3 months after operation and 1.0(0,1.5)points at 1 year after operation; the AOFAS ankle-hindfoot score was improved from (66.1±11.8)points before operation to (84.8±9.5)points at 3 months after operation and (92.9±8.6)points at 1 year after operation; the ankle ROM was improved from (48.5±7.5)° before operation to (61.9±10.3)° at 3 months after operation and (65.4±11.8)° at 1 year after operation (all P<0.05). There was no significant difference in VAS at 3 months and 1 year after operation ( P>0.05). There were significant differences in AOFAS ankle-hindfoot score and ankle ROM at 3 months and 1 year after operation (all P<0.05). According to AOFAS ankle-hindfoot score, the results were excellent in 11 patients, good in one, and fair in one, with the excellent and good rate of 92%. The MOCART score was 40-85 points [(70.4±14.2)points] at 1 year after operation. There was no postoperative necrosis, infection or neurovascular injury. Two patients had slight transient pain during rehabilitation training and were improved after non-surgical treatment. Conclusion:For posterior OLT, posterior ankle arthroscopic microfracture with PRP injection can effectively alleviate pain, improve ankle function and repair cartilage damage, with satisfactory short-term efficacy.
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Objective:To evaluate the short-term outcome of arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy for the treatment of chronic lateral ankle instability combined with subtle cavus foot.Methods:A retrospective cohort study was conducted to analyze the clinical data of 12 patients suffering chronic lateral ankle instability combined with subtle cavus foot admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University from November 2016 to November 2020, including 5 males and 7 females, aged 16-62 years [(40.3±15.1)years]. All patients were treated with arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy. The calcaneal pitch angle, Meary′s angle and medial cuneiform height on the foot weight-bearing lateral view plus calcaneus valgus angle on the hindfoot long axial view were compared to evaluate the improvement of bony structure and foot alignment preoperatively and at 3 months and 1 year postoperatively. At the same time, American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) were used to evaluate the improvement of ankle function and pain. Postoperative complications were also observed and recorded.Results:All patients were followed up for 1-3 years [(1.6±0.6)years]. The calcaneal pitch angle was decreased from (24.6±5.3)° preoperatively to (22.5±4.9)° at postoperative 3 months and (22.3±5.0)° at postoperative 1 year; the Meary′s angle was decreased from 6.6°(5.2°,7.6°) preoperatively to 2.5°(0.5°,3.8°) at postoperative 3 months and 2.1°(0.5°,3.2°) at postoperative 1 year; the medial cuneiform height was decreased from (24.3±5.3)mm preoperatively to (22.3±4.8)mm at postoperative 3 months and (22.3±4.6)mm at postoperative 1 year; the calcaneus valgus angle was increased from -7.1°(-10.3°,-5.9°) preoperatively to 2.3°(-2.5°,4.5°) at postoperative 3 months and 2.4°(-1.6°,3.8°) at postoperative 1 year (all P<0.01). However, there were no significant differences in the calcaneal pitch angle, Meary′s angle, medial cuneiform height, and calcaneus valgus angle at postoperative 3 months and 1 year (all P>0.05). AOFAS ankle-hindfoot score was increased from (66.8±8.7)points preoperatively to (81.0±5.9)points at postoperative 3 months and (88.6±3.6)points at postoperative 1 year (all P<0.01). According to AOFAS ankle-hindfoot score, the results were excellent in four patients and good in eight patients at postoperative 1 year, with the excellent and good rate of 100%. VAS was decreased from 2.5(2.0,4.0)points preoperatively to 2.0(1.3,2.8)points at postoperative 3 months and 1.0(0,2.0)points at postoperative 1 year (all P<0.01). There were significant differences in the AOFAS ankle-hindfoot score and VAS at postoperative 3 months and 1 year (all P<0.05). Wound malunion was seen in one patient, and healed with a dress changing. All patients had no complications such as vascular or nerve injury. There was no recurrence of malformation or joint instability during 1-year follow-up. Conclusion:For chronic lateral ankle instability combined with subtle cavus foot, arthroscopic modified Brostr?m procedure plus minimally invasive calcaneal osteotomy can stabilize ankle joint, correct hindfoot alignment, improve function and relieve pain.
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Objective:To investigate the clinical effectiveness of da Vinci robotics in thyroid surgery.Methods:304 cases of robotic thyroid surgery performed by the same experienced surgeon at the Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University during the period from Apr. 3, 2020 to Nov. 5, 2021 were prospectively included, and the operation time, operation type, postoperative drainage, postoperative hospital stay, total number of lymph node dissection and number of positive lymph nodes, operation complications, and postoperative pain level of all patients were counted. The learning curve was plotted by applying the moving average method, divided into the initial stage and the mature stage, and the differences in surgical outcomes and surgical complications between the two stages were compared. SPSS 23.0 was applied for statistical analysis, and t-test and Mann-Whitney U test were used for comparison of measurement data, and χ2 test was used for comparison of count data. Result:All surgeries were completed successfully without conversion to open cases, including 29 males and 275 females, with a mean age of (33.8±8.9) years and a range of 27-41 years. The mean body mass index (BMI) was (22.9±3.6) kg/m 2 and a range of 20.5-25.4 kg/m 2. The median operative time was 140 min, the median postoperative drainage was 52.5 ml, and the median postoperative hospital stay was 3 days. The mean number of lymph nodes cleared was 4.4±3.5, and the mean number of positive lymph nodes was 0.9±1.7. The incidence of postoperative transient laryngeal nerve (RLN) injury was 3.3%, and the incidence of transient hypoparathyroidism was 0.7%. A significant decrease in operative time occurred after the 26th case and subsequently stabilized. Compared with the initial stage of the learning curve, the mature stage had a shorter operative time (146.0±36.5 vs 198.7±56.7 min, P<0.001) , a lower incidence of temporary RLN injury (2.5% vs 11.5%, P<0.05) , and a lower percentage of benign tumor surgery (12.2% vs 26.9%, P<0.05) . Conclusion:The application of robotic technology in thyroid surgery is safe and reliable, and its successful implementation should follow a corresponding learning curve, from easy to difficult, with different surgical approaches selected according to the patient’s condition, wishes, and the operator’s technical level.
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Ankle osteoarthritis is a degenerative change caused by the destruction of articular cartilage, and it is not difficult to obtain a preliminary clinical diagnosis. However, imaging evaluation is always needed to evaluate the alignment of lower limbs, potential deformity and prognosis. Therefore, it is particularly important to select the right imaging examination to determine the range of joint inflammation, the degree of deformity and the stage of the disease. This paper discusses the imaging examination and clinical correlation of ankle osteoarthritis at home and abroad, in order to summarize the latest clinical experience for the diagnosis and evaluation of ankle osteoarthritis.
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OBJECTIVE@#To investigate the surgical skills and clinical curative results of arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome.@*METHODS@#From February 2019 to August 2020, 13 patients with ankle instability combined with anteromedial impingement were retrospectively analyzed. There were 10 males and 3 females with age of (40.0±15.1) years old. The course of disease was(44.1±33.2) months. All patients had history of ankle sprain. MRI showed the injury of anterior talofibular ligament. All patients had anteromedial pain and pressing pain when ankle dorsiflexion. All patients were treated with ankle debridement and Brostr?m-Gould surgery under ankle arthroscopic. Postoperative results were evaluated by VAS(visual analogue scale) and AOFAS-AH(American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale, AOFAS-AH).@*RESULTS@#All 13 patients completed the surgery successfully with an operative time of 60 to 90 minutes. All the surgical incisions healed by first intention, and no complications such as incision infection, skin necrosis and neurovascular injury. Follow-up time was (18.1±4.7) months. At the latest follow-up, the VAS score was 1.2±1.1, which was significantly lower than the preoperative score 4.8±1.5 (P<0.05);the AOFAS-AH score 94.2±5.1 was significantly higher than the preoperative score 65.5±11.5 (P<0.05). The AOFAS-AH score at the final follow-up ranged from 84 to 100. All patients walked with normal gait without ankle instability or impingement recurrence.@*CONCLUSION@#Ankle anteromedial impingement syndrome combined with ankle instability is easy to be ignored clinically. Such kind of anteromedial impingement syndrome is mostly related to osteophyte at dorsal medial talar neck. Arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome has satisfactory curative effect with safety and minimal injury.
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Adult , Ankle , Arthroscopy/methods , Female , Humans , Joint Instability/surgery , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
The present study explored the drying effect of new spiral vibration drying technology on Chinese medicinal pills with Liuwei Dihuang Pills, Zhuanggu Guanjie Pills, and Muxiang Shunqi Pills as model drugs. With the drying uniformity, drying time, energy consumption, pill split, dissolution time, and change of index components as evaluation indicators, the drying effect of spiral vibration drying technology on model drugs was evaluated and compared with traditional drying methods, such as hot air drying and vacuum drying in the oven. The dynamic changes of moisture in Liuwei Dihuang Pills with different drying time were investigated. Compared with the traditional drying methods in the oven(hot air drying and vacuum drying) at 80 ℃, the spiral vibration drying only took 80 min, shortened by 80%, with 10%-13% energy consumed. The results showed that the moisture of Liuwei Dihuang Pills was negatively related to the drying time. By virtue of multi-layer countercurrent drying and super resonant fluidization techniques, the new spiral vibration drying technology can significantly improve the drying quality of Chinese medicinal pills, improve the drying efficiency, and enhance the manufacturing capacity of Chinese medicinal pills. This study is expected to provide references for the innovation and development of new drying technology of Chinese medicinal pills.
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China , Desiccation , Physical Therapy Modalities , Technology , VibrationABSTRACT
Previously, Carthami Flos and Lepidii Semen(CF-LS) drug pair has been proved effective in inhibiting myocardial fibrosis(MF) by blunting the activity of cardiac fibroblasts. The present study explored the underlying mechanism of CF-LS in inhibiting MF by improving the cardiac microenvironment based on network pharmacology combined with experimental verification. Active compounds and potential targets of CF-LS were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the potential targets of MF were obtained from GeneCards, Online Mendelian Inheritance in Man(OMIM), and Pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGKB). The "active component-target-MF" network was constructed and analyzed by Cytoscape 3.8.1. The protein-protein interaction(PPI) network was constructed by STRING. The Gene Ontology(GO) biological process enrichment analysis was performed by CluoGO plug-in. Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analysis was performed by R 4.0.2 and Funrich. Subsequently, the inhibitory effect of CF-LS on MF was investigated based on angiotensin Ⅱ(Ang Ⅱ)-induced MF rats. RT-PCR and ELISA were used to verify the effect of CF-LS on the targets of signaling pathways related to vascular endothelial cells predicted by the network pharmacology. Thirty-one active components and 204 potential targets of CF-LS, 4 671 MF-related targets, and 174 common targets were obtained. The network analysis showed that the key targets of CF-LS against MF included RAC-alpha serine/threonine-protein kinase(AKT1), transcription factor AP-1(JUN), mitogen-activated protein kinase 1(MAPK1), cellular tumor antigen p53(TP53), transcription factor p65(RELA), and mitogen-activated protein kinase 8(MAPK8). Biological processes mainly involved regulation of blood vessel diameter, regulation of blood vessel endothelial cell migration, cell death in response to oxidative stress, etc. Advanced glycation end products(AGE)-receptor for advanced glycation end products(RAGE) signaling pathway, phosphoinositide 3-kinase(PI3 K)-serine/threonine protein kinase(AKT) signaling pathway, hypoxia-inducible factor-1(HIF-1) signaling pathway, integrin signaling pathway, transforming growth factor-β(TGF-β) signaling pathway, etc. were involved in signaling pathway enrichment. Literature retrieval confirmed that some of these signaling pathways were closely related to vascular endothelial cells, including AGE-RAGE, PI3 K-AKT, HIF-1α, p53, the transcription factor activator protein-1(AP-1), integrin, p38 MAPK, and TGF-β. Animal experiments showed that CF-LS inhibited MF induced by Ang Ⅱ in rats by suppressing the expression of RAGE, HIF-1α, integrin β6, and TGF-β1. The inhibitory effect of CF-LS on MF has the characteristics of multiple components, multiple targets, and multiple pathways. CF-LS can inhibit MF by regulating the activity of vascular endothelial cells in the cardiac microenvironment.
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Animal Experimentation , Animals , Drugs, Chinese Herbal/pharmacology , Endothelial Cells , Fibrosis , Medicine, Chinese Traditional , Molecular Docking Simulation , Network Pharmacology , Phosphatidylinositol 3-Kinases , Rats , SemenABSTRACT
Background Polycyclic aromatic hydrocarbons (PAHs) are one of the most widely distributed and harmful organic pollutants in the atmosphere. Objective To investigate the distribution characteristics and composition sources of PAHs in the atmosphere of two districts of Lanzhou from 2019 to 2020 and evaluate the health risks of PAHs via inhalation to different populations. Methods The PAHs concentrations in two urban areas (Chengguan District and Xigu District) of Lanzhou City from January 2019 to December 2020 were regularly monitored. Mann-Whitney U test was used to compare differences in target pollutant concentrations between the two areas. Diagnostic ratio method and principal component analysis were adopted for source identification. Incremental lifetime cancer risk (ILCR) model was applied to evaluate the health risks of PAHs. Results The M (P25, P75) PAHs concentrations in Chengguan District and Xigu District were 24.04 (14.59, 41.81) ng·m−3 and 25.97 (18.59, 42.56) ng·m−3, respectively, with no significant difference (Z=−0.970, P>0.05). As to seasonal distribution, most PAHs monomer concentrations in Chengguan District were higher than those in Xigu District in summer, and the concentrations of benzo[a]anthracene and benzo[g,h,i]perylene in Chengguan District were also higher than those in Xigu District in spring and autumn (P<0.05), but there were no significant differences in PAHs monomer concentrations between the two urban areas in winter (P>0.05). Ring number of PAHs exhibited seasonal fluctuations. In winter and spring, the highest proportions in Chengguan District and Xigu District were both 4-ring PAHs (37.32%-41.73%, 35.20%-39.66%), and in summer and autumn, the highest proportions were both 2- and 3-ring PAHs (39.38%-49.54%, 47.17%-51.23%). The results of diagnostic ratio method revealed mixed atmospheric PAHs sources in the two urban areas, including fossil fuel, coal, and biomass combustion. The results of principal component analysis showed that the cumulative contribution rate of the four principal component factors reached 79.54%. Principal component 1 included phenanthrene, anthracene, fluoranthene, pyrene, chrysene, benzo[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]pyrene; principal component 2 included acenaphthene and dibenzo[a,h]anthracene; principal component 3 was fluorene; principal component 4 was naphthalene. The results of health risk assessment showed that the ILCR values of adult males, adult females, and children in Chengguan District were 2.30×10−6, 2.16×10−6, and 1.73×10−6, respectively; and those in Xigu District were 1.58×10−6, 1.48×10−6, and 1.19×10−6, respectively; all were greater than 10−6. Conclusion PAHs pollution exists in the atmosphere of the two urban areas of Lanzhou City, mainly comes from mixed sources of fossil fuels, coal, and biomass burning, and may pose potential carcinogenic risks to the population.
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Background Air pollutants PM2.5 and its adsorbed metal elements are important factors affecting public health. Objective To explore the distribution characteristics and sources of metal elements in atmospheric PM2.5 in Lanzhou from 2019 to 2020, and to assess the health risks of metal elements to different groups of residents through inhalation. Methods From January 2019 to December 2020 in two districts of Lanzhou City (Chengguan District and Xigu District), regular PM2.5 and metal elements [antimony (Sb), aluminum (Al), arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), lead (Pb), manganese (Mn), nickel (Ni), selenium (Se), and thallium (Tl)] were regularly monitored, and their concentrations were described by the median (M) and 25th and 75th percentiles (P25, P75) as not following a normal distribution (because the detection rates of the five elements Be, Cr, Hg, Ni, and Se were less than 70%, the five elements were not included in subsequent analysis), and then compared with the secondary concentration limits in the Ambient Air Quality Standards (GB 3095-2012). The differences between the medians of the two groups were compared by the Mann-Whitney U rank sum test, and the differences among the medians of multiple groups were compared by the Kruskal-Wallis H rank sum test; the enrichment factor (EF) method and principal component analysis were used to evaluate the pollution degree of the metals and their sources; the health risks of five non-carcinogenic metals (Sb, Al, Pb, Mn, and Tl) and two carcinogenic metals (As and Cd) in PM2.5 were evaluated by hazard index (HI) and hazard quotient (HQ) using the incremental lifetime cancer risk (LCR) model and the non-carcinogenic risk assessment model, respectively. Results The PM2.5 concentrations [M (P25, P75)] in Lanzhou City were 38.50 (26.00, 65.00) and 41.00 (29.00, 63.10) μg·m−3 in 2019 and 2020, respectively, and the difference was not statistically significant (Z=−0.989, P > 0.05). The average levels of the metal elements from high to low were: Al > Pb > Mn > As > Cd > Sb > Tl, and the annual average concentration of each metal element in 2019 was higher than that in 2020 (P<0.05). The M ( P25, P75) of PM2.5 concentrations in Chengguan and Xigu districts were 52.98 (17.00, 61.00) and 55.40 (17.00, 67.00) μg·m−3, respectively, with no statistically significant differences (P<0.05); the concentrations of Sb and Al in Chengguan District were lower than those in Xigu District (P<0.05), and the concentrations of other metal elements were not different between the two areas (P>0.05). There were seasonal differences in the concentrations of PM2.5 and seven metal elements in Lanzhou City (except PAl=0.007, the other Ps < 0.001). The results of the enrichment factor method showed that the EF values of the six metals (Sb, Al, As, Cd, Pb and Tl) were all greater than 1. Among them, except As, the EF values of other metal elements were all greater than 10, and the EF values of Al and Cd were both greater than 100. The results of principal component analysis showed that the variance contributions of the three principal components were 45.61%, 24.22%, and 14.42%, and the cumulative contribution reached 84.25%. The principal component 1 included Pb, As, Cd, and Sb, the principal component 2 included Al and Mn, and the principal component 3 contained Tl. The non-carcinogenic risks of the five metals were, in descending order, Al > Mn > Pb > Tl > Sb, among which the HQ values of the remaining four metals were less than 1 for adults and children, except the HQ value of Al for adults, which was greater than 1. The ILC values of carcinogenic metal As for adult males, adult females, and children were 2.68×10−5, 2.51×10−5, and 1.45×10−5, respectively; the ILC values of carcinogenic metal Cd for adult males, adult females, and children were 1.53×10−6, 1.43×10−6, and 8.26×10−7, respectively. Conclusion There is pollution of atmospheric PM2.5 and its adsorbed metal elements in Lanzhou. As and Cd elements may pose potential carcinogenic risks to the residents.
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Objective:To investigate the clinical efficacy and prognostic factors of surgical resection for gallbladder carcinoma.Methods:The clinicopathological data of 115 patients with gallbladder cancer treated by surgical operation in the First Affiliated Hospital of USTC (Anhui Provincial Hospital) from Dec 2015 to Dec 2020 were retrospectively analyzed. Follow-up was ended on Sep 30, 2021.Results:Tumor detection rate by ultrasonography, CT and MRCP were 64.7% (55/85), 83.3% (55/66) and 48.4% (31/64), respectively. All patients underwent surgical exploration, among which 76 patients underwent radical surgery and 39 did palliative surgery. Patients were followed up for 10-69 months, and the median survival time was 22 months. The overall survival rates at 1, 3 and 5 years were 67.4%, 31.2% and 28.4%, respectively. Univariate analysis showed that the degree of tumor differentiation, CA19-9, tumor size, nerve invasion, vascular invasion, lymph node metastasis, and T stage were correlated with the prognosis. Multivariate analysis showed that increased CA19-9, T stage, and lymph node metastasis were independent risk factors of the prognosis.Conclusion:Early diagnosis of gallbladder carcinoma is difficult, radical surgical treatment is preferred, and the overall prognosis is poor, CA19-9, T staging and lymph node metastasis are closely related to the prognosis.
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Objective:To analyze the efficacy and safety of radium-223 in the treatment of metastatic castration resistant prostate cancer (mCRPC).Methods:The clinical data of 22 patients with mCRPC treated with radium-223 in the Chongqing University Cancer Hospital from January 2021 to January 2022 were analyzed retrospectively. The average age was (70.7±1.3)years old. There were 7 cases with ECOG score of 1 and 15 cases with ECOG score of 2. There were 7 cases with grade 2 and 15 cases with grade 3 bone metastasis. For mCRPC, 1 case (4.6%) received first-line treatment, 4 cases (18.2%) received second-line treatment, 10 cases (45.5%) received third-line treatment, 4 cases (18.2%) received fourth-line treatment, and 3 cases (13.6%) received fifth-line treatment. The median time from the diagnosis of mCRPC to the start of radium-223 treatment was 29 (20, 34) months. Radium-223 (55kbq/kg) was injected intravenously every 4 weeks for up to 6 cycles. Before treatment, the median alkaline phosphatase (ALP) was 147.0 (101.8, 212.5)U/L, the median prostate specific antigen (PSA) was 44.7(20.2, 99.1)ng/ml, and 6 patients (27.3%) were complicated with grade 1-2 anemia. The median hemoglobin was 115.0 (103.8, 122.5) g/L, the average neutrophil was (3.0 ± 0.3)×10 9/L, and the average platelet was (169.8 ± 17.0)×10 9/L. The overall survival (OS), radiographic progression-free survival time (rPFS), time to PSA progression, PSA response rate, pain response rate, and time to pain progression were analyzed. Stratified analysis was carried out according to the number of treatment lines experienced before radium-223 treatment. At the same time, the main adverse reactions during radium-223 treatment were analyzed. Results:The mean number of treatment courses with radium-223 was 2.7(ranging 1 to 6), with 4 patients completing 6 courses, 12 (54.6%) completing ≥ 3 courses, and 10 (45.5%) completing < 3 courses. Thirteen patients (59.1%) were treated with radium-223 alone and 9 (40.9%) in combination with other treatments (1 of docetaxel chemotherapy, 2 of enzalutamide, 3 of olaparib, and 3 of estramustine phosphate). None of the patients in this group were treated with bisphosphonates. Ten patients (45.5%) in this group died, all due to disease progression. The median overall survival time of the 22 cases was 11.0 (2.2, 19.8) months. Three patients (13.6%), 7 patients (31.8%), 3 patients (13.6%), and 1 patient (4.5%) showed radiographic progression at 2, 3, 4, and 10 months after treatment, respectively, while the remaining 8 patients (36.4%) did not show radiographic progression during the follow-up period, and the median radiographic progression free time for the 22 patients was 4.0 (3.1, 4.9) months. There were four cases (18.2%) showed PSA response, of which three cases (13.6%) showed PSA rising again later, and one case (4.5%) showed continuous PSA decline. The median time to PSA progression for the 22 patients was 3.6 (2.2, 5.1) months. Fifteen patients (68.2%) experienced pain response at 1 month of treatment, of whom 5 (22.7%) experienced increased pain later and 10 (45.5%) experienced sustained pain relief. The median time to pain progression was 5.5 (3.5, 7.6) months in 22 patients. No patients received radiotherapy or surgery for pain, and no patients experienced fracture. In this group, 7 patients (31.8%) had a post-treatment ALP decrease ≥30% from baseline. Major adverse events during radium-223 treatment were all grade 1 to 2 events, no grade ≥3 adverse events, and no treatment discontinuers due to adverse events.Conclusions:Radium-223 resulted in high pain response rates and prolonged OS, rPFS and time to PSA progression in patients with mCRPC. Adverse effects were low during treatment. The conclusions need to be validated by further expansion of the sample size and extended follow-up.
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Objective:To evaluate the safety and efficacy of trimodality treatment (TMT) which is complete transurethral resection of bladder tumor with concurrent radiotherapy and chemotherapy for invasive bladder cancer.Methods:From Mar. 2016 to Oct.2021, patients who were indicated of radical cystectomy (RC) but refused were enrolled to TMT treatment prospectively. Inclusive criteria were: ① the patients refused radical surgery; ② male or female, no older than 80 years; ③ no matter the tumor size, the bladder tumor be completely resected by transurethral surgery, and the hydronephrosis be improved after resecting the tumor; ④ the postoperative pathology of urothelial carcinoma; ⑤ recurrent T 1 and high-grade non-muscle invasive bladder cancer (NMIBC) or T 2-4a muscle invasive bladder cancer (MIBC); ⑥ no definitive metastasis in preoperative chest, abdominal CT or MRI; ⑦ hemoglobin ≥100 g/L, white blood cell count ≥4×10 9/L, platelet count ≥100×10 9/L, and normal liver and renal function. The exclusion criteria were: ① tumor invading bladder neck or anterior or posterior urethra; ② bladder contracture or severe urethral stricture; ③ regional lymph node metastasis or distant metastasis by imaging examination; ④ no improvement of hydronephrosis after resection; ⑤ definitive contraindications of radiotherapy or chemotherapy; ⑥ uncontrolled hypertension, diabetes, coronary heart disease or other severe diseases. After cTURBT, paclitaxel (50 mg/m 2 on Day 1 of each week) combined with cisplatin(20 mg/m 2 on day 1-2 of each week)was administered with concurrent radiotherapy (2 Gy/fraction/day) for 4 weeks. If cystoscopy and/or radiographic detected no recurrence or metastasis, the patients were treated with concurrent chemoradiotherapy for 2 and a half weeks (total dose of 64 Gy). The side effects of radiotherapy and chemotherapy during TMT were observed, the quality of life(QOL)was evaluated by FACT-P scale, and the bladder recurrence, distant metastasis and survival were assessed with imaging and cystoscopy. From March 2016 to October 2021, 79 patients with RC were enrolled, including 67 males and 12 females, aged 44-86 years. The pathology of RC was urothelial carcinoma of the bladder. There was no definitive lymph node or distant metastasis in preoperative imaging. The progress and survival after TMT and RC treatment were followed up and the survival rates were calculated by Kaplan-Meier method. Results:Of the 30 patients who underwent TMT, including 25 males and 5 females, aged 32-76 years, there were 7 cases of cT 1 (23.3%), 19 cases (63.3%) of cT 2, 2 cases of cT 3 (6.7%)and 2 cases of cT 4(6.7%), respectively. A total of 132 adverse events of all grades of chemoradiotherapy occurred, of which only 4 were grade Ⅳ, with no bowel leakage or death due to complications. The mean scores of negative questions in FACT-P were 3.22±0.67, 1.30±0.63 and 0.87±0.69 before TMT treatment, 6 and 12 months after TMT treatment, respectively. The quality of life was significantly improved( F=129.081, P<0.001), and the rate of bladder preservation was 86.7%(26/30). Two cases underwent salvage RC(6.7%)and 2 cases died of bladder recurrence(6.7%). There were 8, 4 and 2 patients survived 4, 5 and 6 years, respectively. Seven cases (23.3%) had bladder recurrence, 3 cases (10.0%) underwent distant metastasis and 6 patients (20.0%)died after TMT because of the progression. The 1, 2 and 5 year overall survival rates by TMT treatment were 88.89%, 82.96% and 62.77%, respectively. Median follow-up was 19.5(6.8-44.5) months in the TMT group and 35.5(18.8-53.3) months in the RC group ( z=-1.998, P=0.046). Progression-free survival in the TMT and RC group were 66.7% and 80.0%( χ2=1.047, P=0.306), and the overall survival rates were 80.0% and 80.0% ( χ2=0.482, P=0.488) respectively. The difference was not statistically significant. Conclusions:The TMT is a safe and effective alternative for RC, which can improve the quality of life and control the tumor sufficiently.
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Cancer is considered as one of the major diseases endangering human health in the world, it is urgent to find a safer and more efficient treatment for cancer therapy. Gene therapy with ribonucleic acid (RNA) drugs could regulate the expression of tumor related genes, and exhibit good anti-tumor therapeutic potential in preclinical and clinical trials. Based on the differences between tumor tissues and normal tissues in microenvironment signal characteristics such as pH, specific enzyme concentration or redox gradient, various microenvironment responsive nanocarriers had been studied and developed to deliver RNA drugs to tumor tissues and cells, improving the anti-tumor efficacy of RNA drugs and reducing toxic and side effects. This paper reviews the pathophysiological characteristics of tumor microenvironment and various strategies of tumor microenvironment responsive nanocarriers, in order to provide reference for the design of safe and efficient RNA drug delivery system for cancer therapy.
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Objective:To explore the therapeutic mechanism of Mongolian medicine Sendeng-4 decoction for rheumatoid arthritis by 99Tc m-hydrazinonicotinamide-(polyethylene glycol) 4-E[(polyethylene glycol) 4-c((Arg-Gly-Asp)fk)] 2 (3PRGD 2) imaging. Methods:A total of 200 female SD rats (age: 6-7 weeks) were divided into collagen-induced arthritis (CIA) group ( n=176) and blank control group ( n=24). Rats in the CIA group were divided into Sendeng-4 decoction treatment group ( n=24), etanercept treatment group ( n=24), and negative control group ( n=24) by simple random sampling method. 99Tc m-3PRGD 2 SPECT/CT imaging was performed before and after modeling and treatment. The differences of target/non-target (T/NT) ratio and serological, pathological, and immunohistochemical results among groups were compared by one-way analysis of variance or Kruskal-Wallis rank sum test. The correlation was analyzed by Pearson correlation or Spearman correlation analysis. Results:There were 95 (95/176) CIA models successfully established. The T/NT ratios of Sendeng-4 decoction treatment group and etanercept treatment group were lower than that of negative control group (0.260± 0.094, 0.238±0.099, 0.766±0.144 ; F=163.00, P<0.001), while there was no significant difference between the two drug treatment groups ( P>0.05). After drug treatment, serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α) and α vβ 3 were significantly lower than those of negative control group ( F values: 49.43-92.36, all P<0.001), pathological score was also lower than that of negative control group ( H=34.25, P<0.001), and levels of immunohistochemical makers (VEGF, TNF-α, α vβ 3, CD31, CD34) were also lower than those of negative control group ( H values: 13.51-26.84, all P<0.001), while there were no significant differences between the two drug treatment groups (all P>0.05). The T/NT ratios were positively correlated with above indictors in Sendeng-4 decoction treatment group ( r values: 0.56-0.59, rs values: 0.49-0.69), etanercept treatment group ( r values: 0.50-0.55, rs values: 0.46-0.70) and negative control group ( r values: 0.55-0.80, rs values: 0.58-0.86, P<0.001 or P<0.05). Conclusion:Verified by 99Tc m-3PRGD 2 SPECT/CT imaging and molecular pathology, Mongolian medicine Sendeng-4 decoction can inhibit neovascularization by down-regulating vascular factors such as VEGF, resulting in delaying the progression of the disease and improving clinical symptoms.
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ImmunoPET imaging, which combining the specificity of monoclonal antibody and high sensitivity of PET imaging, blazes new trails of molecular imaging modality. In recent years, clinical translation and application of immunoPET imaging strategies have been flourishing, as a result, facilitating early and non-invasive diagnosis of numerous human tumors, patient stratification before monoclonal antibody therapy and radiation dose estimation prior to radioimmunotherapy. Here, we summarize the most recent clinical evidence of immunoPET in tumor diagnosis and therapy.
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Objective:To prepare 89Zr labeled Daratumumab and evaluate its feasibility in the imaging diagnosis of multiple myeloma (MM). Methods:According to the principle of 89Y (p, n) 89Zr nuclear reaction, 89Zr was produced by cyclotron solid target system (30 μA, 1.5 h) and automatic purification module. The radionuclide purity, half-life and impurity metal ion concentration were detected. Desferrioxamine (DFO) was coupled with Daratumumab and then chelated with 89Zr to prepare 89Zr-DFO-Daratumumab. The quality control analyses of three consecutive batches were carried out. Pharmacokinetic evaluation and 89Zr-DFO-Daratumumab microPET/CT imaging were performed in normal rabbits and orthotopic myeloma mouse models, respectively. The SUV in situ myeloma and that in normal bone were compared by independent-sample t test. Results:About 560 MBq of 89Zr was obtained, and there were only two characteristic energy peaks of 89Zr (909 keV and 511 keV) by γ spectrometer. The half-life of 89Zr was 78.2 h, and the content of metal impurities was small. 89Zr-DFO-Daratumumab was prepared with pH of 7.2, radiochemical purity of more than 99%, good stability in vitro, and sterility and endotoxin tests were passed. Pharmacokinetic studies in rabbits showed that 89Zr-DFO-Daratumumab was gradually distributed from blood to liver, spleen, kidney and bone joints over time and metabolism. The results of microPET/CT imaging in orthotopic myeloma mouse models showed that the SUVs of 89Zr-DFO-daratumumab in situ myeloma were significantly higher than those in normal bone (2 h: 0.22±0.02 vs 0.06±0.00; 1 d: 0.38±0.01 vs 0.08±0.00; t values: 8.89, 21.90, both P=0.001). Conclusion:89Zr and 89Zr-DFO-daratumumab are successfully prepared, and relevant quality control and biological evaluation in vivo and in vitro are completed, which verify the feasibility of 89Zr-DFO-Daratumumab in the imaging diagnosis of MM, thus laying a foundation for clinical transformation.
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Objective:To assess the imaging characteristics of muscle FDG metabolism, tumor incidence, and pulmonary interstitial changes in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody positivity in 18F-FDG PET/CT imaging, and the value of 18F-FDG PET/CT in differentiating anti-MDA5 antibody positive dermatomyositis. Methods:From June 2016 to July 2019, the PET/CT images of 75 patients with dermatomyositis (21 males, 54 females, age (52.3±14.3) years; 34 anti-MDA5 antibody positive and 41 anti-MDA5 antibody negative) and 30 healthy controls (10 males, 20 females; age (53.5±11.8) years) were retrospectively analyzed in Renji Hospital, School of Medicine, Shanghai Jiao Tong University. The SUV max of muscle was measured and the mean of SUV max (mSUV max) was calculated. Statistics of patients with dermatomyositis complicated with neoplastic lesions and the SUV max of pneumonia lesions in patients with dermatomyositis complicated with interstitial pneumonia was determined. Independent sample t test, one-way analysis of variance, Student-Newman-Keuls (SNK) test and χ2 test were used to analyze data. The ROC curve analysis was used to analyze the diagnostic efficacy of mSUV max for the differential diagnosis of anti-MDA5 antibody positive dermatomyositis. Results:The muscle mSUV max of the control group, anti-MDA5 antibody positive and negative groups were 0.39±0.05, 0.66±0.21 and 0.87±0.29 ( F=39.93, P<0.001), respectively. The muscle mSUV max of dermatomyositis patients was increased compared with healthy controls ( q values: 6.76, 12.63, both P<0.001), and the muscle mSUV max of anti-MDA5 antibody negative was higher than positive ( q=5.79, P<0.001). The AUC was 0.74, and the cut-off value of muscle mSUV max was 0.75 with the accuracy of 74.7%(56/75). Of 41 patients with negative anti-MDA5 antibody, there were 6 (14.6%) had malignant tumor, while there was no malignant tumor in patients with positive anti-MDA5 antibody (0/34; χ2=5.41, P=0.020). There were 11 patients (26.8%, 11/41) with anti-MDA5 antibody negative dermatomyositis complicated with interstitial pneumonia and 33 patients (97.1%, 33/34) with anti-MDA5 antibody positive dermatomyositis complicated with interstitial pneumonia ( χ2=37.81, P<0.001). FDG metabolism in anti-MDA5 antibody positive patients was higher than that in anti-MDA5 antibody negative patients (lesion SUV max: 3.65±1.83 and 2.38±1.27; t=2.13, P=0.039). Conclusions:The muscle FDG metabolism of anti-MDA5 antibody positive dermatomyositis patients is higher than that of healthy controls, but lower than that of anti-MDA5 antibody negative patients. The incidence of neoplastic lesions in patients with positive anti-MDA5 antibody is lower than that in patients with negative anti-MDA5 antibody. The proportion and severity of interstitial pneumonia are higher in patients with positive anti-MDA5 antibody than in those with negative anti-MDA5 antibody. 18F-FDG PET/CT has certain value on identifying anti-MDA5 antibody positive dermatomyositis.
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Objective:To explore the application value of three-dimensional visualization technology in the analysis of anatomic variation of peripancreatic vessels in patients with pancreatic space occupation.Methods:A total of 98 cases in Yijishan Hospital of Wannan Medical College, the First Affiliated Hospital of University of Science and Technology of China, the First Affiliated Hospital of Anhui Medical University, the Second Affiliated Hospital of Anhui Medical University, the First Affiliated Hospital of Bengbu Medical College, Fuyang People's Hospital from June 2018 to December 2019 were retrospectively analyzed. Of 94 patients were enrolled, including 56 males and 38 females, aged (61.2±7.2) years. Abdominal organs and blood vessels were reconstructed by 3D visualization technology, and anatomic variation of peripancreatic vessels was analyzed, including abdominal trunk, hepatic artery system, portal vein system and dorsal pancreatic artery.Results:The three-dimensional reconstruction rate of celiac trunk vessels was 100.0% (94/94). The 60 cases of abnormal celiac trunk were as follows: liver and spleen trunk in 5 cases (5.3%), stomach and spleen trunk in 1 case (1.1%), liver, stomach and spleen mesentery trunk in 3 cases (3.2%), liver, stomach and spleen mesentery trunk in 17 cases (18.1%), celiac trunk with one or more inferior phrenic arteries in 34 cases (36.2%). There were 69 cases (73.4%) of Michels type Ⅰ, 2 cases (2.1%) of Michels type Ⅲ, 1 case (1.1%) of Michels Ⅴ, 2 cases (2.1%) of Ⅷ, and 1 case (1.1%) of type Ⅸ of hepatic artery system. There were 17 cases (18.1%) of accessory left hepatic artery from celiac trunk which did not belong to Michels classification. Left accessory hepatic artery originated from left gastric artery and left hepatic artery originated from superior mesenteric artery in 1 case (1.1%), right accessory hepatic artery originated from celiac trunk combined with proper hepatic artery and right anterior hepatic artery combined with gastroduodenal artery originated from right posterior hepatic artery in 1 case (1.1%). Abnormal walking of dorsal pancreatic artery in 3 cases. The inferior mesenteric vein flowed into the superior mesenteric vein in 38 cases (40.4%), and the inferior mesenteric vein flowed into the splenic vein and superior mesenteric vein in 4 cases (4.3%).Conclusion:Three-dimensional visualization technique is helpful to determine the variation of peripancreatic vessels, and has certain significance for accurate preoperative evaluation and surgical guidance of patients with pancreatic space occupation.