The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear. @*Materials and Methods@#Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software. @*Results@#Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031). @*Conclusion@#This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

Value of chitinase-like protein YKL-40 in bronchoalveolar lavage fluid for predicting refractory / 中国当代儿科杂志

OBJECTIVE@#To evaluate the value of chitinase-like protein YKL-40 in bronchoalveolar lavage fluid (BALF) for predicting refractory @*METHODS@#A total of 50 children with common @*RESULTS@#Compared with the common MPP group, the RMPP group had significantly higher incidence rates of fever, shortness of breath, lung consolidation, and pleural effusion (@*CONCLUSIONS@#There is an increase in the level of YKL-40 in BALF in children with RMPP, and the level of YKL-40 in BALF has a certain value for predicting RMPP.

Biopathway construction of plant natural products / 药学学报

Plant natural products (PNPs) are important sources of innovative drugs. They are mainly obtained by isolation or extraction from plants. Low content and with structural analogues in plants result in high production cost, which restricts the research and application of PNPs. While biopathway construction by synthetic biology provides an alternative for production of PNPs. By biosynthetic pathway analysis of PNPs and reconstructing the biopathway in microorganisms, we can produce PNPs in cell factories efficiently. Recently, several predominantly international reports about biosynthesis of PNPs and its synthetic biology production, triggered the researches of PNPs. Abundant traditional Chinese medicine resources and profound cultural heritage of Chinese medicine make biosynthesis pathway analysis of PNPs to be a research hotspot. And some of the studies have achieved significant progress. Here, recent progress in the biosynthesis of plant natural products and its synthetic biology was reviewed. In particular, the application of new methods and technologies in recent years were summarized and discussed. This will provide reference for the biopathway construction of plant natural products.

Molecular Mechanism of Salvia miltiorrhiza Quality Formation Based on Single Nucleotide Polymorphism of Functional Genes / 中国实验方剂学杂志

Objective:To investigate the relationship between the single nucleotide polymorphism（SNP）of function genes and effective components of <italic>Salvia miltiorrhiza</italic> and the molecular mechanism of specific quality formation of <italic>S. miltiorrhiza</italic>. Method:The fingerprints of components in <italic>S. miltiorrhiza</italic> from eight different habitats and varieties were obtained by high-performance liquid chromatography （HPLC）. The full-length cDNA of three functional genes<italic> </italic>acetyl-CoA C-acetyltransferase（<italic>SmAACT</italic>），4-diphosphocytidyl-2-C-methyl-<italic>D</italic>-erythritol kinase（<italic>SmCMK</italic>） and isopentenyl diphosphate isomerase（<italic>SmIPPI</italic>） in tanshinone metabolic pathway were amplified by polymerase chain reaction（PCR），cloned， and sequenced，followed by bioinformatics analysis. Result:The full-length cDNA sequences of three functional genes <italic>SmAACT</italic>，<italic>SmCMK</italic>， and <italic>SmIPPI</italic> in tanshinone metabolic pathway were obtained from 23 strains of <italic>S. miltiorrhiza</italic> from eight different habitats and varieties. As revealed by the analysis of SNP and amino acid polymorphisms of three functional genes，18，16， and 14 SNP sites were found respectively. HPLC results showed the samples from Beijing，Hubei，Shandong （No. SDB），Shanxi，Henan， and Shandong （No. SDZ） were clustered into one branch，and those from Hebei and Inner Mongolia were clustered into another branch， which suggested that the variation trend of <italic>S. miltiorrhiza</italic> components had little correlation with geographical distance，but the variety was a critical factor for the quality. Conclusion:There was an obvious genetic differentiation trend in <italic>S. miltiorrhiza</italic> from different habitats，and different origin-specific genotypes were formed. The molecular mechanism of the formation of the specific quality of <italic>S. miltiorrhiza</italic> from different habitats was discussed，which laid a foundation for the stability and effectiveness of clinical medication，and guided the breeding of excellent varieties of <italic>S. miltiorrhiza</italic>.

The Pattern of Time to Onset and Resolution of Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors in Cancer: A Pooled Analysis of 23 Clinical Trials and 8,436 Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The occurrence pattern of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) in cancer treatment remains unclear. @*Materials and Methods@#Phase II-III clinical trials that evaluated ICI-based treatments in cancer and were published between January 2007 and December 2019 were retrieved from public electronic databases. The pooled median time to onset (PMT-O), resolution (PMT-R), and immune-modulation resolution (PMT-IMR) of irAEs were generated using the metamedian package of R software. @*Results@#Twenty-two eligible studies involving 23 clinical trials and 8,436 patients were included. The PMT-O of all-grade irAEs ranged from 2.2 to 14.8 weeks, with the longest in renal events. The PMT-O of grade ≥ 3 irAEs was significantly longer than that of all-grade irAEs induced by programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) inhibitors (27.5 weeks vs. 8.4 weeks, p < 0.001) and treatment of nivolumab (NIV) plus ipilimumab (IPI) (7.9 weeks vs. 6.0 weeks, p < 0.001). The PMT-R of all-grade irAEs ranged from 0.1 to 54.3 weeks, with the shortest and longest in hypersensitivity/infusion reaction and endocrine events, respectively. The PMT-IMR of grade ≥ 3 irAEs was significantly shorter than that of all-grade irAEs caused by PD-1/PD-L1 blockade (6.9 weeks vs. 40.6 weeks, p=0.002) and NIV+IPI treatment (3.1 weeks vs. 5.9 weeks, p=0.031). @*Conclusion@#This study revealed the general and specific occurrence pattern of ICI-induced irAEs in pan-cancers, which was deemed to aid the comprehensive understanding, timely detection, and effective management of ICI-induced irAEs.

Russian Characteristic Medicinal Plant Resources Based on DNA Barcode Technology / 中国实验方剂学杂志

Objective::To investigate the distribution status of medicinal plants in the wild areas of Russian Caucasus and Altai, and clarify the types and efficacy information of medicinal plants in the area, so as to dig deep into new resources and new functions of medicinal plants in the countries along the Belt and Road. Method::Medicinal plants in the wild were searched and collected to make waxy specimens, and sent back to the country to extract the total DNA of the leaves of the leaves. Internal Transcribed Spacer(ITS)sequence universal primers were used for Polymerase Chain Reaction (PCR)amplification. The PCR products were sent for the two-way sequencing, and the sequencing results are spliced by software according to National Center for Biotechnology Information(NCBI). The same ITS sequence of the highest similarity species obtained by database BLAST was analyzed by DNAman software to identify the ITS sequence of the species and the ITS sequence of the same species. The MEGA 7 software was used as the phylogenetic tree, and the Kimura-2 parameter genetic distance was used to construct the neighbor joining(NJ) phylogenetic tree by the neighbor-joining method. The confidence of each branch of the development tree was tested by the bootstrap test method. A total of 2 000 cycles were performed, and the results were identified based on the clustering results. On this basis, the key medicinal plants in the Russian Caucasus and Altay wild areas were summarized and analyzed. Result::After BLAST alignment in NCBI database, the ITS sequences of each specimen were clustered with the login sequences on the NCBI database, which were separated from the outer group. The species classification of the specimens to be identified was determined by combining the characteristics of the specimens. A total of 51 plants were identified from the specimens collected in the field, covering 44 genera of 17 families, and 29 plants had clear efficacy records. The National Drug List of the Russian Federation and the Chinese Pharmacopoeia were retrieved to summarize commonly used medicinal plants in China and conclude that 20 kinds of Chinese and Russian common medicinal materials have different medicinal effects in local areas. This study has a reference significance for expanding the scope and clinical experience of traditional Chinese medicines, and provides a basis for strengthened local species conservation, development and utilization of wild medicinal plant resources.

The evolution of the nasopharyngeal carcinoma staging system over a 10-year period: implications for future revisions / 中华医学杂志(英文版)

BACKGROUND@#The classification criteria and staging groups for nasopharyngeal carcinoma described in the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system have been revised over time. This study assessed the proportion of patients whose staging and treatment strategy have changed due to revisions of the UICC/AJCC staging system over the past 10 years (ie, from the sixth edition to the eighth edition), to provide information for further refinement.@*METHODS@#We retrospectively reviewed 1901 patients with non-metastatic nasopharyngeal carcinoma treated in our cancer center between November 2009 and June 2012. The Akaike information criterion and Harrell concordance index were applied to evaluate the performance of the staging system.@*RESULTS@#In total, 25 (1.3%) of the 1901 patients who were staged as T2a according to the sixth edition system were downgraded to T1 in the eighth edition; 430 (22.6%) staged as N0 in the sixth edition were upgraded to N1 in the eighth edition; 106 (5.6%) staged as N1/2 in the sixth edition were upgraded to N3 in the eighth edition. In addition, 51 (2.7%) and 25 (1.3%) of the study population were upstaged from stage I to stage II and stage II to stage IVa, respectively; 10 (0.5%) was downgraded from stage II to stage I. The survival curves of adjacent N categories and staging groups defined by eighth classification system were well-separated. However, there was no significant difference in the locoregional failure-free survival (P = 0.730) and disease-free survival (P = 0.690) rates between the T2 and T3 categories in the eighth edition classification system.@*CONCLUSIONS@#Modifications to the tumor-node-metastasis staging system over the past 10 years have resulted in N classification changes in numerous cases. Although the eighth edition tumor-node-metastasis staging system better predicts survival outcomes, the T classification could be simplified in future revisions.

Effects of acupuncture, combined with phacoemulsification for cataract with glaucoma / 中国针灸

OBJECTIVE@#To observe the effects of acupuncture combined with phacoemulsification for cataract with glaucoma.@*METHODS@#Sixty-eight patients with cataract and angle-closure glaucoma were randomly divided into an observation group and a control group, 34 cases in each one. The patients in the control group were treated with phacoemulsification. Based on the treatment in the control group, the patients in the observation group were treated with and acupuncture at acupoints around eyes; the treatment was given once every other day, and 15-day treatment constituted a course, and 2 courses (60 days) were given. The intraocular pressure (IOP), visual acuity, pain severity, aqueous outflow (F value) and clinical symptoms were observed in the two groups before treatment and after 1 d, 7 d, 30 d and 60 d of treatment.@*RESULTS@#The IOP after 1 d, 7 d, 30 d and 60 d of treatment in the observation group was lower than that in the control group (all <0.05), while the visual acuity after 7 d, 30 d and 60 d of treatment in the observation group was higher than that in the control group (all <0.05). Compared before treatment, the IOP was significantly decreased after 1 d, 7 d, 30 d and 60 d of treatment in the two groups, and the visual acuity was significantly increased after 7 d, 30 d and 60 d of treatment in the two groups (all <0.05). The pain scores and F value after 7 d, 30 d and 60 d of treatment in the observation group were lower than those in the control group (all <0.05). Compared before treatment, the pain scores and F value after 7 d, 30 d and 60 d of treatment were significantly reduced in the two groups (all <0.05). After 60 d of treatment, the number of patients who presented general clinical symptoms in the observation group was significantly lower than that in the control group (<0.05).@*CONCLUSION@#Based on phacoemulsification, acupuncture and could significantly reduce the IOP and F value, relieve pain and improve visual acuity in patients with cataract and glaucoma.

Hypoglycemic Mechanism of Ziya Biti Tablet Based on LC-MS Metabolomics Technique / 中国实验方剂学杂志

Objective: To observe the hypoglycemic effect of Uygur medicine Ziya Biti tablet on the type 2 diabetic rats, and analyze the hypoglycemic mechanism based on metabolomic techniques. Method: According to the results of clinical research about different origins of Ziya Biti tablet, the optimal composition was screened out; type 2 diabetic rats were taken as an experimental object in the pharmacodynamic experiments;the control group and model group were given the same dose of normal saline, Ziya Biti bablet group was given 300 mg·kg-1, the metformin group was given 300 mg·kg-1 metformin hydrochloride. The fasting blood and weight changes of the experimental group after the treatment were recorded and compared with normal group; ultra-high performance liquid chromatography-linear ion trap/electrostatic field orbit trap combined-type high resolution mass spectrometry (UHPLC-LTQ/Orbitrap MS) technology was used to conduct the metabolomics analysis on the rat serum, and principal component analysis (PCA), partial least squares discriminant analysis (OPLS-DA) on different groups of rat serum metabolites were performed to identify potential biomarkers. Result:Compared with the model group, the rats in the Uygur medicine Ziya Biti tablet showed a healthy states, and the blood glucose were decreased(PPPConclusion:The experimental results showed that Uygur medicine Ziya Biti tablet can reduce the blood glucose of type 2 diabetic rats and allivate general physiological characteristics. The mechanism of action may be related to the improvement of amino acid metabolism and lipid metabolism.

Safety and efficacy of a microneedle fractional radiofrequency for facial photoaging / 中华医学美学美容杂志

Objective Microneedle fractional radiofrequency (MFR) is a novel method for reju-venation that combines radiofrequency and microneedles .The aim of this study was to evaluate pro-spectively the efficacy and safety of MFR in the treatment of facial photoaging .Methods Between De-cember 2017 and December 2018 ,a total of 24 female subjects with facial photoaging aged 45 to 60 (45 .9 ± 8 .7)years ,the course of 1 to 20 (8 .88 ± 5 .06) years ,were collected from the Department of Dermatology ,Pepole's Hospital of Xinjiang Uygur Autonomous Region .They received 3 treatments at 4-week intervals .Global scores for photoaging (GSP) were evaluated at baseline ,after 1 treatment and 3 treatments respectively .Facial wrinkles ,skin texture ,pigmentation ,telangiectasia ,and skin tightness were evaluated by the 4-point method after 1 treatment and 3 treatments respectively .Visual analogue scale (VAS) was used for self-assessment of pain during treatment .At the third treatment self assessment on the degree of satisfaction with therapeutic effects was conducted in subiects .The adverse reactions were evaluated at every treatment immediately and the third day and seventh day .Results The GSP score of 24 subjects before treatment was (2 .83 ± 0 .92) ,(2 .25 ± 0 .95) after 1 treatment ,and (1 .67 ± 0 .48) after 3 treatments .The difference between before and after 1 treatment was statistically significant (t = 2 .17 , P < 0 .05) ,and between before and after 3 treatments , the difference was statistically significant (t = 5 .52 , P < 0 .05) .There were statistically significant differ-ences in facial wrinkles ,skin texture and skin tightness improvement scores between the first treat-ment and the third treatment (t = 5 .48 ,3 .88 ,5 .46 , P < 0 .05) .There were statistically significant differences in pigmentation and telangiectasia scores between the first treatment and the third treat -ment (t = 2 .46 and 2 .17 ,P < 0 .05) .After the third treatment ,the VAS value was 3 .2 ± 1 .2 ,indica-ting mild to moderate pain .The total satisfactory rate of the 24 subjects was 83 .33％ .The subjects had no adverse reactions .Conclusions MFR can effectively improve the symptoms of facial photoaging without obvious adverse reactions .

Neutropenia during the First Cycle of Induction Chemotherapy Is Prognostic for Poor Survival in Locoregionally Advanced Nasopharyngeal Carcinoma: A Real-World Study in an Endemic Area / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the effect of neutropenia during the first cycle of induction chemotherapy (IC-1) on survival in locoregionally advanced nasopharyngeal carcinoma (LANPC). MATERIALS AND METHODS: Eligible patients (n=545) with LANPC receiving IC+concurrent chemoradiotherapy were included. Based on nadir neutrophil afterIC-1, all patientswere categorized into three groups: no/grade 1-2/grade 3-4 neutropenia. Five-year overall survival (OS) and disease-free survival (DFS) were compared between groups and subgroups stratified by IC regimen. We also explored the occurrence of IC-1–induced myelosuppression events and the minimal value of post-treatment neutrophil-to-lymphocyte ratio (post-NLRmin). Univariate/multivariate analyses were performed to investigate the effect of IC-1–induced neutropenia, timing of neutropenia, number of myelosuppression events, and high post-NLRmin on OS/DFS. RESULTS: Grade 1-2/grade 3-4 neutropeniawere associatedwith poorer OS/DFS than no neutropenia (all p < 0.05); OS/DFS were not significantly different between patients experiencing grade 1-2 vs. 3-4 neutropenia. Neutropenia had no significant effect on OS/DFS in patients receiving docetaxel–cisplatin–5-fluorouracil (TPF). Grade 1-2 (grade 3-4) neutropenia negatively influenced OS/DFS in patients receiving cisplatin–5-fluorouracil (PF) (PF and docetaxel–cisplatin [TP]; all p < 0.05). Neutropenia, two/three myelosuppression events, and high post-NLRmin (≥ 1.33) was most frequent on days 5-10, second and third week of IC-1, respectively. After adjustment for covariates, IC-1–induced neutropenia, two/three myelosuppression events, and post-NLRmin ≥ 1.33were validated as negative predictors of OS/DFS (all p < 0.05); timing of neutropenia had no significant effect. CONCLUSION: Occurrence of neutropenia, number of myelosuppression events, and high post-NLRmin during PF/TP IC-1 have prognostic value for poor survival in LANPC.

A National Study of Survival Trends and Conditional Survival in Nasopharyngeal Carcinoma: Analysis of the National Population-Based Surveillance Epidemiology and End Results Registry / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Conditional survival (CS) provides important information on survival for a period of time after diagnosis. Currently, information on CS patterns of patients with nasopharyngeal carcinoma (NPC) is lacking. We aimed to analyze survival rate over time and estimate CS for NPC patients using a national population-based registry. MATERIALS AND METHODS: Patients diagnosed with NPC between 1973 and 2007 with at least 5-year follow-up were identified from the Surveillance Epidemiology End Results registry. Traditional survival rates and crude CS estimateswere calculated using Kaplan-Meier analysis. Risk-adjusted survival curves were plotted from the proportional hazards model using the correct group prognosis method. RESULTS: For 7,713 patients analyzed, adjusted baseline 5-year overall survival improved significantly from 36.0% in patients diagnosed in 1973-1979, 41.7% in 1980-1989, 46.6% in 1990-1999, to 54.7% in 2000-2007 (p < 0.01). CS analysis demonstrated that for every additional year survived, adjusted probability of surviving the next 5 years increased from 66.7% (localized), 54.0% (regional), and 35.3% (distant) at the time of diagnosis, to 83.7% (localized), 75.0% (regional), and 62.2% (distant) for patients who had survived 5 years. Adjusted 5-year CS differed among age, sex, tumor histology, ethnicity, and stage subgroups initially, but converged with time. CONCLUSION: Treatment outcomes of NPC patients have greatly improved over the decades. Increases in CS become more prominent in patients with distant disease than in those with localized or regional disease as patients survive longer. CS provides more dynamic prognostic information for patients who have survived a period of time after diagnosis.

Improving qualified rate of cleaning of loaner orthopedic surgery instruments by application of quality control circle / 中国感染控制杂志

Objective To improve the qualified rate of cleaning of loaner orthopedic surgery instruments by application of quality control circle(QCC).Methods QCC activity was carried out in a hospital from May to October 2016, on-site assessment of cleaning quality was performed by two circle members, causes of unqualified cleaning result of loaner orthopedic surgery instruments were recorded, the qualified result of loaner orthopedic surgery instruments before QCC activity(May-June 2016)and after QCC activity(September-October 2016)was compared. Results Before QCC activity, there were 1 667 packages of loaner instruments, 1 415 were qualified for cleaning, qualified rate was 84.88％;after activity, there were 1 673 packages of loaner instruments, 1 655 were qualified for cleaning, qualified rate was 98.92％, difference was statistically significant between two groups(P＜0.01), qualified rate increased to 14.04％, target achievement rate was 116％.Conclusion Application of the scientific tool of QCC can improve the qualified rate of cleaning of loaner orthopedic surgery instruments.

Application of muscular flap and induced membrane technique in the emergency treatment for limb salvage for Gustilo type Ⅲ B and Ⅲ C open fracture of lower leg / 中华显微外科杂志

Objective To investigate the clinical effectivity of the muscular flap transposition and induced membrane technique in the emergency treatment for the limb salvage of Gustilo type Ⅲ B/C open fracture of lower leg. Methods From July, 2015 to December, 2017, 10 cases of Gustilo type Ⅲ B/C fracture of lower leg with bone defects were performed limb salvage surgery. Induced membrane technique was used to fill the bone defects in the emergency room.The gastrocnemius and/or soleus muscular flaps were transposed to cover the bone cement or ex-posed bone simultaneously in emergence treatment. After the wound healed completely, traditional bone grafting was used to repair the bone defects. There were 4 cases of Gustilo type Ⅲ B and 6 cases of Gustilo type Ⅲ C. The aver-age length of bone defect was (5.25±1.70) cm ranging from 3.0 cm to 11.0 cm. The gastrocnemius medial head flaps were performed in 5 cases, the combined application with the gastrocnemius medial head flaps and the medial hemimuscular flaps of soleus were performed in 2 cases, and medial hemimuscular flaps of soleus were transposed in 3 cases. Results The wounds in 6 cases were healed at one stage, but 2 cases healed by dressing because the exudate after skin grafting.In 1 case, the cross-leg flap was used to cover the exposed bone cement due to the necro-sis of soleus flap. The other 1 was performed the transposition of the lateral gastrocnemius flaps because the exposure of bone cement after the necrosis of the upper and lateral muscles in lower leg. In the second-stage, the bone defects were reconstructed by traditional bone grafting. The average healed time of bone was 7.2 months ranging from 5 months to 9 months. At the last followed-up time, all patients recovered their function of weight-bearing. The Paley's score of the adjacent joints: excellent in 8 cases and good in 2 cases. Conclusion The combination with induced membrane technique and local muscular flap transposition in emergency surgery is an effective method to limb salvage for the Gustilo type Ⅲ B/C open fracture of lower leg.

Clinical observation of osteotomy and fusion for the treatment of severe rigid equinus deformity / 中国骨伤

<p><b>OBJECTIVE</b>To explore clinical efficacy of osteotomy and fusion in treating severe rigid equinus deformity.</p><p><b>METHODS</b>From April 2010 to October 2015, 13 patients(16 feet) with severe rigid equinus deformity were treated with osteotomy and fusion by hollow screw, including 6 males and 7 females aged from 39 to 62 years old with an average of(49.6±5.3) years old;the courses of diseases ranged from 5 to 27 years with an average of (9.0±4.8) years. Six patients (9 feet) were treated with osteotomy and fusion for three joints, 4 patients(4 feet) were treated with osteotomy and fusion for four joints, and 3 patients (3 feet) were treated with osteotomy and fusion for tibiotalar and calcaneal-talar joints. All patients manifested as foot pain, heel could not touch floor and walking before operation. Postoperative complications were observed, AOFAS score were applied to evaluate clinical effect.</p><p><b>RESULTS</b>Thirteen patients were followed up from 18 to 24 months with an average of 20 months. Only one patient occurred local skin necrosis after operation and healed by dressing change and anti-infective therapy. All feet obtained fracture healing, the time ranged from 12 to 16 weeks with an average of 13.2 weeks. AOFAS score were improved from 11.85±10.66 before operation to 81.38±3.69 after operation, and had significant difference(=-25.67, <0.05);15 feet good and 1 foot moderate.</p><p><b>CONCLUSIONS</b>Tibiotalar and calcaneal-talar joint fusion, osteotomy and fusion for three and four joints could treat severe rigid equinus deformity according to patients' individual and could obtain satisfied clinical effects.</p>

Heterogeneity of Monosymptomatic Resting Tremor in a Prospective Study: Clinical Features, Electrophysiological Test, and Dopamine Transporter Positron Emission Tomography / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The relationship between monosymptomatic resting tremor (mRT) and Parkinson's disease (PD) remains controversial. In this study, we aimed to assess the function of presynaptic dopaminergic neurons in patients with mRT by dopamine transporter positron emission tomography (DAT-PET) and to evaluate the utility of clinical features or electrophysiological studies in differential diagnosis.</p><p><b>METHODS</b>Thirty-three consecutive patients with mRT were enrolled prospectively. The Unified Parkinson's Disease Rating Scale and electromyography were tested before DAT-PET. Striatal asymmetry index (SAI) was calculated, and a normal DAT-PET was defined as a SAI of <15%. Scans without evidence of dopaminergic deficits (SWEDDs) were diagnosed in patients with a subsequent normal DAT-PET and structural magnetic resonance imaging.</p><p><b>RESULTS</b>Twenty-eight mRT patients with a significant reduction in uptake of DAT binding in the striatum were diagnosed with PD, while the remained 5 with a normal DAT-PET scan were SWEDDs. As for UPRDS, the dressing and hygiene score, walking in motor experiences of daily living (Part II) and motor examination (Part III) were significant different between two groups (P < 0.05 and P < 0.01, respectively). Bilateral tremor was more frequent in the SWEDDs group (P < 0.05). The frequency of resting tremor and the amplitude of postural tremor tend to be higher in the SWEDDs group (P = 0.08 and P = 0.05, respectively).</p><p><b>CONCLUSIONS</b>mRT is heterogeneous in presynaptic nigrostriatal dopaminergic degeneration, which can be determined by DAT-PET brain imaging. Clinical and electrophysiological features may provide clues to distinguish PD from SWEDDs.</p>

IFN-γ stimulation enhances immunosuppressive capability of human umbilical cord mesenchymal stem cells / 中国实验血液学杂志

This study was objective to explore the effect of IFN-γ on immunosuppressive capability of mesenchymal stem cells (MSC) derived from umbilical cord. The immunomodulating capability of MSC was changed by stimulating cell surface receptors like Toll-like receptors (TLR). The inhibition of T-lymphocyte proliferation by MSC was tested via cell co-cultures. Further RT-PCR and ELISA were performed to examine the expression changes in gene and protein level. The results showed that the IFN-γ could promote the immunosuppressive effect of umbilical cord derived MSC. IFN-γ-stimulated MSC could suppress the proliferation of T cells more effectively. IFN-γ stimulation up-regulated the expression of immunosuppressive genes like IDO1, COX2, HLA-G, and soluble suppressive proteins such as HLA-G, KYN, IL10, PGE2 of MSC. And the immuno suppression capability of IFN-γ-stimulated MSC was 2-7 folds higher than control in MSC and lymphocyte co-culture tests. It is concluded that IFN-γ can effectively enhance the immunosuppressive capability of MSC.

Prognostic scoring system for locoregional control among the patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy / 癌症

The prognostic value of T category for locoregional control in patients with nasopharyngeal carcinoma (NPC) has decreased with the extensive use of intensity-modulated radiotherapy (IMRT). We aimed to develop a prognostic scoring system (PSS) that incorporated tumor extension and clinical characteristics for locoregional control in NPC patients treated with IMRT. The magnetic resonance imaging scans and medical records of 717 patients with nonmetastatic NPC treated with IMRT at Sun Yat-sen University Cancer Center between January 2003 and January 2008 were reviewed. Age, pathologic classification, primary tumor extension, primary gross tumor volume (GTV-p), T and N categories, and baseline lactate dehydrogenase (LDH) level were analyzed. Hierarchical cluster analysis as well as univariate and multivariate analyses were used to develop the PSS. Independent prognostic factors for locoregional relapse included N2-3 stage, GTV-p ≥26.8 mL, and involvement of one or more structures within cluster 3. We calculated a risk score derived from the regression coefficient of each factor and classified patients into four groups: low risk (score 0), intermediate risk (score >0 and ≤1), high risk (score >1 and ≤2), and extremely high risk (score >2). The 5-year locoregional control rates for these groups were 97.4%, 93.6%, 85.2%, and 78.6%, respectively (P < 0.001). We have developed a PSS that can help identify NPC patients who are at high risk for locoregional relapse and can guide individualized treatments for NPC patients.

Long-term outcome and late toxicities of simultaneous integrated boost-intensity modulated radiotherapy in pediatric and adolescent nasopharyngeal carcinoma / 癌症

The application of simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in pediatric and adolescent nasopharyngeal carcinoma (NPC) is underevaluated. This study aimed to evaluate long-term outcome and late toxicities in pediatric and adolescent NPC after SIB-IMRT combined with chemotherapy. Thirty-four patients (aged 8-20 years) with histologically proven, non-disseminated NPC treated with SIB-IMRT were enrolled in this retrospective study. The disease stage distribution was as follows: stage I, 1 (2.9%); stage III, 14 (41.2%); and stage IV, 19 (55.9%). All patients underwent SIB-IMRT and 30 patients also underwent cisplatin-based chemotherapy. The prescribed dose of IMRT was 64-68 Gy in 29-31 fractions to the nasopharyngeal gross target volume. Within the median follow-up of 52 months (range, 9-111 months), 1 patient (2.9%) experienced local recurrence and 4 (11.8%) developed distant metastasis (to the lung in 3 cases and to multiple organs in 1 case). Four patients (11.8%) died due to recurrence or metastasis. The 5-year locoregional relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 97.1%, 88.2%, 85.3%, and 88.2%, respectively. The most common acute toxicities were grades 3-4 hematologic toxicities and stomatitis. Of the 24 patients who survived for more than 2 years, 16 (66.7%) and 15 (62.5%) developed grades 1-2 xerostomia and ototoxicity, respectively. Two patients (8.3%) developed grade 3 ototoxicity; no grade 4 toxicities were observed. SIB-IMRT combined with chemotherapy achieves excellent long-term locoregional control in pediatric and adolescent NPC, with mild incidence of late toxicities. Distant metastasis is the predominant mode of failure.

Locoregional extension patterns of nasopharyngeal carcinoma and suggestions for clinical target volume delineation / 癌症

Clinical target volume (CTV) delineation is crucial for tumor control and normal tissue protection. This study aimed to define the locoregional extension patterns of nasopharyngeal carcinoma (NPC) and to improve CTV delineation. Magnetic resonance imaging scans of 2366 newly diagnosed NPC patients were reviewed. According to incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were classified into high-risk (>30%), medium-risk (5%-30%), and low-risk (<5%) groups. The lymph node (LN) level was determined according to the Radiation Therapy Oncology Group guidelines, which were further categorized into the upper neck (retropharyngeal region and level II), middle neck (levels III and Va), and lower neck (levels IV and Vb and the supraclavicular fossa). The high-risk anatomic sites were adjacent to the nasopharynx, whereas those at medium-or low-risk were separated from the nasopharynx. If the high-risk anatomic sites were involved, the rates of tumor invasion into the adjacent medium-risk sites increased; if not, the rates were significantly lower (P<0.01). Among the 1920 (81.1%) patients with positive LN, the incidence rates of LN metastasis in the upper, middle, and lower neck were 99.6%, 30.2%, and 7.2%, respectively, and skip metastasis happened in only 1.2% of patients. In the 929 patients who had unilateral upper neck involvement, the rates of contralateral middle neck and lower neck involvement were 1.8% and 0.4%, respectively. Thus, local disease spreads stepwise from proximal sites to distal sites, and LN metastasis spreads from the upper neck to the lower neck. Individualized CTV delineation for NPC may be feasible.