1.Gene mutation profiles and clinicopathological features of patients with non-small cell lung cancer harboring KRAS G12C mutation: a single-center retrospective study.
Lian Ying GUO ; Chan XIANG ; Rui Ying ZHAO ; Sheng Nan CHEN ; Sheng Ji MA ; Yu Chen HAN
Chinese Journal of Pathology 2023;52(2):117-123
Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P=0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P=0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC (P>0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P=0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.
Humans
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Male
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B7-H1 Antigen/genetics*
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Carcinoma, Non-Small-Cell Lung/pathology*
;
China
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Lung Neoplasms/pathology*
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Mutation
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Proto-Oncogene Proteins p21(ras)/genetics*
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Retrospective Studies
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Female
2.Guidelines for management of pediatric acute hyperextension spinal cord injury.
Lian ZENG ; Yu-Long WANG ; Xian-Tao SHEN ; Zhi-Cheng ZHANG ; Gui-Xiong HUANG ; Jamal ALSHORMAN ; Tracy Boakye SEREBOUR ; Charles H TATOR ; Tian-Sheng SUN ; Ying-Ze ZHANG ; Xiao-Dong GUO
Chinese Journal of Traumatology 2023;26(1):2-7
Pediatric acute hyperextension spinal cord injury (SCI) named as PAHSCI by us, is a special type of thoracolumbar SCI without radiographic abnormality and highly related to back-bend in dance training, which has been increasingly reported. At present, it has become the leading cause of SCI in children, and brings a heavy social and economic burden. Both domestic and foreign academic institutions and dance education organizations lack a correct understanding of PAHSCI and relevant standards, specifications or guidelines. In order to provide standardized guidance, the expert team formulated this guideline based on the principles of science and practicability, starting from the diagnosis, differential diagnosis, etiology, admission evaluation, treatment, complications and prevention. This guideline puts forward 23 recommendations for 14 related issues.
Child
;
Humans
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Spinal Cord Injuries/complications*
;
Spinal Cord
3.Changes and clinical significance of erythrocyte lifespan in megaloblastic anemia.
De Peng WU ; Jun BAI ; Song Lin CHU ; Zheng Dong HAO ; Xiao Jia GUO ; Lian Sheng ZHANG ; Li Juan LI
Chinese Journal of Internal Medicine 2023;62(6):688-692
Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B12-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B12-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.
Humans
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Longevity
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Clinical Relevance
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Prospective Studies
;
Erythrocytes
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Anemia, Megaloblastic
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Folic Acid
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Bilirubin
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Vitamins
4.Systematic review and Meta-analysis of Gusongbao preparation in treatment of primary osteoporosis.
Jie-Hang LU ; Zheng-Yan LI ; Guo-Qing DU ; Jun ZHANG ; Yu-Peng WANG ; Jin-Yu SHI ; You-Zhi LIAN ; Fu-Wei PAN ; Zhen-Lin ZHANG ; Hong-Sheng ZHAN
China Journal of Chinese Materia Medica 2023;48(11):3086-3096
This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.
Humans
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Bone Density
;
Low Back Pain
;
Medicine, Chinese Traditional
;
Osteoporosis/drug therapy*
5.Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study.
Xiao-Yun YIN ; Yun-Mei ZHANG ; Ai-Dong SHEN ; Jing-Ping WANG ; Zhe-Xun LIAN ; Yi-Bing SHAO ; Wen-Qi ZHANG ; Shu-Ying ZHANG ; Yang ZHENG ; Kang CHENG ; Biao XU ; Cheng-Xing SHEN ; Rong-Chong HUANG ; Jin-Cheng GUO ; Guo-Sheng FU ; Dong-Kai SHAN ; Dan-Dan LI ; Yun-Dai CHEN
Journal of Geriatric Cardiology 2023;20(4):256-267
OBJECTIVE:
To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS).
METHODS:
In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4.
RESULTS:
Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group.
CONCLUSIONS
In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.
6.Efficacy and safety of anti-PD-1 antibody combined with chemotherapy and anti-angiogenic drugs in advanced melanoma
YANG Yuea ; LIAN Bina△ ; WANG Xuana ; SI Lua ; CHI Zhihonga ; SHENG Xinanb ; MAO Lilia ; CUI Chuanlianga,b ; GUO Juna,b
Chinese Journal of Cancer Biotherapy 2022;29(3):225-229
[摘 要] 目的:探讨抗PD-1单抗联合化疗及抗血管生成药物治疗晚期黑色素瘤的疗效和安全性。方法:收集2020年4月至2021年6月在北京大学肿瘤医院接受抗PD-1单抗联合化疗药物替莫唑胺±顺铂、白蛋白结合型紫杉醇及抗血管生成药物贝伐珠单抗治疗的14例(男6、女8例)不可切除的晚期黑色素瘤患者的临床资料。主要研究终点为无进展生存期(PFS),次要终点为客观有效率(ORR)、疾病控制率(DCR)、总生存期(OS)及安全性数据(CTCAE 5.0标准)。结果:14例晚期黑色素瘤患者均纳入生存分析,中位随访时间为5.50个月(95% CI: 0~13.12个月),中位PFS为7.43个月(95% CI: 3.07~11.79个月),中位OS为13.50个月(95% CI: 5.19~21.81个月),中位起效时间为1.5个月;ORR为28.6%(4例均为部分缓解),DCR为85.7%;不良反应多为1~2级。结论:抗PD-1单抗联合化疗及抗血管生成药物治疗在晚期黑色素患者中显示出初步的有效性及良好的安全性,此可能为晚期黑色素瘤的联合治疗策略提供了新思路。
7. Ancient DNA Damage Analysis of Late Quaternary Mammalian Fossil Samples in Northeast China
Shi-Wen SONG ; Gui-Lian SHENG ; Miao-Xuan DENG ; Xin-Dong HOU ; Gui-Lian SHENG ; Xu-Long LAI ; Jun-Xia YUAN ; Guo-Jiang SUN ; Lin-Ying WANG ; Bo XIAO ; Jia-Ming HU ; Xu-Long LAI
Chinese Journal of Biochemistry and Molecular Biology 2022;38(4):465-473
The advancement of the next generation sequencing (NGS) technology has promoted the development of ancient DNA research. Ancient DNA has made outstanding contributions in various fields such as human origin, animal evolution, etc. How to effectively extract and mine the genetic information from fossil and sub-fossil remains excavated from specific locations is a prerequisite for optimizing their important roles in many fields. In this study, we correlated the two main indicators of DNA damage (terminal base replacement rate, average fragment length) with the possible factors such as the burial time, geological epochs, tissue types, and sequencing library construction methods. The results show that the end base replacement rate of ancient DNA from Northeastern China is positively correlated with the water content of the environment and the ages of the samples. Among samples of different geological epochs, ancient DNA end base replacement rates have significant differences. On the contrary, different tissue types of the remains have no significant effects on the end base replacement rate of ancient DNA. The average fragment size of the molecules has no obvious correlation with the factors mentioned above. The results provide both solid data for investigating the characteristics of ancient DNA from specimens collected in Northeastern China, and valuable information for collecting appropriate samples from different geographical locations and the downstream storage before wet lab procedures after excavation.
8.Minimally invasive treatment of unstable pelvic fractures with blunt head technique of Kirschner wire and 3D-printed external template technigue
Yizhou WAN ; Kaifang CHEN ; Sheng YAO ; Yulong WANG ; Lian ZENG ; Tingfang SUN ; Xiaodong GUO
Chinese Journal of Orthopaedic Trauma 2022;24(12):1024-1029
Objective:To explore the safety and efficacy of the minimally invasive treatment of unstable pelvic fractures with the blunt head technique of Kirschner wire and 3D-printed external template technique.Methods:A retrospective study was conducted of the clinical data of 21 patients with unstable pelvic fracture who had undergone minimally invasive treatment at Department of Orthopaedics, Union Hospital from May 2016 to July 2018 using 3D-printed external templates and the blunt head technique of Kirschner wire. There were 7 males and 14 females with an age of 43.6 years (from 19 to 65 years). According to the Tile classification, there were 3 cases of B1, 7 ones of B2, 6 ones of C1 and 5 ones of C2. The intraoperative fluoroscopy, operation time, postoperative fracture reduction and functional recovery of the pelvis at the last follow-up were recorded.Results:The 21 patients were followed up for an average of 16.3 months (from 12 to 24 months). A total of 33 wires were inserted in the 21 patients, including 15 S 1 ones and 18 S 2 ones. The intraoperative fluoroscopy ranged from 13 to 27 times, averaging 21.8 times. The operation time ranged from 65 to 130 min, averaging 88.6 min. The anterior subcutaneous internal fixation was used to fix the anterior ring in 9 patients. No vascular injury occurred during the operation. By the Matta criteria, the postoperative fracture reduction was assessed as excellent in 14 cases, good in 5, and fair in 2, giving an excellent to good rate of 90.5% (19/21). By the Majeed scoring system, the pelvic function at the last follow-up was assessed as excellent in 10 cases, good in 8, and fair in 3, giving an excellent to good rate of 85.7% (18/21). Lateral femoral cutaneous nerve injury occurred in 2 patients but was recovered by the 3-month follow-up. No other complications were follwed up. Conclusion:The minimally invasive treatment of unstable pelvic fractures with the blunt head technique of Kirschner wire assissted by 3D-printed external templates is safe and effective, showing advatages of reduced fluoroscopic frequency and operation time.
9.Treatment of acetabular both column fractures with integrated acetabular quadrilateral surface buttress plate
Sheng YAO ; Kaifang CHEN ; Yizhou WAN ; Yulong WANG ; Lian ZENG ; Fengzhao ZHU ; Jia LIU ; Liang YANG ; Xiaodong GUO
Chinese Journal of Orthopaedics 2021;41(15):1010-1017
Objective:To investigate the advantages and disadvantages and clinical effects of integrated acetabular quadrilateral surface buttress plate in the treatment of acetabular both column fractures.Methods:From September 2017 to March 2019, 14 patients with acetabular both column fractures were treated with integrated quadrilateral acetabular buttress plate and were followed up. The clinical data were retrospectively analyzed. There were 10 males and 4 females with an average age of 53.2 years (range, 26-75 years). Fracture classification were both column fractures according to the Letournel-Judet classification system, including 11 cases of combined posterior wall without posterior dislocation. The time from injury to operation was 8-19 days, with an average of 10.3 days. All operations were performed with a supra-ilioinguinal approach. After satisfactory reduction, the integrated acetabular quadrilateral surface buttress plate was used to fix the anterior and posterior column and quadrilateral fractures at the same time. After operation, Matta criteria was used to evaluate the quality of fracture reduction on postoperative images, and modified Merle d'Aubigné-Postel score to evaluate hip joint function.Results:The average operation time was 180 min (range, 120-320 min), and the intraoperative average blood loss was 980 ml (range, 700-1 600 ml). Operations were performed successfully with none intraoperative reshaping conducted, and the plate could fit into the bone surface well. All 14 patients were followed up with an average of 15.6 months (range, 9-20 months). During the follow-up, all fractures healed with an average of 3 months (range, 2.5-5 months). The reduction quality evaluated by the Matta criteria were 7 anatomical, 5 satisfactory, and 2 unsatisfactory, with an excellent and good rate of 85.7% (12/14). The hip joint function at the last follow-up was in accordance with the modified Merle d'Aubigné-Postel score was 12-18 points, with an average of 16.9 points, of which 8 excellent, 4 good, and 2 fair. The excellent and good function rate was 85.7% (12/14). During the operation, 1 patient had a rupture of about 1 cm of the peritoneum during the separation of the spermatic cord, which was immediately sutured and repaired. One patient had obturator nerve paralysis after the operation, without special treatment, and the paralysis symptoms were relieved during the 6th-month follow-up. There were no other operation-related complications.Conclusion:For both-column fractures characterized by central dislocation of the femoral head, the integrated acetabular quadrilateral buttress plate can simultaneously fix the anterior and posterior columns and quadrilateral surface at the same time. Satisfactory reduction and functional outcomes could be achieved by the novel plates.
10.The treatment of acetabular posterior wall/column fracture with the novel integrative anatomical plate
Yizhou WAN ; Sheng YAO ; Kaifang CHEN ; Yulong WANG ; Lian ZENG ; Guixiong HUANG ; Xiaodong GUO
Chinese Journal of Orthopaedics 2021;41(19):1419-1425
Objective:To explore the feasibility, safety and clinical efficacy of using the self-developed acetabular posterior wall and column integrative anatomical plate to treat various types of posterior wall/column fractures.Methods:Between January 2016 and January 2019, 21 patients involving acetabular posterior wall and/or column were treated with the novel acetabular posterior wall and column integrative plate, the data were collected and retrospectively analyzed. There were 11 males and 10 females, with an average of 48 years old (range, 18-65 years old). According to the classification of AO/OTA, there were 6 simple fractures, 9 comminuted fractures, and 6 associated with joint surface compression of posterior wall; and there were 16 simple acetabular posterior wall fractures and 5 cases associated with acetabular posterior column fractures. Before operation, the CT data of each patient was collected and imported into Mimics software to reconstruct and print a 3D model of pelvis and injured and mirrored side to simulate operation. All patients were treated with a single Kocher-Langenbeck approach for posterior acetabular fractures, and fixed with the novel integrated anatomical plate after satisfactory reduction was achieved. Matta score was used to evaluate the quality of fracture reduction, and the modified Merle D'Aubigné-Postel score was adopted to evaluate functional recovery of hip joint.Results:21 patients involved in this study, the average time of plate insertion after successful reduction was 20 min (range, 15-30 min); the mean time of operation was 180 min (range, 90-300 min); the intraoperative mean bleeding volume was 700 ml (range, 300-1 500 ml). All the incisions healed by level 1 classification, and no incisions infection and sciatic nerve injury occurred. The patients included in the study have been followed up for at least one year and the imaging data was intact, the mean follow-up time was 19 month (range, 12-26 month). The fracture reduction was evaluated according to the Matta score: 16 cases were anatomical reduction, 3 cases were satisfactory reduction, 2 cases were unsatisfactory reduction, the satisfactory rate of reduction was 90.5% (19/21); the modified Merle D'Aubigné-Postel score at 3 month was 13.0±2.2 (range, 9-16), 6 month was 15.8±2.4 (range, 10-18) and last follow up was 17.0±1.8 (range, 13-18), respectively; the difference was statistically significant ( F=15.38, P < 0.001). At the last follow-up, 15 cases were excellent, 3 cases were good and 3 cases were fair, the total excellent and good rate was 85.7% (18/21). One case developed symptoms of sciatic nerve injury after operation, but the symptoms resolved after treating with neurotrophic drug by 6 months. 2 cases developed arthritis related pain after operation, receiving symptomatic treatment with oral painkillers. During the follow-up period, no complications such as plate broken and screw loosen occurred. Conclusion:The use of an integrative anatomical plate for treating posterior wall/column fractures of acetabulum achieved satisfactory fixation and postoperative functional recovery.

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