靶向维生素D受体的miRNA的筛选及其对继发性甲状旁腺功能亢进患者甲状旁腺激素分泌的影响

目的探讨靶向维生素D受体（VDR）基因的miRNA及其对继发性甲状旁腺功能亢进甲状旁腺激素（PTH）分泌的影响。方法用胶原酶消化法提取、分离和培养出继发性甲状旁腺功能亢进的甲状旁腺组织的原代细胞；运用生物信息学方法及全转录组测序的方法筛选得到靶向VDR的miRNA，双荧光素酶报告基因实验验证筛选出的miRNA与VDR的靶向关系；qRT-PCR及Western blotting检测过表达或抑制miRNA后的对VDR mRNA水平及蛋白水平和对PTH分泌的影响；qRT-PCR和免疫组织化学分别验证部分miRNA、VDR mRNA和蛋白水平的表达差异。结果成功培养得到甲状旁腺原代细胞；筛选并验证了hsamiR-149-5p、hsa-miR-221-5p、hsa-miR-222-3p、hsa-miR-29a-5p、hsa-miR-301a-5p、hsa-miR-873-5p、hsa-miR-93-3p均与VDR存在靶向关系；筛选并验证的7个miR中，过表达hsa-miR-149-5p、hsa-miR-301a-5p PTH分泌增加。hsa-miR-149-5p在继发性甲状旁腺功能亢进中高表达（P=0.046），VDR mRNA（P=0.0267）和蛋白水平表达均下降。结论hsa-miR-149-5p、hsa-miR-301a-5p可能通过下调VDR基因的表达促进继发性甲状旁腺功能亢进患者PTH的分泌。     

造血干细胞移植后输尿管狭窄1例

Ureteral stenosis is a comparatively rare complication following hematopoietic stem cell transplantation (HSCT). The etiology is still unclear and most believe that this may be due to the reactivation of BK virus in a state of immunodeficiency. In the later stages of ureteral stenosis with scarring, invasive interventions must be taken to relieve the hydronephrosis. Common treatments, such as D-J stent placement and permanent nephrostomy may not only entail the risk of infection, but also seriously affect the quality of life. Few cases of surgical intervention have been reported. In this article, a 25-year-old female was admitted to Peking University First Hospital suffering from recurrent flank pain. Seven years before, she developed hemorrhagic cystitis and bilateral urethritis 40 days after allogeneic HSCT. After continuous bladder irrigation and antiviral therapy, the left-sided hydronephrosis gradually alleviated while the right-sided one did not improve. D-J stents were used for urine drainage for 7 years before percuta-neous nephrostomy. Preoperative antegrade pyelography revealed significant hydronephrosis in the right kidney with long stricture of proximal-middle ureter. After comprehensive decision, she underwent ileal ureter replacement. The operation was successful. The segmental lesion was dissected and the scar tissue was removed. A 25 cm intestinal tube was isolated to connect the pelvis and bladder. An anti-reflux nipple was created at the distal end of ileal ureter to prevent the potential infection. The blood loss was minimal. After surgery, the drainage tube was removed in 2 weeks, the nephrostomy tube and the D-J stent was removed in 3 months. Follow-up mainly included clinical assessment, serologic testing, renal ultrasonography, blood gas analysis and radiological examination. During the follow-up of 6 years, she was symptom-free and no postoperative complications occurred. The serum creatinine level was stable. No hydronephrosis was observed under ultrasonography. Obvious peristaltic waves and ureteral jets of the ileal ureter was confirmed on cine magnetic resonance urography. To sum up, ureteral stenosis after HSCT is relatively rare. Obstruction caused by scarring is usually irreversible and surgical intervention should be designed according to the location and length of the lesion. Ileal ureter replacement can be a safe, feasible and effective method to solve this kind of complex stricture.     

继发性甲状旁腺功能亢进症来源的甲状旁腺原代细胞的培养及鉴定

目的分离、培养及鉴定继发性甲状旁腺功能亢进症患者来源甲状旁腺。方法采用胶原酶消化法提取10例继发性甲状旁腺功能亢进症的甲状旁腺原代细胞进行体外培养，通过显微摄像、细胞计数研究其形态学变化及生长特性，用细胞免疫荧光、qRT-PCR及Western blot检测原代及传代甲状旁腺细胞甲状旁腺素（PTH）、钙敏感受体（CaSR）和神经胶质细胞缺失因子2（GCM2）mRNA及蛋白的表达情况，对所得细胞进行分析鉴定。结果本研究成功提取甲状旁腺原代细胞，其细胞PTH免疫荧光结果为阳性，细胞增长曲线显示甲状旁腺细胞体外分散培养的群体倍增时间约为71.61 h。P2代细胞分泌PTH较P0、P1代细胞减少（P < 0.001）。P1代细胞和P0代细胞间PTH（P=0.572）和GCM2（P=0.892）的mRNA表达差异无统计学意义，PTH（P=0.572）和GCM2（P=0.892）的蛋白表达差异也无统计学意义。但P1代细胞的CaSR mRNA（P=0.017）和蛋白表达（P=0.006）均较P0代甲状旁腺细胞减少。结论采用胶原酶消化法培养的甲状旁腺细胞一定程度上具有与在体细胞相似的细胞生物学特性。     

135例肾移植受者移植物丢失的原因分析

目的探讨肾移植术后受者移植肾丢失的原因。方法回顾性分析2002年1月1日~2022年1月1日在中国人民解放军总医院第八医学中心肾移植术后移植物发生丢失的135例受者临床资料。结果受者移植肾丢失135例，移植肾丢失原因包括排斥反应70例（51.8%）、受者带功能死亡37例（27.4%）、外科并发症12例（8.9%）、药物毒性4例（3.0%）、耐碳青霉烯肺炎克雷伯菌感染4例（3.0%）、多瘤病毒相关性肾病3例（2.2%）、原发性无功能肾2例（1.5%）、原发病复发2例（1.5%）、肾前性急性肾衰1例（0.7%）。结论肾移植术后受者移植物丢失原因主要原因是排斥反应，次要原因是受者带功能死亡，其他原因少见。     

肾上腺海绵状血管瘤1例及文献回顾

A 57-year-old male patient was referred to our department with complaints of his right adrenal gland occupancy and hypertension about 6 months. When admitted to the hospital, the blood pressure was about 160/100 mmHg, and the heart rate was 110 beats/min. He was no obvious obesity, acne, abnormal mood, without weakness of limbs, acral numbness, palpitation and headache. He presented with type 2 diabetes for more than 3 years, with oral administration of metformin enteric coated tablets and subcutaneous injection of insulin glargine to control blood glucose, and satisfied with blood glucose control. Enhanced CT showed that: the right adrenal gland showed a kind of oval isodense, slightly hypodense shadow, the edge was clear, lobular change, the size was about 5.8 cm×5.4 cm, uneven density, there were nodular and strip calcification, round lipid containing area and strip low density area, and the CT value of solid part was about 34 HU. Enhanced scan showed heterogeneous nodular enhancement in the solid part of the right adrenal gland, nodular enhancement could be seen inside. The CT values of solid part in arterial phase, venous phase and delayed phase were 45 HU, 50 HU and 81 HU, respectively. Considering from the right adrenal gland, cortical cancer was more likely. No obvious abnormality was found in his endocrine examination. After adequate preoperative preparation, retroperitoneal laparoscopic adrenalectomy was performed under general anesthesia. During the operation, the 6 cm adrenal tumor was closely related to the inferior vena cava and liver, and after careful separation, the tumor was completely removed and normal adrenal tissue was preserved. The operation lasted 180 min and the blood loss was 100 mL, and the blood pressure was stable during and after the operation. There was no obvious complication. The results of pathological examinations were as follows: the size of the tumor was 7.5 cm×6.0 cm×3.5 cm, soft, with intact capsule and grayish-red cystic in section. Pathological diagnosis: (right adrenal gland) cavernous hemangioma, secondary intravascular thrombosis, old hemorrhagic infarction with calcification and ossification. After 6 months of observation, no obvious complications and tumor recurrence were found. In summary, cavernous hemangioma of adrenal gland is a rare histopathological change. Its essence is a malformed vascular mass. Blood retention is the cause of thrombosis and calcification in malformed vessels. The imaging findings were inhomogeneous enhancement of soft tissue masses, and the adrenal function examination showed no obvious abnormalities. Retroperitoneal laparoscopic surgery is feasible after adequate preoperative preparation. It is difficult to diagnose the disease preoperatively and needs to be confirmed by postoperative pathology.     

微波消融术前甲状腺良性结节的风险分级有临床价值

目的探讨甲状腺良性结节微波消融术前的风险分级方法及临床意义。方法根据甲状腺结节的毗邻关系, 术前将结节消融风险分为低风险、中风险、高风险和极高风险4级。记录术后严重并发症发生率及结节残留发生率。结果527例甲状腺结节患者微波消融术后低、中、高和极高风险组的严重并发症的发生率为0%、0.88%、2.41%和6.78%, 各组差异均无统计学意义 (P > 0.05)。术后低、中、高和极高风险组的结节残留发生率分别为1.59%、6.14%、14.43%和71.19%, 其中低风险与中风险组差异无统计学意义(P > 0.05);但低风险、中风险组与高风险、极高风险组差异有统计学意义(P < 0.001)。结论甲状腺结节术前风险分级有助于术中严重并发症的预防及术后结节残留发生率的预估。     

肾移植术后双侧乳头状肾癌1例

With the continuous development of kidney transplantation technique, the survival time after kidney transplantation is gradually prolonged. Thus, the malignant tumor has been the important influencing factor on the long-term survival for kidney transplantation patients. Renal cell carcinoma is a relatively common tumor after kidney transplantation. Besides, clear cell renal cell carcinoma and papillary renal cell carcinoma are the relatively common pathological types for renal cell carcinoma following kidney transplantation. However, bilateral renal cell carcinoma following kidney transplantation is comparatively rare. In this article, we presented a case of bilateral papillary renal cell carcinoma, which occurred after kidney transplantation. And the diagnosis and treatment were introduced in detail. The patient was 37 years old, and he underwent kidney transplantation 13 years ago in our hospital, because of kidney failure. After kidney transplantation, he had regular medical check-up every year. In this year, his urological ultrasound results indicated bilateral renal tumors. And then, he received abdominal and pelvic computed tomography, and the result also showed bilateral renal tumors, which were likely to be malignant tumors. After adequate consultation, the patient chose surgical treatment. The patient received long-term immunosuppressive therapy, because of kidney transplantation. Considering this, the surgeon decided to choose a staging surgical treatment, in order to reduce the bad influence of one-stage surgery. Then, the patient first underwent retroperitoneal laparoscopic radical nephrectomy for right renal tumor in our hospital, and he had no complications after operation. The pathological results showed papillary renal cell carcinoma. He was discharged successfully. He underwent retroperitoneal laparoscopic radical nephrectomy for left renal tumor in our hospital one month later, and he had no complications after operation. The pathological results also showed papillary renal cell carcinoma. He was discharged successfully two days after surgery. In the 3-month follow-up, the patient was recovering well. To sum up, the incidence of bilateral renal cell carcinoma following kidney transplantation is relatively rare, and bilateral radical nephrectomy is effective and safe treatment. Above all, it is the patient''s condition that determines the choice of staging surgery or simultaneous surgery.     

中国老年人群促甲状腺激素水平的多中心调查

目的调查中国表观健康老年人群血清促甲状腺激素（TSH）水平及其变化特征，对比罗氏电化学发光免疫分析仪和新产业全自动化学发光免疫分析仪检测TSH水平的差异。方法收集中国具有地域代表性的10个中心共5451例表观健康老年人（> 60岁）一般临床资料及冻存空腹血清样本，通过罗氏电化学发光免疫分析仪和新产业全自动化学发光免疫分析仪检测TSH等甲状腺功能指标。使用中位数（P_2.5，P_97.5）表示老年人群TSH水平。分析不同地域、性别、年龄组（组距为5）TSH水平差异，探索各因素对TSH水平的影响。结果罗氏电化学发光法和新产业全自动化学发光法调查TSH参考区间分别为0.42~9.47 mU/L；0.36~7.98 mU/L，两种方法检测TSH结果有差异（P < 0.001）。2个西部地区中心TSH水平显著高于其他中心（P < 0.05）；老年女性TSH水平不随年龄增长，而老年男性TSH水平随年龄增长有增长趋势；60~75岁女性TSH水平普遍高于男性， > 75岁男性女性TSH水平无显著差异。结论TSH水平受地区、性别、年龄因素影响，但老年人群无需再根据地区、性别、年龄再分组建立参考区间。TSH结果解读应注意不同检测方法之间的差异。     

新型大气压冷等离子体射流处理对牙本质胶原纤维交联化的影响

目的研究新型大气压射频辉光放电(radio-frequency atmospheric-pressure glow discharge，RF-APGD)等离子体处理对牙本质胶原纤维交联化的影响。方法(1) 收集20颗新鲜拔除的、完整的第三磨牙，采用低速水冷精密切割机制备平行于牙合面的中层牙本质片，厚度为(1.5±0.1) mm，浸泡于10%(质量分数)H₃PO₄溶液中16 h获得全脱矿牙本质胶原纤维。将20个牙本质胶原纤维片随机分为5组，对照组无处理，4个实验组采用气体温度为4 ℃的等离子体处理不同时间(20 s、30 s、40 s、50 s)。采用衰减全反射傅里叶变换红外光谱仪测定牙本质胶原纤维结构及交联度，采用扫描电镜观察牙本质胶原纤维表面形貌，采用透射电镜观察牙本质胶原纤维微观结构。(2)收集完整第三磨牙40颗，制备精细牙本质粉5 g，10%H₃PO₄溶液中完全脱矿，将牙本质胶原纤维粉平均分为5组。对照组无处理，实验组分别采用等离子体处理20 s、30 s、40 s、50 s，采用茚三酮比色法测定各组交联度。(3)收集40颗完整第三磨牙，制备中层牙本质条。将牙本质胶原纤维条随机均分为5组，对照组无处理，实验组采用等离子体处理牙本质胶原纤维条各个轴面20 s、30 s、40 s、50 s，采用万能力学机测定牙本质极限拉伸强度。结果(1) 扫描电镜观察脱矿牙本质表面形貌显示，等离子体处理20 s、30 s及40 s，脱矿牙本质表面胶原纤维网状结构均能维持蓬松；等离子体处理50 s会出现部分微结构的破坏；透射电镜结果显示等离子体处理20 s、30 s及40 s后，纤维结构蓬松，可见天然Ⅰ型胶原纤维典型的周期性横纹；红外光谱结果显示，等离子体处理后，胶原纤维的二级构象与对照组一致，且处理30 s及40 s后酰胺带强度明显增加。(2)茚三酮交联度测试结果显示等离子体处理30 s组及40 s组交联度最高，差异有统计学意义(P＜0.05)。(3)牙本质极限拉伸强度结果显示，对照组为(1.67±0.24) MPa，等离子体处理20 s、30 s、40 s、50 s组分别为(4.21±0.15) MPa、(7.06±0.30) MPa、(7.32±0.27) MPa、(6.87±0.17) MPa，与对照组差异有统计学意义(P＜0.05)。结论新型RF-APGD等离子体处理可以促进脱矿牙本质胶原纤维交联，同时明显增强了牙本质胶原纤维的机械性能。     

褪黑素通过激活自噬抑制MDA-MB-231乳腺癌细胞的生长和转移

目的探讨褪黑素对乳腺癌细胞MDA-MB-231生长和转移的作用及其机制。方法将MDA-MB-231细胞设置对照组以及1、3、5 mmol/L褪黑素处理组，Western blot检测自噬对细胞生长、转移的影响时，添加3-甲基腺嘌呤（3-MA）组、3-MA联合褪黑素组。使用不同浓度褪黑素处理MDA-MB-231乳腺癌细胞24、48 h，并加入0.1%无水乙醇的细胞作为对照，CCK-8法检测细胞增殖活性确定最佳处理浓度和时间，筛选出3 mmol/L褪黑素用于后续实验。集落形成实验及划痕实验检测不同浓度褪黑素对乳腺癌细胞集落形成能力和迁移能力的影响；流式细胞术、免疫荧光检测3 mmol/L褪黑素对MDA-MB-231细胞凋亡率和自噬蛋白阳性着色情况；Western blot检测自噬相关蛋白LC3、P62、Beclin1，凋亡相关蛋白Bcl2、Bax，上皮-间质转化（EMT）相关蛋白E-cadherin、Snai1的水平。结果CCK-8结果显示，与对照组相比，褪黑素呈浓度及时间依赖性抑制乳腺癌细胞的增殖（P < 0.05）；集落形成实验显示，3个浓度褪黑素处理组的集落数低于对照组；褪黑素作用24 h后明显抑制乳腺癌细胞划痕愈合速度（P < 0.01），并诱导细胞凋亡率增加（P < 0.01）；且与对照组相比，褪黑素组的促凋亡蛋白Bax表达增加（P < 0.05），抗凋亡蛋白Bcl2表达下调（P < 0.05），Bcl2/Bax的比值逐渐减低（P < 0.01）；转录因子Snail减少，上皮细胞标志蛋白E-cadherin增加；单独使用褪黑素能够诱导细胞内自噬标记蛋白LC3-ΙΙ/LC3-Ι、Beclin1表达增加，P62表达减少（P < 0.05）以及Beclin1蛋白阳性着色增强，P62蛋白阳性着色减弱；3-MA+褪黑素组中自噬相关蛋白Beclin1（P < 0.001）、LC3-ΙΙ/LC3-（ΙP < 0.05）以及凋亡蛋白Bax（P < 0.01）、上皮细胞标志蛋白E-cadherin（P < 0.001）明显低于褪黑素组，抗凋亡蛋白Bcl2（P < 0.05）、转录因子Snail以及Bcl2/Bax的比值（P < 0.01）高于褪黑素组。结论褪黑素可通过诱导MDA-MB-231乳腺癌细胞发生自噬，抑制乳腺癌细胞增殖、转移并促进其凋亡，而减少自噬，可减弱褪黑素对乳腺癌细胞生长和转移的抑制作用。     

局部注射环孢素A对非肥胖糖尿病小鼠下颌下腺分泌功能及炎症的影响

目的探讨非肥胖糖尿病(non-obese diabetic, NOD)小鼠下颌下腺局部注射环孢素A(cyclosporine A, CsA)对腺体唾液分泌功能及炎症的影响。方法选用21只14周龄和18只21周龄雌性NOD小鼠，随机平均分为低剂量组、高剂量组和对照组。NOD小鼠下颌下腺局部注射CsA 1周后，检测刺激性唾液流率；取下颌下腺标本，制作石蜡切片，用苏木精-伊红(hematoxylin-eosin staining，HE)染色，显微镜下观察腺体淋巴细胞浸润程度；用徕卡图像分析系统计数淋巴细胞浸润灶的数量，计算灶性指数和淋巴细胞浸润灶的面积比；用实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction, qRT-PCR)检测下颌下腺中肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)、干扰素-γ(interferon-γ, IFN-γ)、白介素-4(interleukin-4, IL-4)、IL-13、IL-17F、IL22和IL-23a等炎症细胞因子的表达；用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, TUNEL)检测下颌下腺凋亡细胞；用全自动生化分析仪测量血清肌酐(serum creatinine，Scr)、尿素氮(blood urea nitrogen, BUN)、尿酸(uric acid, UA)、丙氨酸氨基转移酶(alanine aminotransferase，ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase，AST)、碱性磷酸酶(alkaline phosphatase, ALP)、白蛋白(albumin, ALB)和γ-谷氨酰基转移酶(γ-glutamyl transferase，GGT)，评估肝肾功能。结果下颌下腺局部注射CsA后，14周龄和21周龄NOD小鼠的刺激性唾液流率较同龄对照组明显增加(P < 0.01或P < 0.05)；14周龄低剂量组NOD小鼠下颌下腺淋巴细胞浸润灶的灶性指数和面积比较同龄对照组显著减少(P < 0.01)；低剂量和高剂量组减轻炎症反应和改善唾液分泌功能的作用相似；下颌下腺整体炎症细胞因子表达水平无明显降低；低剂量和高剂量组下颌下腺凋亡细胞数和对照组相比有减少趋势，但差异无统计学意义；局部注射CsA对NOD小鼠肝肾功能无影响。结论局部应用CsA可减轻NOD小鼠的下颌下腺淋巴细胞浸润，并改善唾液分泌功能。     

多中心网状组织细胞增生症1例

A 65-year-old woman developed erythema, papules and nodules over the body. Some nodules of her auricles and hands like string beads. Besides, she suffered from symmetrical swelling and pain of multiple joints, morning stiffness with deformity of joints; She had elevated erythrocyte sedimentation rate and C reactive protein levels; Her rheumatoid factor and antinuclear antibody were positive; Joints destruction was found with X-ray imaging; Skin pathology showed Dermal infiltrate of abundant histiocytes, part of them with a ground-glass appearance; A CD68 immunohistochemical stain was positive and the cells were negative for S100, CD1a. These findings were diagnostic evidences of multicentric reticulohistiocytosis (MRH). The patient received high-dose of glucocorticoids combinated with immunosuppressive agents, and achieved a satisfactory effect. MRH was a rare multisystem disease characterized by papulonodular mucocutaneous and destructive arthritis, and its pathogeny was not yet completely understood. The typical lesions of MRH were hard papules or nodules that usually occured on the hands, face and arms. Classic coral bead appearance from periungual cutaneous nodules that were characteristic of MRH. MRH was an inflammatory joint disease, affecting almost all the appendicular joints and characterized by joint multiple, symmetrical, destructive, progressive disability. Joints destruction of the distal interphalangeal joints was a unique feature of MRH. In addition to skin and joints, it could also involve other systems. There were no diagnostic laboratory markers for MRH. Laboratory examinations had often been found to be non-specific. Imageological examination mainly showed bone and joint destruction. Skin biopsy was the best test to diagnose MRH, the typical histopathological findings included an infiltrate with histiocytes and multinucleated giant cells with a ground-glass appearing in eosinophilic cytoplasm, and the immunohistochemical stain was positive for CD68. The diagnosis was typically made based on the clinical presentation, supportive radiographic findings and skin biopsy. MRH was easily possible to mistake for other more common autoimmune conditions, such as rheumatoid arthritis, psoriatic arthritis, osteoarthritis, and dermatomyositis, but the distinctive clinical, radiographic, and histologic features could aid in differentiating these diseases. MRH could mimic other rheumatic diseases, besides, it could also coexist with cancer or other autoimmune disorders. There was no standardized treatment for MRH. However, Nonsteroidal anti-inflammatory drugs, glucocorticoid, Immunosuppressant, biologic medications, and bisphosphonates had been used with varying degrees of curative effect. Treatment with glucocorticoid combined with immunosuppressants were effective for rash and arthritis, early use of them should be strongly considered, and refractory cases could be treated with biological agents. By reporting a MRH case and reviewing literature, this paper aims to help the clinicians improve the understanding of this rare disease, and suggests that when one diagnosis cannot explain the whole picture of the disease, and further evidence should be sought to confirm the diagnosis.     

头颈部游离组织瓣移植术后预防性气管切开的临床分析

目的探讨头颈部游离组织瓣移植患者术后行预防性气管切开的影响因素。方法选择2015—2016年北京大学口腔医院口腔颌面外科同一手术团队连续完成的533例头颈部游离组织瓣移植术患者的病例资料进行回顾性分析, 患者平均年龄(49.3±16.6)岁, 其中321例患者行预防性气管切开术, 占全部患者的60.2%。记录患者基本信息、手术因素、治疗史、患有共病、个人史及术后并发症发生情况。结果手术伴有舌、口底、口咽部、双侧下颌骨缺损, 行单侧及双侧颈淋巴清扫术, 既往有放疗史、吸烟史者, 以及应用较臃肿软组织皮瓣的患者, 术后气道梗阻风险较大, 更倾向于行预防性气管切开。有1例未行预防性气管切开术的患者术后出现气道梗阻行紧急气管切开。预防性气管切开术患者中, 8.39%出现气管切开相关并发症, 以肺部感染、切口出血为主。结论并非所有行头颈部游离组织瓣移植修复的患者均需行预防性气管切开术, 头颈部游离组织瓣移植术患者是否行预防性气管切开术需根据具体情况综合判断, 以保证患者的术后气道安全。     

影响全膝关节置换术患者术前预期的患者因素

目的术前预期会影响关节置换术后患者的主观满意度及客观功能，调查患者对全膝关节置换术的预期情况，并分析其影响因素。方法收集108例单侧全膝关节置换术患者的人口学资料，以及术前的美国特种外科医院(Hospital for Special Surgery，HSS) 膝关节置换手术预期量表评分、30秒座椅站立测试、40米快速步行测试、12级爬楼梯测试、3米起立行走测试、6分钟步行测试、美国西部Ontario和McMaster大学(the Western Ontario and McMaster Universities，WOMAC)骨关节炎指数评分、膝关节学会评分(Knee Society score，KSS)、健康调查简表(the MOS 36-item short-from health survey, SF-36)评分、视觉模拟评分(visual analogue scale, VAS)以及连续7天的每日步数。对各数据的观察值进行描述性报告，应用Pearson相关分析评估各参数间的相关性并进行多因素线性回归分析。结果患者的平均术前预期评分为58.98±5.44，其与患者的12级爬楼梯测试、3米起立行走测试、6分钟步行测试、KSS功能评分、SF-36的精神健康评分有弱相关性(相关系数0.1~0.3)，与患者的每日平均步数，30秒座椅站立测试，40米快速步行测试，KSS膝关节评分，WOMAC及其疼痛、僵直、功能三个评分，SF-36的生理功能、生理职能、躯体疼痛、活力及躯体健康评分有中度相关性(相关系数0.3~0.6)。多因素线性回归分析显示，仅有30秒座椅站立测试和SF-36量表中的生理职能、躯体疼痛及活力与患者对手术效果的预期评分有相关性(P < 0.05)。结论术前疼痛更重、躯体功能更差、整体健康状况更低下的患者更迫切希望得到改善，医生要在术前与预期不现实的患者充分沟通。     

系统性红斑狼疮患者血清白细胞介素-2受体α水平及其临床意义

目的探究系统性红斑狼疮(systemic lupus erythematosus，SLE)患者血清中白细胞介素-2受体α(interleukin-2 receptor α，IL-2Rα)水平在临床中的意义。方法收集2019年1月至2020年12月就诊于北京大学人民医院的107例SLE患者病历资料，依据SLE疾病活动度指数(SLE disease activity index 2000，SLEDAI-2K)评估患者的病情活动情况，并选取年龄、性别分别匹配的39例健康人作为健康对照。采用酶联免疫吸附法测定SLE患者组和健康对照组的血清IL-2Rα水平，比较其差异并分析SLE患者IL-2Rα水平与临床指标及实验室指标的相关性。采用t检验或Mann-Whitney U检验、χ²检验和Spearman秩相关性分析进行统计学分析。结果SLE患者血清IL-2Rα水平[830.82(104.2~8 940.48) ng/L]较健康对照组[505.1(78.65~1 711.52) ng/L]明显升高(P < 0.001)。相关性分析显示，血清IL-2Rα水平与SLEDAI-2K评分及抗核小体抗体滴度呈正相关(r=0.357，P < 0.001;r=0.25，P=0.027)。107例SLE患者中36例(33.6%)合并狼疮性肾炎，合并狼疮性肾炎的患者血清IL-2Rα水平[1 102.14(126.52~8 940.48) ng/L]较未合并狼疮性肾炎患者[743.89(104.19~4 872.06) ng/L]明显升高(P=0.032)。高IL-2Rα水平组合并狼疮性肾炎者(40.8%)较低水平组(19.4%)明显升高(P=0.031)，高IL-2Rα水平组SLEDAI-2K评分更高[10 (3~21) vs. 7 (3~16)，P=0.001]。SLE患者常规治疗12周后血清IL-2Rα水平[1 119.1(372.25~2 608.86) ng/L]随病情改善较基线时[1 556.73 (373.08~8 940.48) ng/L]明显下降(P=0.042)。结论血清IL-2Rα可作为SLE病情活动评估指标，与肾脏受累有一定相关性。     

临床T1期肾细胞癌肾窦侵犯的危险因素

目的总结临床T1(cT1)期肾细胞癌的临床影像学特点，探究影响cT1期肾细胞癌患者发生肾窦侵犯的危险因素。方法回顾性分析2016年1月至2019年8月于北京大学第三医院泌尿外科住院行肾部分切除术或根治性肾切除术，术前诊断为cT1期肾细胞癌的患者，收集患者的临床、影像学和病理学资料。采用卡方检验、Mann-Whitney U检验、多因素Logistic回归，对cT1期肾细胞癌发生肾窦侵犯的相关危险因素进行分析。结果共纳入507例患者，其中男性354例(69.8%)，女性153例(30.2%)，中位年龄59岁，中位体重指数25.5 kg/m²。术前有肉眼血尿者18例(3.6%)，中位肿瘤直径3.5 cm。cT1a期322例(63.5%)，cT1b期185例(36.5%)，中位R.E.N.A.L.评分为8分。肿瘤边界规则者359例(70.8%)，肿瘤边界不规则者148例(29.2%)。所有患者均行手术治疗，包括186例(36.7%)肾部分切除术和321例(63.3%)根治性肾切除术。术后病理提示肾窦侵犯75例(14.8%)，其中cT1a期侵犯肾窦18例，占cT1a期总数的5.6%;cT1b期侵犯肾窦57例，占cT1b期总数的30.8%。单因素分析发现，年龄(P=0.02)、R.E.N.A.L.评分(P < 0.001)、肿瘤边界状态(P < 0.001)是cT1期肾细胞癌发生肾窦侵犯的相关危险因素。多因素Logistic回归显示，R.E.N.A.L.评分(P≤0.020)和肿瘤边界状态(P=0.001)是cT1期肾细胞癌发生肾窦侵犯的独立危险因素。结论对cT1期肾细胞癌，术后接近15%的患者存在肾窦侵犯现象; R.E.N.A.L.高评分和肿瘤边界不规则，均可以提示cT1期肾细胞癌有发生肾窦侵犯的风险。     

无症状中国年轻人颈椎矢状位曲度正常值及其与全脊柱平衡的关系

目的探讨无症状中国年轻人颈椎矢状位曲度的正常值及其与全脊柱平衡的关系。方法2011年11月—2014年12月招募并选择年龄18~30岁的志愿者行全脊柱侧位X线检查，在X线片上测量指标包括C₀-C₂角、从C₂-C₃到C₆-C₇的间盘角、从C₃到C₇的椎体角、T₁倾斜角、胸椎后凸角(thoracic kyphosis, TK)、腰椎前凸角(lumbar lordosis, LL)、骨盆入射角(pelvic incidence, PI)、骶骨倾斜角(sacral slope, SS)、C₂-C₇矢状轴向垂线(C₂-C₇ sagittal vertical axis, C₂-C₇SVA)、头重心至C₇的矢状位轴向垂线(center of gravity of head to C₇SVA, CGH-C₇SVA)、C₇到S₁的矢状位轴向垂线(C₇-S₁SVA)。依据脊柱骨盆矢状位形态进行Roussouly分型，比较不同Roussouly分型下的颈椎曲度及形态。结果共纳入126名志愿者参与研究，其中男性67名，女性59名，平均年龄(21.4±2.3)岁。C₀-C₇前凸角平均为26.0°±12.8°，其中C₀-C₂前凸角平均为15.2°±6.7°，C₂-C₃到C₆-C₇间盘前凸角总和平均为9.1°±12.1°，C₃到C₇的椎体前凸角总和平均仅为1.4°±10.2°。C₂-C₇SVA(18.6±7.9) mm和CGH-C₇SVA[(22.9±12.3) mm]由C₇-S₁SVA[(-21.6±31.0) mm]完美代偿。不同的Roussouly分型间颈椎曲度差异有统计学意义(P < 0.01)。颈椎曲度与T₁倾斜角(P < 0.01)、胸椎后凸角(P < 0.01)有显着相关性。从T₁倾斜角到C₀-C₂角，相邻节段间盘角之间存在显著相关性(P < 0.05)。结论测量并计算了无症状中国年轻人颈椎椎体角和间盘角的正常值，发现颈椎前凸主要发生在C₀-C₂和椎间盘水平，这些角度受到其他脊柱部位形态(T₁倾斜角、胸椎后凸角和Roussouly分型)的影响，且相邻间盘角之间存在显著的相关性。     

奥氮平连续处理后大鼠中缝背核组织差异表达蛋白的生物信息学分析

目的分析奥氮平连续处理的大鼠中缝背核蛋白的差异表达，探究奥氮平使用早期导致代谢障碍可能的中枢5-HT机制。方法将40只SD大鼠随机分配到奥氮平组[灌胃奥氮平1.2 mg/(kg· d）]和对照组（灌胃等量0.9%氯化钠溶液），两组各分配10只雌性大鼠、10只雄性大鼠。给药1次/d，连续28 d。最后一次给药1 h后处理大鼠，并取大脑中缝背核样本。利用绝对和相对定量同位素标记技术联合液相色谱-串联质谱技术对大鼠中缝背核组织进行蛋白质组学分析，进一步对差异表达蛋白进行GO、KEGG通路、COG、蛋白互作网络分析。另将24只大鼠随机分为4组：2个奥氮平组和2个对照组（6只/组），类似方法得到大鼠中缝背核样本，根据蛋白质组学数据选择目标基因的表达进行qRT-PCR和Western blot验证。结果筛选出奥氮平组与对照组大鼠中缝背核差异表达蛋白有72种上调、142种下调。GO注释分析显示，涉及奥氮平的差异表达蛋白参与细胞过程、生物调节、代谢过程、应激反应、多细胞生物过程以及结合、催化活性、分子功能调节、转录调节活性等分子功能。KEGG富集分析显示，涉及奥氮平的差异表达蛋白主要参与流体剪切应力与动脉粥样硬化、5-羟色胺能突触、丁酸代谢、甲状腺激素合成和IL-17信号通路等；PPI分析显示，涉及奥氮平的差异表达蛋白Hmgcs2、Cav1、Hsp90b1、Canx、Gnai1、MAPK9和LOC685513(Gng14）位于蛋白质互作网络的节点。qRT-PCR和Western blot结果显示，丁酸代谢和5-羟色胺(5-HT）能突触通路4个基因及其蛋白，其中丁酸代谢的关键调节基因Hmgcs2及其蛋白在药物处理组明显下调（P < 0.01），5-羟色胺2受体调控的Slc6a4、Gnai1基因及其蛋白在药物处理组均出现显著高表达（P < 0.05）。结论奥氮平使用早期可能主要通过调控中缝背核组织Hmgcs2、Cav1、Hsp90b1、Canx、Gnai1、Slc6a4、MAPK9和Gng14等差异表达蛋白以及5-HT能突触通路等，参与大鼠机体代谢障碍的中枢5-HT作用机制。     

手臂位置对射波刀放射治疗脊柱肿瘤患者的剂量学影响

目的评估患者手臂位置变化对射波刀脊柱肿瘤放射治疗潜在剂量学的影响。方法选取胸椎与腰椎肿瘤患者各12例，勾画患者手臂轮廓并修改CT值和密度，使其等效为空气，模拟手臂完全移出射野的极端情况。保留原治疗计划的射束条件再次计算剂量，通过与原始计划的剂量体积直方图(dose-volume histogram, DVH)的参数比较，分析计划靶区(planning target volume, PTV)100%处方剂量的覆盖体积(V₁₀₀)、95%PTV体积受照剂量(D₉₅)、90%PTV体积受照剂量(D₉₀)、适形指数(conformity index, CI)与异质性指数(heterogeneity index, HI)，以及脊髓、胃、食管、肠道的最大受照剂量(D_max)、1cc体积(1 mL)受照剂量(D_1cc)和2cc体积(2 mL)受照剂量(D_2cc)的变化。结果与原治疗计划相比，模拟计划的PTV V₁₀₀、D₉₅、D₉₀、CI平均升高0.86%、2.02%、1.97%、0.80%，差异有统计学意义(P < 0.05);脊髓D_max、D_1cc与D_2cc平均升高2.35%、2.59%、1.49%，差异有统计学意义(P < 0.05);胃D_2cc平均升高1.70%，差异有统计学意义(P < 0.05);食管与肠道剂量差异无统计学意义。结论在基于射波刀的脊柱肿瘤放射治疗过程中最极端的双臂位置情况下，发现手臂位置的改变对剂量学影响很小，并且随手臂位置的改变，靶区与危及器官(organ at risk, OAR)的剂量有所增加，但增幅相对较小，因此，在某些特殊情况下，患者确实无法始终保持手臂位置一致时，可以进行合理的调整，但是为了保证剂量的精确投照，应尽可能实现患者治疗体位的稳定性与一致性。     

中危非肌层浸润性膀胱癌的最佳膀胱镜监测强度

目的为中危非肌层浸润性膀胱癌确定最佳的膀胱镜监测频率方法回顾性分析2001年1月至2019年10月于北京大学人民医院行经尿道膀胱肿瘤电切术的中危非肌层浸润性膀胱癌患者，收集患者的临床、病理学和随访资料。术后2年每3至6个月对患者进行膀胱镜检测，根据患者复发和进展的情况，在术后2年假设3种强度的监测策略：模式1：间隔3个月，模式2：间隔6个月，模式3：间隔12个月，比较3种模式间检测复发和进展的延迟个数和时间差异。结果共纳入185例患者，其中男性144例(77.8%)，女性41例(22.2%)，中位年龄68 (59~76)岁。单发肿瘤有118例(63.8%)，多发肿瘤有67例(36.2%)。术后病理Ta期179例(96.8%)，T1期有6例(3.2%)。高级别病变108例(58.4%)，低级别病变77例(41.6%)。在术后2年随访期间内，52例(28.1%)患者出现复发，133例(71.9%)未出现复发；11例(5.9%)患者发生进展，174例(94.1%)未发生进展。相比于模式1，模式2出现复发检测延迟的个数为29例(55.8%)，模式3为41例(78.8%)，两者之间差异有统计学意义(P=0.012)。模式1、模式2和模式3检测复发的中位延迟时间分别为1.00、1.99和4.19个月。模式1与模式2和模式3之间差异均有统计学意义(P=0.001, P=0.013)。与模式1相比，模式2出现进展检测延迟的个数为5例(45.4%)，模式3为8例(72.7%)，两者之间差异无统计学意义。模式1、模式2和模式3检测进展的中位延迟时间分别为1.00、2.00和3.00个月，三者之间差异无统计学意义。结论6个月间隔的膀胱镜检测模式与3个月相比，虽然会稍微延迟检测到肿瘤复发和进展，但不会造成严重的不良结局，并能够减少患者的痛苦和经济负担，在中危非肌层浸润性膀胱癌是可行的。