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目的 探讨真性红细胞增多症（PV）患者干扰素和（或）羟基脲治疗后症状负荷改善与血液学疗效之间的关系。 方法 对190例符合WHO（2016）诊断分型标准、接受干扰素和（或）羟基脲连续治疗≥6个月的PV患者，分别应用外周血细胞计数和骨髓增殖性肿瘤总症状评估量表（MPN-10）评价患者血液学疗效和症状负荷。 结果 全部190例PV患者中，男93例（48.9％），女97例（51.1％）。进行MPN-10评分时，患者中位年龄为60（32～82）岁。全部患者中位MPN-10总分为9（0～67）分，干扰素+羟基脲组（27例）为11（0～67）分，显著高于干扰素组［64例，6（0～56）分，P＝0.019］和羟基脲组［99例，9（0～64）分，P＝0.047］，而干扰素组与羟基脲组差异无统计学意义（P＝0.421）。28.9％（55/190）的患者存在重度症状（单项症状评分≥7分或总分≥44分），干扰素组、羟基脲组、干扰素+羟基脲组重度症状患者占比分别为23.4％、29.3％、40.7％，组间比较差异均无统计学意义（P>0.05）。全部190例患者中，进行MPN-10评分时71例（37.4％）获得完全血液学缓解（CHR），仅55例（28.9％）获得疾病充分控制（获得CHR且无重度症状）。未获得疾病充分控制的患者包括：血细胞增高80例（42.1％），获得CHR但伴重度症状16例（8.4％），血细胞增高且伴重度症状39例（20.5％）。PLT>400×109/L患者中存在重度症状患者比例、MPN-10总分中位数均高于PLT≤400×109/L患者［40.8％（20/49）对24.8％（35/141），P＝0.044；14（0～67）分对7（0～56）分，P＝0.038］。PLT>400×109/L是存在重度症状的危险因素（HR＝2.089，95％CI 1.052～4.147，P＝0.035）。 结论 经干扰素和（或）羟基脲治疗后，PV患者症状负荷未获满意控制仍较突出，部分患者虽然获得CHR，仍存在重度症状负荷。PLT>400×109/L是干扰素和羟基脲治疗后患者存在重度症状的危险因素。

Dys-regulated long noncoding RNAs (lncRNAs) are involved in the cell growth of several malignancies and their aggressive phenotypes. LncRNA DBH-AS1 plays an important role in the advancement of various malignant tumors, but its contribution to non-small cell lung cancer (NSCLC) is still unexplored. This study intends to elucidate the role of the regulatory network of lncRNA DBH-AS1 in NSCLC progression.The LncDBH-AS1 expression in 32 paired NSCLC patients' tissue samples and NSCLC cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The role of LncDBH-AS1 in NSCLC was investigated through cell counting kit-8 (CCK-8) assay and colony formation assay in vitro. Besides, the interaction between LncDBH-AS1 and miR-155 was also analyzed.The DBH-AS1 expression was significantly down-regulated in NSCLC cell lines and tissue samples. Decreased DBH-AS1 levels promoted the in vitro proliferation of the NSCLC cells. The mechanism was that DBH-AS1 regulated AXIN1 expression by sponging miR-155 in NSCLC cell lines. Importantly, LncDBH-AS1 might inhibit WNT/β-CATENIN activation in NSCLC cells.The progression of NSCLC is facilitated by DBH-AS1 via miR-155 interaction and up-regulation of AXIN1 expression.

COVID-19 is an emerging infectious disease caused by SARS-CoV-2. After the infection of the virus, the host immune system is stimulated to produce multifarious specific antibodies to decrease or eliminate effects of the pathogen. Study of the specific antibodies dynamic characteristics in patients with COVID-19 is very important for the understanding and diagnosis of the disease, research and development of vaccine, and planning of prevention and control strategy. This paper reviews and summarizes the domestic and oversea research on dynamic characteristics of specific antibodies of COVID-19 patients, including the antibody producing, duration and level, and its possible influencing factors in order to improve the understanding of the immunological characteristics of COVID-19.新型冠状病毒肺炎是由新型冠状病毒（新冠病毒）引起的新发传染病。新冠病毒侵入人体后，刺激免疫系统产生多种特异性抗体，来减弱或清除病原体对机体的影响。研究新冠病毒感染后人体内特异性抗体动态变化特征对于疾病认识、诊断、以及疫苗研究与防控策略制定具有重要意义。本文对国内外关于新冠病毒感染者不同类型特异性抗体产生和持续时间、抗体水平及其可能的影响因素等方面的相关研究进行归纳分析，从而增进对新冠病毒感染后机体免疫学特征的了解。.

To examine the correlation betweenA total of 228 serum samples collected from women with spontaneous abortion for the first time from January 2018 to December 2019 were selected as the case group, while 228 serum samples collected from pregnant women with a normal delivery and without a history of abortion during the same period were selected as the control group. The serum IgG and IgM antibodies againstThere were no significant differences between the case and control groups in terms of age, education levels, occupation, residency and proportion of keeping cats (allAcute maternal

Background CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy. Patients and methods Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided. Results Median progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46–9.00] months for GP arm and 6.07 (95% CI 5.32–6.83) months for GT arm (P = 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P = 0.008; 10.37 versus 4.30 months, P = 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P = 0.086; 8.90 versus 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks. Conclusions GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients. Trial registration ClinicalTrials.gov, NCT01287624.

患者女，53岁，因发现"右乳肿块1个月余"就诊。肿物直径约1.3 cm，灰白色，质韧。镜下病变界尚清，2/3的区域为硬化性腺病，另1/3的区域硬化性间质中杂乱分布着小腺管以及鳞状分化细胞巢，鳞化细胞巢多呈实性条索状，部分形成大小不等的角化囊肿；病变细胞形态温和，核分裂象罕见，并见淋巴细胞聚集灶，局灶浸润周围组织。免疫组织化学显示该区域内大部分细胞巢周围缺乏p63、calponin及CD10染色，部分鳞状分化巢CK5/6和p63阳性，诊断为乳腺硬化性腺病基础上的低级别腺鳞癌。.

To comprehend clinical features and patient's physician visit patterns at onset of immunoglobulin G4 related disease (IgG4RD).In the study, 100 patients with IgG4RD who received treatments in the Department of Rheumatology and Immunology of Peking University People's Hospital from Apr. 1st, 2017 to Apr. 1st, 2018 were investigated, including gender, age, height, body weight, age of onset, physician visit history, primary history and how did the disease affected their life, etc. RESULTS: In this 100 IgG4RD cohort (57 males and 43 females), the male/female ratio was 1:0.75, the mean age of onset was (51.51±12.9) years, and the median duration was 49 months (ranging from 4 to 231 months). The onset age of males was significantly older than that of females (P0.01). The manifestations showed that up to 69% patients had submaxillay glands lesion, 59% patients had lacrimal glands lesion, 28% patients had pancreas involvement and 28% patients had parotid glands involvement. The females had more lacrimal glands involvement (P0.05). 62% patients were complicated with anaphylactic disease. The primary physician visit departments concentrated upon general surgery department (19/100), oral and maxillofacial surgery department (17/100), rheumatology and immunology department (16/100), ophthalmology department (15/100) and gastroenterology department (10/100). The departments where the confirmed diagnose was made concentrated upon rheumatology department (67/100),oral and maxillofacial surgery department (16/100) and gastroenterology department (7/100). The mean diagnosis duration after 2010 was (16.96±2.163) months, significantly shorter than that before 2010, which was (113.3±11.01) months. Before the definite diagnose was made, 43% patients underwent surgeries and 12% patients had more than one time surgeries. The patients whose first-visit department was a surgery department were more likely to undergo surgeries (P0.01). 18% patients (18/100) stated that the disease had affected their work.In this cohort of the IgG4RD patients, female is common and has earlier onset age than male. The major manifestations of IgG4RD are salivary glands, lacrimal glands and pancreas involvement. The common chief complains are salivary glands and lacrimal glands enlargement. Accompanied by anaphylactic disease is a marked manifestation of this disease. Delayed diagnoses are not rare, though this situation has been improved since 2010, and more attention still should be paid to the disease.

Oridonin, an ent-kaurene diterpenoid isolated from the traditional Chinese herb Rabdosia rubescens, has been reported to be a potent cytotoxic agent against a wide array of cancer cells. However, its effect on human nasopharyngeal carcinoma (NPC) cells has not been well investigated. The present study aimed to explore the anti-tumour effect of oridonin in NPC cells and its underlying mechanisms. Cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and colony formation assay. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and expression of apoptosis-related proteins were analysed by flow cytometry with propidium iodide staining, JC-1 staining, DCFH-DA staining, and Western blot analysis, respectively. The results showed that oridonin concentration-dependently inhibited the cell viability, decreased the colony formation, and enhanced the apoptotic rate in NPC cells. Further, oridonin-induced apoptosis was mediated by the mitochondrial pathway in NPC cells, which was confirmed by the loss of MMP, downregulation of anti-apoptotic Bcl-2 family protein Mcl-1 and Bcl-2, upregulation of pro-apoptotic Bcl-2 family member Bax, and activation of caspase-3 and PARP. Notably, the augmented ROS generation played an essential role in oridonin-induced apoptosis in NPC cells, as the apoptosis-inducing effect was attenuated by ROS scavenger N-acetyl-L-cysteine. These results indicate that oridonin triggers apoptosis through the ROSmediated mitochondrial pathway in NPC cells. This study supports oridonin to be an interesting candidate drug for the treatment of human NPC.

Chinese herbal medicine Jinlianqingre Effervescent Tablets (JET) are the recommended control measure for uncomplicated hand, foot, and mouth disease (HFMD) by the Ministry of Health of China. However, high-quality evidence to support this recommendation is limited. A total of 288 patients ranging in age from 1 to 13 years were randomly assigned to JET in combination with conventional therapy (mainly including the reduction of temperature by applying physical cooling paste or warm bathing), or conventional therapy with placebo group for 7 days. The objective was to test the hypothesis that JET combination therapy is more effective than conventional therapy for uncomplicated HFMD. A randomized, double-blind, placebo-controlled trial was designed. Our study showed that, compared with conventional therapy, the median time to fever resolution was significantly shorter in the JET combination therapy (8 vs. 80 h; p < 0.0001); the risk of fever resolution increased in the JET combination therapy [hazard ratio, 19.8; 95 % confidence interval (CI), 12.8 to 30.7]; the median healing time of rash or oral ulcer was significantly shorter in the JET combination therapy (14 vs. 74 h; p < 0.0001); and the median symptom score for skin or oral mucosa lesions improved more rapidly in the JET combination therapy during the follow-up period. The median duration of hospital stay was 6 days in the JET combination therapy and 7 days in the conventional therapy (p < 0.0001). No significant adverse events and complications were found in both groups. The addition of JET to conventional therapy reduced fever clearance time, healing time of skin or oral mucosa lesions, and duration of hospital stay in children with uncomplicated HFMD.

To evaluate the hepatitis A vaccine coverage among 2-29 year olds and the reported incidence rates of hepatitis A, in China.Based on data from the national sero-survey on hepatitis B in 2014, information on hepatitis A vaccine immunization was collected and the coverage of hepatitis A vaccine was analyzed with SAS software (Version 9.4). Incidence data on hepatitis A was also collected from the National Notifiable Disease Reporting System between 2004 and 2014, and analyzed using the micro-software Excel 2007.Totally, data involving 29 058 people aged 2-29 years were available for analysis and the overall hepatitis A vaccine coverage was 44.6%. The younger the age, the higher the coverage appeared. Among the 2-6 year and the 7-14 year olds, rates of hepatitis A vaccine coverage were 91.2% and 76.0% respectively. From 2004 to 2014, the incidence rates of hepatitis A in the whole population were declining, annually. The incidence rates showed continuously declining as 82.5%, 90.6%, 72.1% among children at the age groups of 2-6 years, 7-14 years and in the whole population, from 2007 to 2013.After the inclusion of hepatitis A vaccine into the Expanded Programe on Immunization (EPI), the coverage of hepatitis A vaccine among the 2-6 year olds increased to over 90%, with no obvious difference between the urban and rural areas. Incidence of hepatitis A in the 2-6 year olds showed a more rapid decline than that in the whole population.

We describe the epidemiology of hepatitis B virus (HBV) infection among women of reproductive age residing in areas of China that are highly endemic for chronic HBV, and provide evidence useful for decision-makers to guide strategies for preventing mother-to-child transmission of HBV, and assess the impact of perinatal transmission PMTCT by projecting HBsAg prevalence trends without interventions. We conducted a cross-sectional HBV serological survey of women, 15-49 years of age, residing in Fujian, Guangdong, Guangxi and Hainan provinces. Demographic and other subject-level data were collected in face-to-face interviews, after which we obtain blood specimens. Specimens were tested for HBV sero-markers by ELISA (Beijing Wantai Biological Pharmacy), and HBV DNA was tested with PCR (Hunan Sansure Biotech). Weighted HBsAg and HBV (either HBsAg+ or anti-HBc+ indicating either present or past infection) prevalences were 11.82% and 57.16%, respectively. Among the HBsAg-positive women, 27% were also HBeAg positive. The proportion of individuals with HBV DNA loads >105 IU/mL declined with increasing age. Among HBsAg-negative women, 0.9% had occult HBV infection. The prevalence of chronic HBV infection among reproductive women in these highly endemic provinces is high, posing a threat to maternal health and risk of mother-to-child transmission. Prevention of mother-to-child transmission remains critically important.

Esophageal Squamous Cell Carcinoma (ESCC) is one of the most common human cancers with a particularly high incidence in certain regions of China. Differentially expressed genes (DEG) between the esophageal squamous carcinoma tissues and matched normal esophageal mucosal epithelial tissues can be detected by employing the gene microarray technology. This can aid the analysis of the underlying disease mechanism and can help to identify potentially critical genes as well as related molecular signalling pathways.The potentially critical genes and related signal pathways are examined by bioinformatics analysis including Gene Ontology (GO) analysis, pathway analysis and signal transduction networks. Here, we performed microarray analysis with 8 pairs of ESCC and normal esophageal mucosal epithelial tissues.Compared to the control group, 347 and 203 genes were found to be up-regulated and down-regulated in the experimental group, respectively. Based on pathway analysis, 52 and 51 signal transduction pathways were involved in the up-regulated and the down-regulated genes, respectively. SLC27A6, RAB11A, ABCA8, JAM2, HNMT, GSTM1, and CDKN3, which play critical roles in regulating the expression of ESCC, were identified among the key genes involved in the signal transduction networks.Investigation of the mechanism underlying ESCC can provide a direction for the clinical prevention and treatment of ESCC.

The purpose of the study was to compare psychometric properties of the EQ-5D-5L (5L) and the EQ-5D-3L (3L) health outcomes assessment instruments in patients with hepatitis B in China. Patients, including hepatitis B virus carriers and those with active or inactive chronic hepatitis B, compensated cirrhosis, decompensated cirrhosis or hepatocellular carcinoma, answered a questionnaire composed of 5L, socio-demographic information, 3L, and the visual analog scale (VAS), respectively. After 1 week, a retest was conducted for inpatients. We compared acceptability, face validity, redistribution properties, convergent validity, known-group validity, discriminatory power, ceiling effect, test–retest reliability, and responsiveness of 5L and 3L. A total of 369 outpatients and 276 inpatients were recruited for the first interview. Of the inpatients, 183 were used in the retest. Most patients preferred 5L–3L. The 3L–5L response pairs had an inconsistency rate of 2.4 %. Correlation with the VAS was greater with 5L than with 3L. Age, education, and comorbidity were associated with health-related quality of life (HRQoL). 5L discriminated more infectious conditions than 3L. In all dimensions, the Shannon’s index from 5L was larger while in three dimensions the Shannon’s evenness index from 5L was slightly larger. The ceiling effect was reduced in 5L. In patients with stable health states, no significant difference was detected in the weighted kappa between 5L and 3L, but intraclass correlation coefficient of 5L was higher than that of 3L. In patients with improved health states, HRQoL was seen as increased in both 5L and 3L, without significant difference. The EQ-5D-5L was more suitable than the EQ-5D-3L in the patients with hepatitis B in China.

To analyze the studies on decompression illness (DCI) in China in the past 10 years.We searched three Chinese databases and collected studies on DCI for further analysis. On the basis of findings, we proposed the issues on DCI in China.There are more than 50,000 active divers in China, the majority of whom are fishing divers. Among them, the incidence of DCI is still at a high level because they have little or no knowledge of diving and diving medicine, the quality of diving equipment is poor, and divers generally do not follow the regulations of diving. There are few dive physicians in China, and the general clinicians have poor knowledge about, or pay little attention to, dive medicine. This might be the major cause of the poor quality of studies on DCI. There is no consensus in the classification of DCI and treatment tables for DCI treatment. These are factors affecting systemic review and further meta-analysis of available studies on DCI.It is imperative to generalize knowledge in not only divers and diving-related practitioners but general practitioners as well.

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) have been described as two major subtypes of Guillain-Barré syndrome (GBS); however, the possible difference of their immune-inflammatory pathogenesis remains unclear.In this study, by using FACS and enzyme-linked immunosorbent assays analyses, the role of Th1 cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-12 (IL-12) and their receptors on peripheral blood mononuclear cells (PBMCs) and in serum concentrations were investigated in AIDP and AMAN.The results showed enhanced IL-12, IL-12R1 in AIDP and TNF-alpha in AMAN during the acute phase, as well as increased TNF-alpha and TNFR1 during the plateau phase of AIDP. Intravenous high dose immunoglobulin decreased IL-12R1 expression on cells in AIDP, but increased TNF-alpha and TNFR2 in AMAN.Our data suggest that IL-12 promotes disease development in AIDP and in contrast to previously inflammatory assumptions, TNF-alpha may play double roles in GBS. The anti-inflammatory role of TNF-alpha realized through TNFR2 in AMAN is possibly a therapeutic mechanism in the IVIg treatment of AMAN.

Objective: To conduct a large population-based survey on multiple sclerosis (MS) prevalence in Shanghai, China. Methods: We established a network of physicians, mainly neurologists, for identifying prevalent patients with MS and systematically checked inpatient registers at each hospital in the study area for patients with a diagnosis of MS, neuromyelitis optica, or other demyelinating disorders. MS diagnosis in patients was validated by senior neurologists according to the McDonald criteria. Results: In total, 123 patients with a validated MS diagnosis from the study population, 8.86 million inhabitants with permanent residence in Shanghai, were alive on the prevalence day. The crude MS prevalence rate was 1.39 cases per 100,000 inhabitants (95% CI: 1.16 to 1.66 cases) in the study population in Shanghai. There were 79 female and 44 male patients with MS, a female-to-male ratio of 1.8. Nearly all (96%) of the patients with validated MS had been examined by MRI. Conclusion: Multiple sclerosis prevalence in Shanghai is in line with that reported for other Asian populations.

Anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, are frequently over-expressed in human malignancies, and this is correlated with resistance to chemotherapeutic drugs and gamma- radiation. Recently identified small organic molecules capable of inhibiting Bcl-2 and/or Bcl-xL function, may enhance radiation sensitivity of cancer cells in which they are over expressed. We examined whether specific blockade of the BH3-domain binding to Bcl-xL could sensitize cancer cells to gamma- radiation.Human non-small-cell lung cancer H460 cells with wild-type p53 and H1792 cells with mutant p53 were exposed to various doses of radiation and/or BH3I-1 and for different points of time to BH3I-1 treatment. XTT and clonogenic survival assays were used to evaluate the growth-inhibitory effects of the antagonist BH3I-1, ionizing radiation or both. Western blot analysis was used to examine the cellular effect of the expression of Bcl-xL, Bax, and p53. Apoptosis and cell cycle distribution were analyzed by confocal microscopy with Hoechst 33258 staining and cytochrome c, and flow cytometry, respectively.BH3I-1 appeared to induce a dose- and time-dependent apoptosis in H460 and H1792 cells, regardless of p53 status. After 2 days of BH3I-1 treatment, the cells that remained attached were exposed to ionizing radiation. Followed by clonogenic assay, BH3I-1 treatment enhanced the radiation sensitivity of H1792 surviving cells with mutant p53, but not in H460 cells with wild-type p53. A transient time-dependent cell cycle blockade at G2-M phase was identified for H1792 cells without subsequent modification of cell cycle distribution.These findings suggest a potential role for the small molecule inhibitor as a novel radiation sensitizer in non-small cell lung cancer.

The duration of QRS wave, P wave and T wave of ECG can be computerized and auto-detected with digital signal process and wave recognition technology. It can diagnose 15 kinds of abnormal ECG such as ventricular presystole automatically and print out corresponding diagnosis reports. In order to verify the system's stability and creditability, we used American MIT-BIH database to test our algorithms and got a good result.

The cellular DNA contents of 139 bladder irrigations from 52 cases of bladder tumors were determined by flow cytometry. The results were compared with those of pathological grading and exfoliative cytology. It is suggested that cytological results were less accurate than DNA contents. High aneuploid DNA contents in tumor cells were marked by low grade and deep penetration of the bladder tumor. Total cystectomy was needed for bladder tumor with high aneuploid DNA, and partial cystectomy and TURBT for that tumor showed high recurrence with instillation of BCG. The results showed that DNA content of tumor is correlated with the nuclear grade, especially in poorly differentiated neoplasms, but flow cytometry can not replace cystoscopy examination.

Insulin-stimulated autophosphorylation of the cytoplasmic juxtamembrane region of the human insulin receptor was examined by Tricine/SDS-PAGE. Various mutant receptor molecules were used to identify two tryptic phosphopeptides associated with the juxtamembrane region which accounts for 15% of the autophosphorylation of partially purified insulin receptor. These phosphopeptides were immunoprecipitated with an antipeptide antibody against the juxtamembrane sequence and were phosphorylated exclusively on tyrosine. Substitution of both Tyr960 and Tyr953 with alanine eliminated insulin-stimulated phosphorylation of the juxtamembrane region without affecting tyrosine autophosphorylation in the C terminus or regulatory regions. Monosubstitution of Tyr960 with phenylalanine or alanine reduced phosphorylation in the juxtamembrane region by more than 50%, and manual Edman degradation indicated that Tyr960 was phosphorylated in wild-type receptor. In vivo, phosphorylation of the juxtamembrane region accounts for one-third of the insulin receptor phosphorylation and contains both phosphoserine and phosphotyrosine. Deletion of Tyr960 and 11 adjacent amino acids eliminated insulin-stimulated phosphorylation of the juxtamembrane region. Substitution of Tyr960 reduced this phosphorylation by more than 50%. The insulin receptor also undergoes serine phosphorylation outside of the juxtamembrane region which depends on the presence of Tyr1151. Together with our previous studies, this report suggests that phosphorylation of Tyr960 may play an important role in signal transduction by the insulin receptor.