Volume 95  ·  Issue 31  ·  2015

Medicine is a science and art that evolves constantly with the progress of human society and the development of science and technology. It is endowed with new connotations in the evolution of human history. From the farming age, the industrialization age to the information age, medicine has its remarkable characteristics in every historical stage. In the 21st century, the deep integration of modern science and technology with information technology as the core and medicine has promoted the profound change of traditional medical concepts and medical paradigms, and opened a new medical era characterized by precision^[1,2,3,4]。

The plan for precision medicine (precision medicine) was proposed in the 2015 State of the Union address of the United States, which attracted widespread attention in the global biomedical field once it was proposed^[1]。 For a long time, due to the complexity of individuals and the uncertainty of efficacy, clinicians' diagnosis and treatment strategies for diseases are still at the stage of combining objective examination and evaluation with empirical analysis. However, with the rapid progress of genome sequencing technology and the cross application of bioinformatics and big data science, precision medicine is naturally at the forefront of tumor treatment. China is a major country of hepatocellular carcinoma (HCC, referred to as liver cancer for short). The incidence of liver cancer accounts for the fifth in the world, and the cause of death ranks the third. Among them, middle-aged people aged 35-65 are the predominant, and men are more common^[2,3]。 At present, there are many treatment options for liver cancer, including liver transplantation, liver resection, radiofrequency ablation, transarterial chemoembolization, molecular targeting, radiotherapy and systemic chemotherapy. Surgical resection is still the first choice for the treatment of liver cancer, but the recurrence rate of metastasis is as high as 61.5% after 5 years^[4]Therefore, the prevention and treatment of metastasis and recurrence is the key link to prolong the postoperative survival of liver cancer patients. Liver surgery has entered the era of modern surgery, and the concept of precision medicine has provided a brand-new idea for the diagnosis and treatment of liver cancer.

"precision medicine" is a hot word in the current medical field. At the beginning of the new year 2015, President Barack Obama announced the launch of the "Precision Medicine" program in his State of the Union address, and further explained the specifics of the program 10 days later^[1]。 At the same time, Francis Collins, director of the National Institutes of Health (NIH), wrote in the New England Journal of Medicine (The New England Journal of Medicine,NEJM) wrote a detailed account of Obama's precision medicine plan^[2]。 Obama's vision of "precision medicine" is to "make matching cancer therapies by genes as standardized as matching blood groups for blood transfusions, make finding the right dosage as simple as measuring body temperature, in short, give the right therapy to the right people at the right time, every time"^[3]。 Throughout the so-called "precision medicine" of Obama and Collins, it is based on "precise" gene sequencing, "accurately" determining the pathogenesis of tumors, "accurately" developing or matching the corresponding targeted therapeutic drugs, and finally achieving "precise" medication. In short, the American version of "precision medicine" is mainly based on tumor molecular typing and targeted therapy at the gene level.

The surgical treatment of pancreatic head cancer has a history of nearly a hundred years, and it has been very mature in basic surgical procedures and digestive tract reconstruction methods. In the past 20 years, under the guidance of evidence-based medicine theory, the disputes on the surgical indications, resection scope and complication definition standards of pancreatic head cancer have gradually reached a consensus, and the surgical technique has reached the extreme day by day. The continuous development and application of combined organ resection, combined vascular resection, expanded lymph dissection and other techniques have greatly improved the surgical resection rate, while the perioperative mortality rate and complication rate have not increased significantly, reflecting the progress of surgical technique and perioperative management. However, in contrast to the aforementioned progress, the overall prognosis of patients has not improved significantly, and the median survival of patients who can be surgically resected is only 21 months. Pancreatic cancer has the worst prognosis among all digestive tract tumors, and its diagnosis and treatment are extremely challenging. Against the above background, the treatment principle of "individualization" has been emphasized in the past 10 years, and the treatment model has gradually transitioned from "surgery first" to "multidisciplinary collaboration (MDT)", and in recent years has risen to the precision concept. Its core is still to select the right patients and administer the right treatment at the right time^[1]。 The purpose of "precision" is to maximize the benefit of patients, not only to avoid insufficient treatment, but also to avoid overtreatment.

Precision medicine is the trend of medical development in the 21st century, and precision surgery is an important part of precision medicine^[1,2]。 Achieving maxillofacial functional reconstruction and accurate restoration of patient's appearance is the goal of maxillofacial prostheticians, which requires the application of the most accurate medical technology. In the past 20 years, maxillofacial defect repair has gradually entered the digital era, from extensive experience repair to digital precise repair, which has significantly improved the treatment level^[3,4]。 This article reviews and prospects three key problems in digital precise repair of oral and maxillofacial defects.

It is generally believed that modern Western medicine began in the Renaissance, and has become more and more mature after several hundred years of development. It has gradually evolved from Bacon's "empiricism" to translational medicine, systematic medicine and social medicine model based on modern science, which covers humanistic care. These developments have brought revolutionary changes to human society, from extending life span to improving the public health system, and making great progress in disease prevention and control. Even for malignant tumors, such as melanoma, leukemia, breast cancer, lung cancer, liver cancer, etc., the early diagnosis rate and patient survival of these tumors have been encouragingly improved^[1]。 However, with the progress of Western medicine, its shortcomings are gradually revealed. It is the research aimed at these shortcomings that further promotes the development of modern medicine. Although the concept of individualized treatment has been put forward long ago, it has little effect in practical application, especially in western medicine. In the past, we put too much emphasis on guidelines, consensus, and evidence-based medicine, but ignored individual differences. The improvement of sequencing technology, the rapid development of molecular biology, immunology and other disciplines make medicine hopeful for further development and breakthroughs in our era^[2]。

Neurology itself is a combination of multiple disciplines to study nervous system and skeletal muscle diseases. It is the most active clinical medical discipline today. Therefore, its development will surely be combined with the latest ideas and technologies. Several milestones in neurology are related to the cross-fusion of research results in other disciplines, such as computed tomography (CT), X-ray transmission and integrated computer technology in the 1970s, which enabled neurologists to accurately observe the normal and abnormal morphological structures of different parts of the living brain for the first time. Magnetic resonance imaging (MRI) technology, which combines physics, mathematics and computer technology, was widely used in the late 1980s. It can more precisely observe the spinal cord structures and lesions that cannot be observed by CT technology, and can also detect cerebrospinal cord lesions earlier than CT technology, especially those in the early stage of ischemia, which greatly improves the diagnosis and treatment level of neurological diseases. Nowadays, with the progress made in the fields of neuromicropathology, molecular imaging, neurobiology, neuroimmunity, gene and proteomics, let us understand the etiology and pathogenesis of neurological diseases from various levels; The development of nerve radiation and interventional technology has provided new diagnosis and treatment methods for many diseases. The research on gene and protein molecules has promoted the development of neuropharmacology, and great progress has been made in drug research and development, all of which have provided a basis for individualized drug treatment. Stem cell technology provides new hope for the treatment of neurological diseases, and the research on neural networks and functional reconstruction, as well as the development of intelligent rehabilitation devices combined with new materials, make stroke patients expected to get more accurate neurological rehabilitation. Based on the great development of neuroscience and related disciplines, the diagnosis and treatment of neurological diseases should be integrated and accurate^[1,2]。

Today, in the 21st century, clinical oncology has made remarkable achievements. Long-term survival with tumors in many tumors is no longer a dream. The past half century has witnessed the prolongation of the survival of cancer patients, the diversification of cancer treatment methods and the individualization of cancer treatment. The emphasis on patients' quality of life is also constantly promoting the optimization of treatment methods and the research and development of new drugs. With the further development of biomedical technology, the continuous update of tumor treatment concepts and the rapid development of anti-tumor drugs, cancer patients will surely usher in a new dawn, and tumor treatment will usher in a new era-precision treatment.

Orthopedic precision medicine is based on empirical medicine and evidence-based medicine. Compared with individualized medicine, it pays more attention to the characteristics of disease depth and the high accuracy of surgery and drugs. It is more operable and implementable, and has the characteristics of forward-looking, accurate, preventive, individual, minimally invasive, comprehensive and convenient. The orthopedic precision medicine process roughly includes: gene sequencing to find therapeutic targets, big data biotechnology analysis and classification, precision surgery and drug therapy intervention, and precision rehabilitation efficacy tracking and adjustment, and finally promote precision medicine for innovative diagnosis and treatment of orthopedic diseases, so as to improve diagnosis and treatment efficiency, reduce patient pain, reduce economic expenses, and optimize resource allocation.

To evaluate the efficacy of limited margins intensity–modulated radiotherapy (IMRT) with temozolomide chemotherapy in patients with malignant glioma, and explore the prognostic factors of malignant glioma.

A total of 33 whole–resected patients, 14 partial–resected patients and 3 biopsied patients were randomly divided into limited margins group and routine margins group.The patients were treated with IMRT and temozolomide concurrent chemotherapy, subsequently adjuvant chemotherapy.Then all the patients were evaluated 2 months later after concurrent chemoradiotherapy.Progression–free survival in 1 year (PFS–1), progress free survival rate in 1 year (PFSR–1) and 1 year survival rate (SR–1) were recorded.All the possible prognostic factors were analyzed.

Routine margins group: complete response (CR) 19, partial response (PR) 2, stable disease (SD) 2, progressive disease (PD) 2; Limited margins group: CR 16, PR 6, SD 1, PD 2.Mean PFS–1 of the two groups were 11.64 and 11.36 months, respectively.PFSR–1 were 84% in routine margins group and 80% in limited margins group.SR–1 of two groups were both 100%.Surgery results and O6–methylguanine–DNA methyltransferase (MGMT) promoter methylation status were correlated with immediate–term prognosis by either univariate or multivariate analysis.Both surgery results and immediate–term prognosis were relevant factors to PFS–1.Progression sites in two groups had no statistical difference by analysis.

Both groups gained favorable results, and limited margins doesn't increase local failures.Surgery results are important prognostic factors to immediate–term prognosis and PFS–1.

To evaluate the clinical application value of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in judging infarction time phase of acute ischemic cerebral infarction.

To retrospective analysis DTI images of 52 patients with unilateral acute ischemic cerebral infarction (hyper-acute, acute and sub-acute) from the Affiliated Yancheng Hospital of Southeast University Medical College, which diagnosed by clinic and magnetic resonance imaging.Set the regions of interest (ROIs) of infarction lesions, brain tissue close to infarction lesions and corresponding contra (contralateral normal brain tissue) on DTI parameters mapping of fractional anisotropy (FA), volume ratio anisotropy (VRA), average diffusion coefficient (DCavg) and exponential attenuation (Exat), record the parameters values of ROIs and calculate the relative parameters value of infarction lesion to contra.Meanwhile, reconstruct the DTT images based on the seed points (infarction lesion and contra). The study compared each parameter value of infarction lesions, brain tissue close to infarction lesions and corresponding contra, also analysed the differences of relative parameters values in different infarction time phases.

The DTT images of acute ischemic cerebral infarction in each time phase could show the manifestation of fasciculi damaged.The DCavg value of cerebral infarction lesions was lower and the Exat value was higher than contra in each infarction time phase (P<0.05). The FA and VRA value of cerebral infarction lesions were reduced than contra only in acute and sub-acute infarction (P<0.05). The FA, VRA and Exat value of brain tissue close to infarction lesions were increased and DCavg value was decreased than contra in hyper-acute infarction (P<0.05). There were no statistic differences of FA, VRA, DCavg and Exat value of brain tissue close to infarction lesions in acute and sub-acute infarction. The relative FA and VRA value of infarction lesion to contra gradually decreased from hyper-acute to sub-acute cerebral infarction (P<0.05), but there were no difference of the relative VRA value between acute and sub-acute cerebral infarction.The relative DCavg value of infarction lesion to contra in hyper-acute infarction than that in acute and sub-acute infarction (P<0.05), however there was also no difference between acute and sub-acute infarction.ROC curve showed the best diagnosis cut off value of relative FA, VRA and DCavg of infarction lesions to contra were 0.852, 0.886 and 0.541 between hyper-acute and acute cerebral infarction, the best diagnosis cut off value of relative FA was 0.595 between acute and sub-acute cerebral infarction, respectively.

The FA, VRA, DCavg and Exat value have specific change mode in acute ischemic cerebral infarction of different infarction time phases, which can be combine used in judging infarction time phase of acute ischemic cerebral infarction without clear onset time, thus to help selecting the reasonable treatment protocols.

To identify differentially expressed genes in Modic changes by gene microarray method.

From August 2014 to December 2014, gene expression profiling analysis of 5 lumbar endplates with Modic changes and 5 control specimens without Modic changes were performed in Department of Orthopaedics, Zheng Linhai Second People's Hospital and Department of Orthopaedics, Shanghai Jiaotong University School of Medicine.The functional analysis (Gene Ontology and KEGG) of deregulated genes was carried out.The qRT-PCR analysis was performed to validate differential expression genes.

Of 263 significantly differential expression genes (P<0.05, Fold Change> 2), 107 were over-expressed and 156 under-expressed genes.Those deregulated genes were mainly involved in chemotaxis and cell motion.The qRT-PCR analysis of 2 up-regulated genes (CXCL14, KCNMA1) and 4 under-regulated genes (MARCKS, ZEB2, PSMF1, and CNN2) mRNA expression levels validated the results from the microarray analysis.

There are differentially expressed genes between lumbar endplate with Modic changes and without Modic changes.Modic changes may be multiple genes involved and regulated pathological changes.

To assess the use of Physical and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) scoring system in predicting outcomes of patients undergoing orthopedic surgery and provide guidance for operation treatment decisions.

From April 2009 to September 2010, a total of 779 cases went operation in Beijing Hospital were collected.They were divided into two groups according to the presence or absence of complications.The patients' postoperative complications were predicted by POSSUM and compared to the actual morbidity to verify the effectiveness of the equation.Logistic regression was taken to make appropriate improvements for the POSSUM equation.ROC curve was drawn to describe the compliance of the original and new equations.

In the 779 cases, the morbidity predicted by POSSUM is 212 cases while the actual morbidity is 65 cases.Of all risk factors, echocardiography ejection fraction showed a close relationship with postoperative complications(P<0.01). In the original equation, actual complication group compared with non–complication group, the difference was statistically significant (P<0.01). In the modified equation, complication group compared with non–complication group, the difference was statistically significant (P<0.01). Compared with the original one , the modified POSSUM had better predictive value on postoperative morbidity, and the comparison of AUC between the two groups was statistically significant ((0.67±0.12)vs (0.75±0.08),P<0.01).

POSSUM over predicted morbidity of patients undergoing orthopedic surgery, it can be more accurate when modified appropriately.

To discuss the feasibility and advantages of aberrant incision location of single–port video–assisted thoracoscopic surgery(VATS) in different gender when treating some lung diseases.

Retrospectively analyze the clinical data of these patients who were received lung partial resection from the same surgeon in the First Affiliated Hospital of Soochow University, the 100 Hospital of PLA, Wu Zhong People's Hospital from January 2012 to December 2014.Among the males, 57 were undertook a single–port VATS surgery through areola incision(Observation Group A), and the rest 114 were received conventional uniportal VATS surgery(Control Group A). Among the females, 15 were operated through the subxiphoid incision(Observation Group B) and 45 were received conventional one(Control Group B). The operation time, blood loss, postoperative drainage amount, chest tube drainage duration, postoperative hospital stay, the Visual Analogue Scale(VAS) pain score of the 1st and 2nd postoperative day, the incision discomfort in the 30th and 90th postoperative day, and the incision satisfaction degree were evaluated.

All the patients were underwent total VATS surgery successfully and no severe complications were observed.In males, there were no significant differences in operation time, blood loss, postoperative drainage amount, chest tube drainage duration, postoperative hospital day and the VAS score of the 1st postoperative day(P>0.05). Compared to control group A, the VAS score of the 2nd postoperative day was lower(3.56±1.78 vs 4.14±1.62,P=0.035), the incision discomfort of 30th and 90th postoperative day was reduced (33(57.9%) vs 86(75.4%), P=0.019; 29(50.9%) vs 76(66.7%), P=0.046) and the incision satisfaction degree was significantly improved(45(79.0%) vs 61(53.5%), P=0.001). In females, there were no statistical differences in intraoperative blood loss, postoperative drainage amount, chest tube drainage duration, postoperative hospital day and the incision satisfaction degree(P>0.05). Compared to control group B, the operation time was obviously prolonged(57.67±5.72 vs 42.91±7.82,P=0.000), the VAS score of the 1st and 2nd postoperative day was significantly lower(2.13±1.06 vs 3.84±1.69, P=0.001; 2.60±1.24 vs 4.18±1.56, P=0.001) and the incision discomfort in 30th and 90th postoperative day was reduced(4(26.7%) vs 34(75.6%), P=0.001; 4(26.7%) vs 28(62.2%), P=0.017).

In single–port VATS surgery for some pulmonary diseases, we choose"individualized"incision location––trans–areola incision in males and subxiphoid incision in females––according to different gender and varieties of diseases, which was considered to raise incision satisfaction degree in males and reduce postoperative pain in females, it warrants further clinical practice.

The clinical features and two disease activity assessment methods of Behçet's disease were evaluated in order to guide clinical management.

A total of 116 patients with Behçet's disease from China-Japan Union Hospital of Jilin University in 2007–2014 were analyzed retrospectively for the gender and age distribution as well as clinical features of multisystem involvement.The correlations of Behçet's Disease Current Activity Form (BDCAF) and electronic medical record (EMR)-based activity index (EMRAI) scoring systems with clinical data were compared in Chinese patients for the first time, and clinical suggestion was raised.

Behçet's disease was commonly seen in young adults with age between 21–40 years old with mean course of four years.Males had longer duration than females(9.5 years vs 4.0 years,P<0.05=, and vasculopathy was more commonly seen in males (11.9% vs 1.36%,P<0.05=, while females had wider age distribution.BDCAF and EMRAI scoring systems were positively correlated with each other; the former was well associated with laboratory inflammatory indices, and the latter was simplified for application.

The clinical manifestation of Behçet's disease varies with different gender; BDCAF and EMRAI scoring system well correlate with the laboratory inflammatory indices of patients, and can indicate the disease activity.

To evaluate the intrauterine state of fetuses with pregnancy–induced hypertension (PIH) through quantitative measurement of placenta by three–dimensional power Doppler ultrasonography, and to judge the value of three–dimensional power Doppler in PIH fetuses.

A total of 50 pregnant women with PIH in our hospital from November 2012 to August 2014 were enrolled into the observation group, while 50 cases were randomly selected into the control group to match the former group's gestational week (GA). The placental vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were quantitatively measured by three–dimensional power Doppler ultrasonography in the two groups.SPSS 19 statistics software was used to do the linear regression for the above parameters.And those parameters of the two groups were compared byt test.P<0.05 was deemed significant.

The detection ratio of fetal placental VI, FI and VFI of the whole 100 cases was 100%.The regression equation of VI and GA was: Y=0.394X–5.358, R²=0.694, P<0.05; the regression equation of FI and GA was: Y=0.801X+ 5.61, R²=0.807, P<0.05; the regression equation of VFI and GA was: Y=0.225X–4.148, R²=0.691, P<0.05.t tests showed the differences of the means of placental VI, FI and VFI between the observation group and the control group were statistically significant (all P<0.05).

VI, FI and VFI of placenta measured by three–dimensional power Doppler examination increase with the increase of GA, and the means of placental VI, FI and VFI in PIH patients are less than those in normal cases.Quantitative measurement of placenta with three–dimensional power Doppler ultrasound has its own advantages, and can evaluate the status of placenta of PIH fetus accurately.

To investigate the efficiency of uterine arterial embolization in induced labour among pregnant women with placenta previa.

All pregnant women (20 cases) with placenta previa who received induced labour in Taizhou First People's Hospital between 2009 and 2014 were included in this retrospective study.All cases were given rivanol induction combined with uterine arterial embolization and mifepristone.The antepartum and postpartum history were reviewed.

16 cases out of 20 delivered vaginally with small amount of bleeding.The other 4 cases got emergency cesarean delivery because of uncontrolled vaginal bleeding.No case needed hysterectomy.The average interval between the procedure and menstruation recover was 42 days.

Uterine arterial embolization improves the efficiency of induced labour and shows advantages to postpartum haemorrhage and prevent infertility.Uterine arterial embolization is recommended as a effective management for pregnancies with placenta previa state.

We assessed serum procalcitonin (PCT) levels to distinguish bacterial infections from non–bacterial infections in patients with fever and flare of chronic gouty arthritis.

One hundred febrile patients with chronic tophaceous gout flare–ups were collected consecutively between November 2011 and January 2014 from the Department of Rheumatology and Immunology, Sichuan Provincial People's Hospital. These patients were divided into non–infectious febrile group (68 patients) and bacterial infectious febrile group (32 patients, including 6 cases of pulmonary infection, 3 cases of infectious arthritis and 21 cases of skin infection, 2 patients died from severe infection were excluded), and 30 patients with flare of chronic gouty arthritis without fever and infection. Serum PCT, erythrocyte sedimentation rate (ESR), C–reactive protein (CRP), white blood cell (WBC) count and neutrophil ratio were determined.

57.3% (39/68) patients in the non–infectious febrile group had PCT levels≥0.5×10³ ng/L and the ratio in the infectious febrile group was 66.7% (20/30) . No statistically significant difference was detected between them (P>0.05). 16.7% (5/30) patients had PCT levels≥0.5×10³ ng/L in the afebrile group and both the differences between the afebrile group and the two febrile groups were significant (P<0.05). The differences of ESR, CRP, WBC count and neutrophil ratio between the two febrile groups were not statistically significant (P>0.05). In the chronic gouty arthritis patients with fever, the sensitivity and specificity of high PCT level (≥0.5×10³ ng/L) for detection of bacterial infections was 33.9% and 74.4%, the positive predictive value was 36.9% and the negative predictive value was 71.9%. The area under the curve (AUC) of PCT, CRP, ESR, WBC count and neutrophil ratio in patients with fever and chronic gouty arthritis was 0.598, 0.636, 0.612, 0.596 and 0.727, respectively.

Serum PCT levels may be not a good marker for detection of bacterial infections in the patients with fever and flare of chronic gouty arthritis. Larger studies are needed to evaluate the value of PCT measurement in the patients with fever and flare of chronic gouty arthritis.

To investigate the effects of blueberry on the apoptosis, expression of Bcl–2 and Bax in rat hepatic stellate cell (HSC–T6).

10% blueberry serum at low, middle and high dose, 10% Fu–Fang–Bie–Jia–Ruan–Gan tablet serum and 10% saline serum were prepared by method of serum pharmacology.Subcultured HSC–T6 was divided into saline serum control group, blueberry serum at low, middle, high dose and Fu–Fang–Bie–Jia–Ruan–Gan tablet serum group, and then was respectively incubated at different dose of 10% blueberry serum, 10% Fu–Fang–Bie–Jia–Ruan–Gan tablet serum and 10% saline serum for 72 hours.Apoptosis of HSC–T6 was detected using flow cytometry with annexin V FITC/PI double staining.The expression of Bcl–2 and Bax in HSC–T6 were examined using immunocytochemistry and Western blotting, respectively.

There was no significant difference for HSC–T6 Bax protein expression in the low, middle and high dose blueberry serum groups, compared with saline serum control group, respectively.In the high–dose blueberry serum group HSC–T6 early and total apoptosis rate increased significantly compared with the saline serum control group (5.55%±0.98% vs 2.53%±0.46%, 7.01%±1.05% vs 2.96%±0.81%, both P<0.05); Bcl–2 protein expression was significantly decreased (A value, 82±35 vs 51±13, P<0.05); Bcl–2/Bax ratio was significantly decreased (0.26±0.02 vs 0.46±0.03,P<0.05); HSC–T6 early and total apoptosis rate, Bcl–2 expression and Bcl–2/Bax ratio in the low and the middle dose blueberry serum group showed no significant difference with the saline serum control group.

Blueberry can induce HSC–T6 apoptosis by down–regulating Bcl–2 expression and decreasing the ratio of Bcl–2/Bax in HSC–T6 cells, so it may have potential interference effects on hepatic fibrosis.

The structure of the hand is delicate and complicated, with tendons, blood vessels and nerves interspersed. Once injury occurs, tissue damage is serious and pain is severe^[1]。 Patients need to endure the pain caused by the affected limb (finger) from the emergency department visit after injury to surgery. The purpose of this study was to observe the analgesic effect and adverse reactions of different doses of dezocine in emergency hand trauma, and to provide evidence for analgesia in patients with emergency hand trauma.

Case 1, male, 3 years 11 months. He complained of varus deformity of his right foot and walking weakness, which gradually worsened for 16 months. He was admitted to hospital on June 25, 2014. In August 2012, the child suffered from severe hand-foot-mouth disease encephalitis with high fever and repeated convulsions and was hospitalized in the intensive care unit of Nanjing Children's Hospital affiliated to Nanjing Medical University. The foot horseshoe varus deformity appeared about 6 months after discharge, which gradually worsened. No clubfoot manifestations at birth, excluding congenital clubfoot. Physical examination: The right foot is in the shape of inverted horseshoe, the forefoot is adducted, the gastrocnemius muscle of the right calf is atrophied compared with the left side, and the muscle elasticity is poor. Electromyographic examination after admission showed electromyographic changes of neurogenic lesion, mainly involving right L4-S1, and mildly affecting L2-L3 innervated part of the examined muscle. Preoperative total spinal cord MRI: No obvious abnormal signals were found. Right Achilles tendon lengthening and external tibialis anterior muscle placement were performed after perfect preoperative preparation. Reviewing the medical records of acute phase of hand-foot-mouth disease in August 2012, the pathogenic examination of stool specimens and throat swab specimens of children was positive for EV-71. The clinical manifestations were skin rash and febrile convulsions with confusion. Physical examination: positive meningeal irritation sign. Cerebrospinal fluid bacterial smear and culture were negative, and the number of cells was 75×10⁶/L, predominantly monocytes; Protein increased, sugar and chloride normal. MRI examination of the head and whole spinal cord was performed 1 week after neurological symptoms in the children. MRI showed that T could be seen at the medulla-pontin junction₂Symmetry point-like length T visible on WI₁Long T₂Abnormal signal shadow, clear boundary. There was no obvious thickening of the spinal cord and no obvious abnormality in shape. Thoracic 11 – 12 level spinal cord length T₂Signal (on the right). Consider inflammatory changes of spinal myeloid. Lumbar puncture at discharge showed normal cerebrospinal fluid smear, culture and cell morphology (Figure 1，Figure 2，Figure 3，Figure 4，Figure 5，Figure 6)。

There are about 185 million hepatitis C virus (HCV) infected people worldwide, of which about 350,000 die every year from complications related to HCV infection, and about 1/3 of the patients will develop liver cirrhosis or liver cancer, thus greatly increasing the mortality rate^[1,2]。 The standard treatment in the past was pegylated IFN-α (PegIFN) combined with ribavirin (RBV). The sustained viral response (SVR) rate of this therapy was 40% ~70%, and the efficacy for genotype 1 was not good. direct – acting antiviral agents (DAAs) increase SVR rates to 90%^[1]。 However, drug resistance is an important factor affecting the efficacy of DAAs. In this paper, the characteristics of drug resistance, pre-existing drug resistance and how to deal with drug resistance of DAAs are reviewed.

In recent years, with the progress of spinal fixation surgery, the development of instruments and materials, the integration of imaging technology and the emergence of 3D printing technology, the craniocervical junction fixation technology has also made great progress. Because the craniocervical junction area involves complex structures and many skeletal abnormalities, it is difficult to unify the treatment plan. In this paper, the evolution and development of various craniocervical junction fixation techniques are summarized to provide reference for clinical decision-making.

Skeleton is one of the common metastatic sites of malignant tumors. Bone disease caused by tumor metastasis is a dynamic process in which tumor cells interact with multiple cells in the bone microenvironment^[1]。 The expression of tumor cell genes is regulated by growth factors and chemokines in the bone microenvironment. Bone metastasis lesions can be divided into osteogenic, osteolytic and mixed lesions^[2]The type of lesion depends on the balance between osteoblast-mediated bone deposition and osteoclast-mediated lysis-resorption. Tumor cells and tumor bone microenvironment can release a variety of factors that directly or indirectly affect osteoblast and osteoclast generation and metabolism^[3]。