2018年 · 第98卷第19期

In recent years, meta-evidence from people with genetic risk and elderly people with normal clinical cognition has shown that the occurrence of Alzheimer's disease (AD) is a continuous pathological process that began years before the clinical diagnosis of dementia^[1]。 Due to the repeated failure of clinical trials of new drugs for the dementia stage of AD, researchers have gradually realized that the focus of AD research should shift to the pre-dementia stage of AD.

Dementia has become one of the leading diseases causing death and disability in the elderly, and Alzheimer's disease (AD) is the leading cause of dementia. According to the China Cognition and Aging Study (COAST Study), as of 2009, there were 9.2 million dementia patients in China, of which 62.5% were caused by AD^[1]。 The disability rate of AD is high, patients lose the ability to live independently in the late stage, and need to be taken care of by others completely, which brings a heavy economic burden and nursing burden to society and family. At present, AD still lacks drugs that can change the course of the disease, and symptomatic treatment is still the main treatment. Therefore, clarifying the risk factors of AD and carrying out early intervention and prevention against these risk factors is one of the feasible methods to reduce or delay the onset of AD.

A 57-year-old male patient came to our hospital on 19 April 2013 due to gross hematuria for 1 week. Physical examination on admission: clear consciousness and good spirits, no yellowing staining of skin and sclera, no swelling of both lower limbs, heart and lungs (-), liver and spleen under the costs, flat and soft abdomen without tenderness and rebound pain, bilateral percussion pain in the kidney area (-), no abnormality in ureteral pathway, percussion pain in the bladder area (-), NS (-), and improvement in hematuria.

A 37-year-old married male was admitted to the hospital for "numbness of the left lower limb for more than 2 years, numbness of the right lower limb for 16 months, repeated headache with fever for 14 months, and double vision for more than 2 months". The patient developed left toe numbness without obvious trigger in June 2015, and no special treatment was given. The symptoms resolved by the end of 2015. In March 2016, there was no obvious trigger for back pain, which was persistent tingling and severe. The local hospital performed "acupuncture" treatment, and the pain improved, but numbness and weakness of the right lower limb gradually appeared, mainly numbness of the right calf and right foot, which gradually worsened. In April, walking was unstable, consciously stepping on empty feelings, easy to fall, and it was difficult to squat down and stand up; The weakness of lower limbs is aggravated after movement and can be relieved after rest. The local hospital considers "spinal vascular disease is not excluded" and gives treatment such as nutrition of nerves and improvement of circulation (details are unknown), and the symptoms are slightly relieved. In May 2016, the patient developed headache, which was swelling and pain in the right temporal roof, which was tolerable, lasting for about 1 h each time, several times a day to once a few days, and was relieved by self-administration of ibuprofen, sometimes accompanied by nausea and low fever, with a body temperature of 37~37.5 ℃. On June 14, 2016, he went to the Department of Neurology, PLA General Hospital, and underwent lumbar puncture examination. The cerebrospinal fluid white blood cells were 12×10⁶/L, albumin 619.9 mg/L, lumbosacral nerve root magnetic resonance showed cauda equina and lumbosacral nerve plexus changes (Figure 1), consistent with lumbosacral radiculitis, electromyography showed neurogenic damage of both lower limbs, and lung CT showed multiple small nodules in both lungs, which were considered benign. The diagnosis of lumbosacral nerve root damage and non-specific lumbosacral radiculitis was not excluded. Dexamethasone 20 mg, once/d, was given for 15 days. The weakness of the right lower limb was improved, the numbness was significantly reduced, and he was basically able to walk normally. After discharge, he was changed to oral prednisone tablets 60 mg, gradually reduced to stop, and took it for 1 month.

A 56-year-old female patient underwent maxillary mass resection and radical maxillary sinus resection in the Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jining Medical College in May 2017 due to upper palatal mass for 3 years. The postoperative pathological diagnosis was (maxillary) mesenchymal tumor, and then she was admitted to the Department of Neurology of Jining Medical College in July 2017 due to headache and right eyelid ptosis for 10 days. The headache was mainly on the right half of the head, which was paroxysmal and severe, without nausea, vomiting, limb twitching and unconsciousness. Physical examination: symptoms of right oculomotor nerve paralysis, local defect of left maxilla, normal muscle strength and muscle tone of limbs, bilateral Pap sign not drawn out, no abnormalities in sensory examination, stable and accurate fingers and noses of both fingers. Admitted brain MRI plain scan plus enhancement showed: right parasellar space-occupying lesion, considering the possibility of meningioma, atypical dura cavernous hemangioma to be discharged (Figure 1)； Whole brain angiography showed no obvious vascular abnormalities, so he was transferred to the neurosurgery department and underwent "right parasellar space-occupying microresection with right infratemporal keyhole approach" under combined intravenous and inhalation anesthesia. During the operation, the dura mater bulge of the lateral wall of the cavernous sinus at the floor of the middle cranial fossa was seen, and the texture was tough at touch. The lateral wall of the cavernous sinus was incised, and the tumor was found to be tough in texture and abundant in blood supply, about 2 cm ×3 cm ×3 cm. Postoperative pathology confirmed a (intra-cavernous sinus) mesenchymal tumor, considered sclerosing epithelioid fibrosarcoma (SEF,Figure 2)。

Rheumatic immune diseases are mostly systemic autoimmune diseases, which can lead to severe joint deformities, pain and dysfunction when involving the hip/knee joint, and often require total hip or total knee arthroplasty (THA/TKA). THA/TKA success focuses on optimizing perioperative management^[1]To improve the surgical effect and safety, reduce the surgical risk and increase patient satisfaction, so as to achieve the goal of rapid recovery. Rheumatic immune diseases mostly require long-term use of immunosuppressants, and the risks of perioperative infection, dislocation, rehospitalization rate and recurrence of disease activities are higher^[2,3,4]； At present, the concept of "long-term management and standard treatment" of diseases has gradually penetrated into the diagnosis and treatment of various rheumatic immune diseases. The perioperative management of anti-rheumatic drugs is a thorny problem faced by orthopedic surgeons in clinical activities. The American Rheumatology Association (ACR) and the American Association of Hip/Knee Physicians (AAHKS) jointly issued the "Guidelines for the Management of Perioperative Antirheumatic Drugs for Elective Total Hip/Knee Arthroplasty in Patients with Rheumatic Diseases" at the end of June 2017^[5](hereinafter referred to as the Guide). Now, the contents of the Guidelines on the perioperative management of antirheumatic drugs are briefly summarized and summarized as a reference for clinical practice.

Adenylate-activated protein kinase (AMPK) is a serine/threonine protein kinase widely existing in eukaryotic organisms. Its molecular structure is a heterotrimeric protein composed of three subunits: α, β and γ. The α subunit is composed of two subunits: α 1 and α 2, the β subunit is composed of two subunits: β 1 and β 2, and the γ subunit is composed of three subunits: γ 1, γ 2 and γ 3. The α subunit is its catalytic isomer. The β and γ subunits play an important role in maintaining the stability and the specificity of the substrate. In eukaryotic cells, AMPK plays an important role in regulating cellular energy balance, and its activation is mainly regulated by intracellular AMP/ATP. Any factors that lead to the increase of AMP/ATP, such as increased metabolites, oxidative stress, ischemia and hypoxia, can cause the activation of AMPK. In mammals, calcium/calmodulin-dependent protein kinase kinase (CaMKKb) and liver kinase B1 (LKB1) are two upstream kinases of AMPK. In addition, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) is currently recognized as an AMPK activator. AICAR can be taken up by cells and form monophosphate derivatives (ZMP) under the phosphorylation of adenosine kinase. ZMP has an AMP-like effect and can activate AMPK, and positively regulate signaling pathways that supplement ATP supply to cells, such as fatty acid oxidation, glucose transport, glycolysis and autophagy, and negatively regulate biosynthetic processes that consume ATP, including gluconeogenesis, lipid and protein synthesis. In addition, it can also regulate metabolism transcriptionally by directly phosphorylating a series of enzymes in these processes, or phosphorylating transcription factors, co-activators and co-inhibitors. AMPK can also act as an important regulator of aging by interacting with rapamycin target proteins (mTOR) and deacetylases (sirtuins) in many species^[1]。

In the past 20 years, with the development of molecular biology and the progress of gene sequencing technology, lung cancer treatment has developed from the traditional treatment model based on clinical features and pathological typing to the precise treatment model based on genotyping. However, the in-depth exploration of the mechanism of human immunity and the interaction between tumor and human immunity makes immunotherapy obtain good results in many tumor species. The treatment of advanced lung cancer is no longer the traditional single chemotherapy, but has entered the era of precision treatment with chemotherapy, targeted therapy and immunotherapy, as well as the combination of multiple methods. Previous studies on biomarkers to predict the efficacy of chemotherapy have failed to achieve the purpose of predicting or screening people suitable for a certain chemotherapy drug population, and the emergence of new detection methods such as second-generation sequencing (NGS) technology has pointed out the accurate selection of targeted therapy and immunotherapy direction.

Depression is one of the common mental illnesses, and somatic illnesses are often accompanied by depressive symptoms. The characteristics of depression such as high suicide rate, high self-harm rate and high recurrence rate show that depression is a serious social health problem. According to the World Health Organization report, as of 2012, there are estimated to be more than 350 million people with depression worldwide. Year 2014NatureThe epidemiological data released on China shows that the prevalence of depression in China is 3.02%^[1]。 Today's fast-paced, high-stress lifestyle makes depression a high-incidence disease with an increasing incidence year by year. The core clinical symptoms of depression mainly include: (1) "three lows"-low mood, slow thinking and decreased voluntary activity; (2) Psychological symptoms: "three noes"-helplessness, hopelessness and uselessness; (3) "Three Selves"-inferiority, suicide and self-crime; (4) Physical symptoms: sleep disorders, fatigue, weight loss, decreased appetite, decreased sexual desire, constipation, pain, and discomfort. The complaint involves autonomic dysfunction; (5) Other symptoms: depersonalization, disintegration of reality, obsessive-compulsive symptoms^[2]。 Failure to intervene in time will lead to the aggravation of the disease and enter a vicious circle, resulting in high suicide rate and high self-harm rate, bringing heavy burden and serious losses to patients, families and society.

Cervical cancer is the fourth most common malignant tumor in women worldwide, with 85% occurring in developing countries. It is the second leading cause of cancer death among women in developing countries after breast cancer^[1]。 It is estimated that there were 528,000 new cases of cervical cancer and 266,000 deaths worldwide in 2012^[2]。 The incidence of cervical cancer in China is also rising, with 98,900 new cases and 30,500 deaths in 2015^[3]。 According to the guidelines of the National Comprehensive Cancer Network (NCCN), radical cervical cancer surgery (also known as extensive total hysterectomy, RH) and systemic lymphectomy are standard protocols for the treatment of early cervical cancer^[4]。 Different types of RH need to remove a certain range of parauterine tissue to achieve thoroughness of tumor resection. A large number of pelvic nerves are distributed in the parauterine tissues, and RH operation is bound to destroy these nerve tissues, resulting in postoperative bladder, rectal and sexual dysfunction, among which bladder dysfunction is the most common. The incidences of dysuria, stress incontinence, urgency incontinence, frequency and urgency after RH were 36%-47%, 20%-76%, 8%-45%, 23% and 19%, respectively^[5]。 The associated urinary symptoms are the most common complications of surgical treatment of cervical cancer and severely disrupt the quality of life of cancer survivors. Pelvic nerve-preserving radical cervical cancer surgery (NSRH) has become one of the standard procedures for cervical cancer treatment by preserving the autonomic nerves that innervate the bladder to reduce the incidence of bladder dysfunction in patients. In different reports, the proportions of urinary dysfunction after NSRH and RH were 5.4% ~33.3% and 11.3% ~100%, respectively^[6,7,8,9]。 This article discusses and summarizes the neuroanatomy, surgical safety and surgical techniques related to NSRH, and the effects of surgery on organ function, quality of life and survival outcome of patients.