Volume 98  ·  Issue 35  ·  2018

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection^[1]。 After decades of exploration, the mortality rate of sepsis has dropped to about 20%^[2,3]。 Although tremendous advances have been made in the treatment of sepsis, its pathogenesis remains unclear. In recent years, suppression of host immune function after infection has been considered to be a very important link in the pathogenesis of sepsis. Many studies have also proved that reversing immune suppression can further reduce the mortality of sepsis^[4]。 This article will start from the identification of sepsis immunosuppressed patients and the selection of immunomodulatory drugs, aiming to help clinicians better identify sepsis immunosuppressed patients and carry out possible immunomodulatory therapy.

It has been recognized that recovery of the microcirculation is not fully guaranteed after the correction of the macrocirculation during shock resuscitation. Recently, some scholars have put forward the concepts of "microcirculation shock", "microcirculation failure" and "microcirculation resuscitation", and the shock resuscitation has gone deep into the microcirculation level. In clinical work, there is no consensus on how to realize shock resuscitation from macrocirculation to microcirculation, and how to interpret the relationship between macrocirculation and microcirculation is still a major challenge. On the one hand, macrocirculation is the cornerstone of microcirculation resuscitation. Many clinical interventions (such as volume expansion, vasoconstricting active drugs, cardiotonic drugs, etc.) need to affect microcirculation by acting on macrocirculation. At this time, we should avoid breaking away from macrocirculation and talking about microcirculation resuscitation, and avoid over-emphasizing the direct effect of clinical intervention on microcirculation. On the other hand, the endpoint of shock resuscitation is to restore cellular oxygen metabolism and organ function, while microcirculation acts as a bridge between macrocirculation and cells. If the coupling relationship between macrocirculation and microcirculation is not correctly understood, only the target of macrocirculation is used as a guide and the response of microcirculation is ignored, which can lead to clinical treatment deviation. Sometimes, although normal macrocirculation indicators are apparently maintained, it may not be beneficial to microcirculation. For example, the purpose of shock resuscitation expansion is to increase cardiac output, and the further goal is to improve microcirculation perfusion. However, if microcirculation loses its regulatory response to macrocirculation, even if cardiac output is increased, microcirculation perfusion cannot be increased accordingly, but instead, it will bring potential damage of volume overload.

acute respiratory distress syndrome (ARDS) is a common acute respiratory failure in the Department of Critical Care Medicine (ICU), accounting for 10% of ICU patients. Although the basic and clinical research on ARDS has been deepened, and the treatment measures such as lung protective ventilation have been implemented, the mortality rate of ARDS is still as high as 35% ~46%^[1]。 There has been no breakthrough in the etiology and specific treatment of ARDS, and the treatment is mainly in the organ support level such as mechanical ventilation. In recent years, the understanding and clinical diagnosis and treatment strategies of ARDS have made some progress, which is described in this article.

Analgesia and sedation is one of the basic treatments for patients in intensive care unit (ICU), and this concept has been recognized by many critical care workers. However, in clinical practice, different implementation strategies and clinical efficacy often cause confusion, such as the depth of degree, the timing, the length of time and the trade-off of advantages and disadvantages. The author has taken the lead in emphasizing that analgesia and sedation is the basic treatment for critically ill patients in ICU in China in recent 20 years, and has successively put forward and explained many concepts such as "no monitoring, no analgesia and sedation" and "the goal is not equal to the goal"^[1,2,3]。 The so-called purpose refers to the place or result of the ultimate intended achievement of the behavior, and the goal is the sign in the process of approaching the purpose. The target can indicate the distance and direction between the location and the destination, and the destination is the end point of a series of targets. Therefore, in clinical treatment, the purpose is always the same, while the goal may be multiple and vary.

Continuous blood purification (CBP), also known as continuous renal replacement therapy (CRRT), is a commonly used treatment technique for critically ill patients. Volume management, or fluid management, is the focus and difficulty of CBP treatment. This is determined by the narrowing of the tolerance interval for volume in critically ill patients; There are difficulties in accurate evaluation of cardiac preload in patients; Volume management in critically ill patients presents different characteristics at different stages of the disease course; During CBP, the patient has a large amount of fluid in and out, etc. The 2016 Acute Disease Quality Initiative (ADQI) consensus laid out the precision CRRT philosophy, which includes principles for achieving precision fluid management, but does not provide a specific approach with clinical actionability^[1]。 Aiming at this difficulty, we propose and practice the target-guided capacity management (GDVM) strategy of CBP. Through good medical and nursing cooperation, GDVM can dynamically set, titrate and adjust the liquid balance target and volume safety value, which can achieve accurate liquid management during CBP. GDVM is helpful to improve the quality of CBP and improve the prognosis of patients. At the same time, it has good clinical operability and is worthy of promotion.

In critically ill patients, abnormal coagulation mechanism is common, and hemorrhage or thrombosis affect the prognosis. Coagulation abnormalities vary in degree, from simple laboratory parameter abnormalities to disseminated intravascular coagulation (DIC), and DIC, as an independent predictor of mortality risk in critically ill patients, is the most concerned issue for clinicians. DIC is an acquired clinical syndrome caused by a variety of etiologies (such as infections, traumas, tumors, obstetric accidents, etc.), characterized by activation and loss of localization of intravascular coagulation, which can lead to microvascular damage and trigger organ dysfunction. Sepsis, trauma, or major surgery are common causes of DIC^[1]。 It is worth noting that not all coagulation dysfunction induced by sepsis, trauma or other injury factors are manifested as DIC. For example, some cases of sepsis-associated coagulopathy (SIC) and traumatic shock acute coagulopathy (ACOTS) only show thrombocytopenia, prolonged prothrombin time (PT) or increased international standardized ratio (INR), but do not reach the dominant DIC diagnostic score, and their impact on prognosis and diagnosis and treatment strategies are different from those of DIC. This article will review the mechanism, common manifestations and principles of diagnosis and treatment of coagulation disorders in critically ill patients.

The development of drug clinical trials in China is increasing day by day, and relevant ethical norms and review methods are also being continuously improved in implementation, playing a major guiding role in practice. For issues not covered by domestic norms, you can refer to international ethical conventions and progress interpretation. Ethical review is usually carried out from seven aspects: scientific design and implementation of the study, informed consent, assessment of risks and benefits, subject recruitment, medical treatment and protection of subjects, privacy and confidentiality, and protection of vulnerable groups^[1]The important purpose is to protect the basic rights and interests of subjects.

Duchenne muscular dystrophy (DMD) is a treatable X-linked recessive inherited myopathy caused by pathogenic variation of dystrophin gene. Its causative gene is abbreviated as DMD gene. The incidence of the disease is 1/5 000 (1/3 599 to 1/9 337) in surviving male infants^[1,2,3,4]1/4 560 in Mainland China^[5]。 The pathogenic variation of DMD gene caused the abnormal expression of various anti-dystrophin subtypes. The negative expression or significant decrease of muscle subtypes led to the occurrence and development of muscular dystrophy. The abnormal expression of various subtypes expressed in brain tissue, myocardium, retina, kidney, peripheral nerve and other tissues^[6,7,8,9]As a result, some patients are also accompanied by the involvement of other organ systems, including cognitive impairment, behavioral disorders, digestive dysfunction, and cardiomyopathy.^[10,11]。 Multidisciplinary assessment and corresponding comprehensive management of patients' multi-system damage can prolong the independent walking time and survival time of DMD patients, and improve the quality of life of patients^[12]。 The therapeutic effect of DMD is the cumulative effect of various methods, which requires the knowledge and cooperation of patients and nurses to maximize the therapeutic effect. Therefore, the experts in pediatrics, neurology, respiratory medicine, cardiology, orthopedics/spine surgery and rehabilitation medicine of this cooperative group jointly formulated the DMD management consensus in China and assisted provinces and cities to establish DMD medical consortium management plans.

Radioactive seed implantation has become one of the standard treatments for early prostate cancer. American Cancer Society, Society of Urology, Society of Clinical Oncology, Society of Radiation Oncology, Society of Close, and NCCN guidelines are all promoted as standards^[1,2,3]。 Prostate cancer seed implantation is assisted by transrectal ultrasound guidance combined with pubic template to realize the rational distribution of particles in the three-dimensional space of the prostate, so as to ensure that the seed implantation treatment is completely consistent with the preoperative plan.

To investigate whether killer cell immunoglobulin-like receptor 3DS1(KIR3DS1)and Bw4^80Ile could play a protective role during HIV-1 infection.

KIR3DL1/3DS1 and Bw4, Bw6 were genotyped by SSP-PCR and Bw4 allotypes (Bw4^80Ile and Bw4^80Thr)were classified via sequencing among 109 individuals acutely infected with HIV-1 in Beijing You′an Hospital between 2006 and 2012.

(1)Of the 109 patients, 65, 7, and 37 subjects respectively harbored KIR3DL1/KIR3DL1, KIR3DS1/KIR3DS1, and KIR3DL1/KIR3DS1 genotypes. Their viral set points were determined as 4.35±0.79, 4.24±0.49 and 3.99±0.85 respectively. The viral set point of patients carrying KIR3DL1/KIR3DS1 was significantly lower than the KIR3DL1/KIR3DL1 genotype patients (P=0.032). (2)26, 41, 42 subjects harbored Bw4^80Ile, Bw4^80Thr, Bw6/6, respectively. Viral set points of these subjects were respectively 3.89±0.49, 4.20±1.03 and 4.44±0.59.One-way ANOVA indicated that Bw4^80Ileinfluenced the levels of viral set point(P=0.027). Moreover, the level of viral set point of the Bw4^80Ile genotype was significantly lower than the Bw6/6 genotype (P=0.020). These outcomes indicated Bw4^80Ile was associated with lower levels of viral set point.(3)Viral set point of patients harboring KIR3DS1 and Bw4^80Ilewas 3.26±0.81 and significantly lower than individuals possessing other genotypes (all P<0.05). KIR3DS1 and Bw4^80Ile conferred an advantage over other genotypes, especially over KIR3DS1 and Bw6/6 (P=0.006), KIR3DL1 and Bw6/6 (P=0.015) and even KIR3DL1 and Bw4^80Ile (P=0.019 6) in delaying CD4 count decline within 3 years after HIV-1 infection.

KIR3DS1 and Bw4^80Ile are synergistically related to lower viral set point and slowing down the CD4 count decline as Bw4^80Ile in the presence of KIR3DS1.

To explore the clinical characteristics of cryptococcus bloodstream infection.

A retrospectively analysis was performed by collecting data of clinical manifestations, underlying diseases, susceptible factors, therapy and prognosis of cryptococcus bloodstream infection in the First Affiliated Hospital of Soochow University from December 2006 to December 2017.

The most common symptom of the 16 patients was fever (12/16). When combined with cryptococcus infection of central nervous system, the manifestations may include dizziness, headache, nausea and vomiting.Among the 16 patients, 11 cases had underlying diseases, which listed as leukemia, lymphoma, diabetes mellitus, hepatitis B, cirrhosis, chronic kidney disease and carcinoma of the liver; 12 cases had invasive procedures, 6 cases had hypoproteinemia, 4 cases had long-term usage of glucocorticoids, and 5 cases received broad spectrum antibiotics longer than 1 week.8 cases died, 6 cases improved and 2 cases were transferred to the specialized hospital for their newly diagnosed AIDS.

Bloodstream infection of cryptococcus is a relatively rare disease.Fever is one of the most common symptoms of cryptococcus bloodstream infection.Underlying diseases, invasive procedures, hypoproteinemia, long-term application of glucocorticoids and antibiotics are the risk factors for cryptococcus bloodstream infection.

To investigate the effect of progesterone on estrogen receptor(ER), progesterone receptor(PR), proliferating cell nuclear antigen (PCNA) , bcl-2 , c-myc, c-fos, and epidermal growth factor receptor(EGFR) expression in normal human breast tissues implanted into nude mice.

A xenograft-model, pieces of normal human breast tissue implanted subcutaneously into 9-10-week-old athymic nude mice, was established.The tissue of each case was divided into 4 parts, and were transplanted into 4 nude mice.These mice were randomly divided into 4 groups, namely control group: normal saline 0.1 ml; estrogen group: estradiol benzoate 20 μg (0.1 ml, 1 mg/kg); progesterone group: 60 μg (0.1 ml, 3 mg/kg); estrogen plus progestin group: estradiol benzoate 20 μg (0.1 ml, 1 mg/kg) and progesterone (0.1 ml, 3 mg/kg) 60 μg.Treatment was given every other day, and human breast tissues were removed for experiments after treatment for 4 weeks.The implanted breast tissue were fixed and sliced.The expression of ER, PR PCNA and bcl-2 were assayed by immunohistochemical, c-myc, c-fos, and EGFR mRNAs were determined by in situ hybridization.

In estrogen group, and estrogen plus progestin group, the positive expression of ER was lower and PR was higher than those of the control group (P<0.05); the expression of ER and PR in progesterone group had no differences compared with the control group (P>0.05); the expression of PCNA and bcl-2 in estrogen group were higher than that of the control group (P<0.01,P<0.05), while they showed no significant difference in the other two drug groups compared with the control group (P>0.05). The expression of c-myc, c-fos and EGFR in estrogen group and estrogen plus progestin group were higher than those in control group (P<0.01). The expression of c-myc in the progesterone group was higher than that in the control group (P<0.01), and the expression of c-fos and EGFR in the estrogen and progesterone groups were not significantly different compared with those in the control group (P>0.05).

Progesterone did not affect the proliferation and apoptosis of human normal breast tissue, but may have anti-proliferative and pro-apoptosis effects when coupled with estrogen.And it can up-regulate the expression of c-myc.

To evaluate the prognosis and complications after reduction of monochorionic multifetal pregnancies using bipolar umbilical cord coagulation (BCC) or radiofrequency ablation (RFA).

A literature search were performed by using online databases including PubMed, Embase, and COCHRANE.The publications that described prognosis and complications after selective reduction of monochorionic twin pregnancies using either BCC or RFA for studies with clear outcome data were identified.

We identified five retrospective cohort studies for the meta-analysis and 231 cases of BCC and 174 cases of RFA.There was no statistical difference in overall survival after reduction between BCC group (79.2%) and RFA groups (76.4%) (RR=0.96; 95%CI: 0.86~1.08; P=0.48). Neonatal mortality was similar in both groups (8.2% vs 11.1%, respectively; RR=1.34; 95%CI: 0.60~2.99; P=0.48). However, intrauterine fetal death (IUFD) in the RFA group was 13.6%, and it significantly higher than that in the BCC group 7.7% (RR=2.15; 95%CI: 1.10~4.21; P=0.03). In contrast, after reduction, those in the RFA group had less preterm premature rupture of membranes (PPROM) compared with the BCC group (17.1% vs 27.5%, RR=0.58; 95%CI: 0.39~0.86; P=0.007).

RFA and BCC groups have similar overall survival for complicated monochromic multiple pregnancies, but RFA was more prone to IUFD, and BCC tended to have more PPROM.Thus, procedures should be chosen according to specific clinical situations and pregnancy conditions.

Anti-SRP (signal recognition particle, SRP) antibody positive myopathy, also known as myopathy with antibody to the signal recognition particle, according to the classification criteria of idiopathic inflammatory myopathy proposed by the European Center for Neuromuscular Diseases and the American Collaborative Group for myopathy Research in 2004^[1]The disease belongs to immune-mediated necrotizing myopathy (IMNM). The main clinical manifestations are progressive limb weakness and muscle atrophy, mainly at the proximal ends of the limbs, may be accompanied by cervical flexor weakness, dysphagia and respiratory insufficiency, less facial and heart involvement, and more heart involvement has been reported in the past^[2,3]Concomitant symptoms such as muscle soreness or muscle spasm may also occur. Serum creatine kinase was significantly elevated in laboratory, and most of the electromyography showed myogenic lesions. The muscle MRI may show diffuse edema of the affected muscles. Skeletal muscle pathology showed necrosis and regeneration of muscle fibers with no or little infiltration of inflammatory cells^[4,5]。 At present, there are still few reports of this disease in China, and there are no reports of cases with obvious inflammatory cell infiltration. This study reported the relevant data of 3 patients with anti-SRP antibody positive myopathy to explore the clinical and pathological characteristics of the disease.

A 65-year-old male patient had repeated cough, sputum and fever for half a year, and the right hilum was found to occupy space for 2 months. Six months ago, the patient began to have cough and sputum, which was yellow purulent sputum with moderate amount and fever. After anti-infective treatment in the community hospital, it improved, but the condition was repeated. Have a smoking habit for more than 40 years, 20 cigarettes/d. Chest CT plain scan + enhanced scan of Drum Tower Hospital affiliated to Nanjing University School of Medicine showed bronchial occlusion in the middle lobe of the right lung, consolidation in the middle lobe of the right lung, and a soft tissue density mass shadow, 4.8 cm ×3.2 cm in size, with striped high density shadow, unevenness on enhanced scan, and multiple small lymph nodes in the mediastinum (Figure 1)。 Bronchoscopy revealed that a bulging lesion occluded the lumen at the bronchial opening of the middle lobe of the right lung, the surface mucosa was smooth, and a small amount of yellow purulent sputum was seen in the trachea (Figure 2)； No malignant tumor cells were found in the right middle lung brush; The bronchial mucosa tissue submitted for examination showed chronic inflammation with squamous epithelial metaplasia and hyperplasia (Figure 3)。 No special abnormalities were found in the remaining auxiliary examinations. Clinically misdiagnosed as central lung cancer of the right lung, thoracoscopic assisted right middle and lower lobe resection + lymph node dissection was performed under general anesthesia. The resected tissue showed gray-white mass growing close to the hilar and in the middle lobe bronchus, with a size of 2.0 cm ×1.0 cm ×1.0 cm, and the section was gray-white, solid and medium. After 6 days of hospitalization, no postoperative complications were observed. Chest X-ray examination after 2 weeks of discharge showed good recovery. Histopathology showed bronchial mesenchymal hamartoma with myeloid metaplasia, fibrous tissue hyperplasia, bronchial mucosal metaplasia, acute and chronic inflammatory cell infiltration, small airway and vasodilation, bronchial margin showed chronic inflammatory cell infiltration under mucosa, lymph node reactive hyperplasia (Figure 4)。

Acute respiratory distress syndrome (ARDS) is an important cause of acute respiratory failure, with a mortality rate of up to 40%^[1]。 Autophagy of alveolar epithelial cells plays an important role in the development of ARDS^[2,3]。 Studies have shown that autophagy confined to alveolar epithelial cells can alleviate ARDS lung injury, but uncontrolled autophagy of alveolar epithelial cells may lead to aggravation of ARDS lung injury, and the degree of autophagy of alveolar epithelial cells is closely related to ARDS lung injury.

Prostate cancer is one of the most common malignant tumors in men. In the United States, the incidence of prostate cancer ranks first among male malignant tumors, and the mortality rate ranks second^[1]。 Although the incidence of prostate cancer in China is lower than that in Europe and the United States, it has continued to rise in recent years. The National Cancer Center estimates that 60,300 new cases of prostate cancer in China will occur in 2015, accounting for the sixth place in male malignant tumors^[2]。 The traditional treatment of prostate cancer is comprehensive treatment based on surgery, while endocrine therapy is the first-line treatment for middle and advanced prostate cancer, but after 14 to 30 months of treatment, it will still develop into metastatic castration-resistant prostate cancer (mCRPC)^[3]。 Current treatments for mCRPC include docetaxel and cabazitaxel chemotherapy^[4,5], abiraterone and enzalutamide targeted therapy^[6,7]But they will produce more adverse reactions. Immunotherapy for prostate cancer is a new therapeutic method, which can kill tumor cells by regulating the immune system, and has a good clinical prospect^[8,9]。 chimeric antigen receptor-T (CAR-T) cell therapy, as one of the most promising immunotherapy, has achieved good efficacy in the treatment of hematological malignant tumors and brain malignant glioma, and most cases have been completely remitted (complete response, CR)^{[10,11,12,13,14,15,16]}。 This article reviews the current status and curative effect of CAR-T cell therapy.

Tumor therapeutic electric fields (TTFields) are a kind of medium frequency and low intensity electric fields, which can effectively block the process of cell division and interfere with organelle synthesis^[1]。 This novel therapeutic modality has shown strong potential in a variety of tumor types. The results of a phase 3 clinical trial showed that there was no significant difference in progression-free survival (PFS) and overall survival (OS) in patients with glioblastoma compared with standard temozolomide chemotherapy with TTFields treatment, and the incidence of systemic adverse reactions in patients was reduced^[2]。 This result led to the Food and Drug Administration's (FDA) approval of TTFields for clinical use. In this paper, the mechanism of action, basic research, clinical research, adverse reactions and application prospect of TTFields will be described in combination with the research progress at home and abroad.