Volume 98  ·  Issue 15  ·  2018

In recent years, critical care medicine has made rapid development. In July 2008, critical care medicine was approved by the state as a secondary discipline of clinical medicine. Some scholars simply equate traditional clinical thinking with critical clinical thinking, while ignoring the professional characteristics of critical care medicine. Clinical thinking of severe disease has its particularity and professionalism, which is different from traditional clinical medicine thinking to a certain extent. Therefore, while following the traditional medical clinical thinking mode, the characteristics and ways of critical clinical thinking are worth re-thinking and summarizing. Based on the Beijing Hemodynamics Consensus^[1]Combined with the clinical practice of critical care medicine, we further summarize and put forward the following ten ways and concepts of critical care clinical thinking.

Dementia is an acquired intelligence impairment syndrome with cognitive impairment as the core symptom. Cognitive impairment can involve cognitive domains such as memory, learning, language, execution, visual space, etc. The degree of impairment is enough to interfere with daily life ability or social occupational function. It is often accompanied by mental, behavioral and personality abnormalities at a certain stage of the disease course. Therefore, the assessment of such patients typically includes cognition, social and daily activity, and psychiatric behavioral symptoms, which can be summarized as ABC. Among them, the cognitive function assessment involves the above-mentioned plurality of cognitive domains.

Auxiliary examinations for cognitive impairment diseases include body fluid examination, imaging examination, electrophysiological examination and genetic testing. Selecting appropriate auxiliary examinations can effectively assist in the diagnosis and differential diagnosis of cognitive impairment diseases and monitor the disease progress.

Head and neck cancer accounts for 30% of malignant tumors in the whole body, and surgery is the main treatment. Radiotherapy combined with chemotherapy is mainly used when locally advanced or unable to be resected surgically. Local and regional recurrence after surgery and radiotherapy is still the main cause of failure, and there is no ideal method for salvage treatment after recurrence. Radioactive seed implantation has become one of the standard treatments for early prostate cancer^[1,2,3]。 Prostate cancer seed implantation treatment is transrectal ultrasound-guided combined with pudendal template assistance, which achieves a rational spatial distribution of particles in the prostate gland, which can ensure that the seed implantation treatment is completely consistent with the preoperative plan.

To evaluate the diagnostic value of two-dimensional shear wave elastography(2D-SWE)in the assessment of hepatic fibrosis in a large-scale clinical setting.

A total of 1 079 subjects who underwent partial hepatectomy were examined with 2D-SWE to measure liver stiffness before operation and the liver stiffness measurements were compared with histologic findings.The published cutoff values of liver stiffness examined with 2D-SWE were used as a reference, as 7.2, 9.2, and 10.4 kPa for diagnosing substantial fibrosis(S2), severe fibrosis(S3), and cirrhosis(S4), respectively.The area under curve(AUC)was calculated to verify the value of 2D-SWE in the evaluation of hepatic fibrosis.

Compared with the pathological diagnosis, the AUC of 2D-SWE in diagnosing substantial fibrosis(S2), severe fibrosis(S3), and cirrhosis(S4)were 0.976, 0.981, and 0.968, the sensitivity were 95.3%, 92.6%, and 93.5%, the specificity were 87.8%, 87.5% and 89.3%, and the accuracy were 88.8%, 90.0% and 91.0%, respectively(P<0.05).

2D-SWE is an effective imaging tool for noninvasive diagnosis of hepatic fibrosis.

To detect potential pathogens including pseudorabies virus in patients with encephalitis of unknown etiology in China and describe novel encephalitic entities.

Patients with clinically suspected infectious encephalitis were enrolled in a multicenter study to identify the pathogens in PUMCH Encephalitis Program.Next-generation sequencing(NGS) of cerebrospinal fluid (CSF) was used in patients with encephalitis of unknown etiology enrolled from 2016 to 2017.The patients diagnosed as PRV encephalitis were studied to describe this novel entity.

The four patients(3 male, 1 male, 38-54 years old) had occupational exposure to raw park when working in the production or marketing of pork and at least one got injured during pork-cutting.Two of them were confirmed with NGS of CSF, and anti-PRV antibodies were positive in 3 patients whose serum was available for serological analysis.They all presented with an acute onset of fever, convulsion, loss of consciousness and respiratory failure within 1 to 4 days and rapidly deteriorated even on extensive treatment.All the patients needed ICU admission and 3 needed mechanical ventilation.Two patients also had bilateral retinitis.Neuroimaging revealed symmetric gray matter lesions including limbic system, basal ganglia and midbrain without obvious hemorrhage.Lumbar puncture revealed elevated intracranial pressure and lymphocytic pleocytosis [(6-64)×10⁶/L] of CSF.The patients failed to response to the treatment of acyclovir combined with intravenous immunoglobulin and steroids.Modified Rankin Score was 3, 5, 5 and 6 (died) for the 4 patients respectively on last follow-up.

PRV could be a cause of severe encephalitis.The patients with suspected pseudorabies encephalitis (PRE) need to be tested for PRV DNA timely.Severe encephalitis with bilateral involvement of limbic system, basal ganglion, thalamus and midbrain in patient with occupational exposure indicate this emerging infectious encephalitis.

To assess the efficacy of Yisaipu tapering in patients with ankylosing spondylitis (AS).

A total of 87 cases of AS patients from Guangdong Second Provincial General Hospital who were treated with Yisaipu and celecoxib were retrospectively analyzed from February 2013 to April 2017.All patients received full dose Yisaipu and celecoxib in the initial 12 weeks.After that, the patients in the full dose group maintained Yisaipu (50 mg/w) treatment from the 13^rd to 24^th week, while tapering group received Yisaipu 50 mg subcutaneous injection once every other week.By using AS disease activity score (ASDAS), Bath AS functional index (BASFI) and magnetic resonance (MR) score of sacroiliac joint (SIJ) plus recording adverse events, differences of efficacy and safety between groups were compared.

ASDAS and BASFI of tapering group were 1.1±0.7 and 1.3±1.1, while those of full dose group were 1.0±0.7 and 1.1±1.0, respectively.No significant difference of ASDAS or BASFI was found between groups.Besides, the MR scores of tapering and full dose groups were 8±7 and 8±6 respectively before therapy, while they were significantly lower in the 24^th week (4±4 and 4±3, P<0.05). However, changes of MR score between groups were similar (P>0.05).

Dose tapering of Yisaipu subcutaneous injection might be effective for keeping stable of disease activity and function in patients with AS.Its efficacy is similar to those of full dose Yisaipu.

To evaluate the effect of promoting knee joint rehabilitation after total knee arthroplasty (TKA) with a rehabilitation training instrument NEO-GAIT.

Sixty patients who received TKA from January 2017 to July 2017 in the Third Hospital of Hebei Medical University were randomly assigned to receive rehabilitation training with continuous passive motion (CPM) or NEO-GAIT with random number (30 cases in CPM group, included 8 males and 22 females; 30 cases in NEO-GAIT group, included 6 males and 24 females). The visual analogue scale (VAS) evaluation of pain, the postoperative range of motion (ROM) of the knee at the 5th and 10th day, and the Hospital for Special Surgery Knee-rating Score (HSS) at 1-month and 3-month follow-up were recorded. The data were compared between the two groups with paired t test.

All the patients were followed-up for more than 3 months. The mean VAS in CPM group and NEO-GAIT group on the 5th day was 2.4±1.1, 2.8±1.3, respectively; and it was 2.1±1.1, 2.5±1.2 respectively on the 10th day after the operation (t=-1.618, -1.505, both P>0.05). There was no significant difference in ROM on the 5th day after operation between the 2 groups (84°±12° vs 85°±12°,t=-0.377, P>0.05); however, it was remarkably higher in the NEO-GAIT group (95°±11°) than that in CPM group (88°±8°) on the 10th day after the operation (t=-3.002, P<0.05). The HSS score at 1-month follow-up in CPM group was 72±9, and it was 84±10 in NEO-GAIT group (t=-5.358, P<0.05); but it was comparative between the two groups at the 3-month follow-up (87±5 vs 89±5,t=-1.575, P>0.05).

NEO-GAIT plays a more active and effective role in promoting postoperative rehabilitation after TKA than CPM.

To compare the neonatal and maternal outcomes between the patients with umbilical cord around the neck (≥3 loops) and with (1 or 2 loops).

A retrospective analysis was conducted on the clinical data of 160 cases with multiple umbilical cord around the neck (≥3 loops) in the Department of Obstetrics, Women′s Hospital School of Medicine Zhejiang University between January 2014 and April 2017.For each case, two control women who gave birth at the same day with vertex position and singletons were selected.The neonatal and maternal outcomes were compared.

(1) The incidence of cord multiple cord around the neck (≥3 loops) in our hospital was 0.45%. (2) Comparison between groups: The rate of abnormal fetal movement or abnormal cardiotocography in case group was higher than those of the control group, (33.13%, 53/160) vs (8.13%, 26/320), with significant difference, P=0.000.The Umbilical Artery Systolic/diastolic (S/D) ratio of the case group was lower than that of the control group, 2.00(0.40) vs 2.14(0.40), with significant difference, P=0.000.The cesarean section rate of the case group was higher than that of the control group, (81.25%, 130/160) vs (7.50%, 24/320), and the difference was statistically significant, P=0.000.Birth Weight of the case group was lower than that of the control group, (3 143±367) g vs (3 323±349) g, with significant difference, P=0.000.(3) Comparison between subgroups: The rate of lateral incision or obstetrical forceps in the subgroup of virginal delivery among the case group (n=30) was higher than that in the control group (n=296), (30.00%, 9/30) vs (12.50%, 37/296), with significant difference, P=0.009.While, the Apgar score at 1 and 5 min of the virginal delivery case in the case group were lower than that in the control group, 10(1.25) vs 10(0) and 10(0) vs 10(0), there were both significant difference, P=0.000, 0.012, respectively.The rate of meconium-stained amniotic fluid, 1 min Apgar score of ≤7 and NICU admission were showed no significance, all P>0.05.(4) After Logistic regression, the four factors most closely associated with meconium-stained amniotic fluid in patients with multiple cord around the neck (≥3 loops), which were gestational age ≥39 weeks, Birth Weight >3 500 g, umbilical cord around the neck ≥4 loops, and trial of labor.

(1) Multiple umbilical cord around the neck (≥3 loops) had a more positive treatment. Vaginal delivery led to lower APGAR score, but didn′t increase the incidence of neonatal asphyxia.(2) Independent risk factors for meconium-stained amniotic fluid were gestational age ≥39 weeks, Birth Weight>3 500 g, umbilical cord around the neck ≥4 loops and trial of labor.

To study the relationship of serum lipoprotein-associated phospholipase A2 (Lp-PLA2) with vascular dementia (VD) after ischemic stroke.

A total of 226 ischemic stroke patients who visited the People′s Hospital of Zhengzhou University from June.2013 to Oct.2016 were included and divided into the VD group and the non-dementia group according to the degree of cognitive impairment.The non-dementia group were further divided into the normal cognition group and the vascular cognitive impairment no dementia(VCIND) group.The general information of all patients were collected and the serum Lp-PLA2, Hcy, hs-CRP and the blood lipid indexes were detected.The Logistic regression model was built to analyze the association of Lp-PLA2 with the VD, correlation analysis and ROC curve were conducted to analyze the correlation of Lp-PLA2 with the state of cognitive impairment and to generate the cutoff value respectively.

The serum Lp-PLA2 in VD group[(221±84) ng/ml] was significant higher than the non-dementia group[(133±60) ng/ml], the Lp-PLA2 in VCIND group[(148±65) ng/ml] was significant higher than the normal cognition group[(114±48) ng/ml](P<0.05). The result of Logistic regression showed that Lp-PLA2 was a significant risk factor of VD[(OR(95%CI)=1.015(1.010-1.021)], and its level was negatively correlated with the score of cognitive function.The cutoff value of Lp-PLA2 between the VD and non-dementia was 164.65 ng/ml and was 120.8 ng/ml between the normal cognition group and VCIND group.

Lp-PLA2 is a significant risk factor of VD after ischemic stroke.

To investigate the cerebral protective effect of shRNA down-regulated matrix metalloproteinase-9(MMP-9) on cerebral infarction rats.

32 SD rats were randomly divided into four groups (8 for each group): group A (sham operation group): the branches of external carotid artery were only separated and ligated and were not be inserted thread; group B (MCAO group): rat MCAO models were made referring to the conventional Longa method; group C (physiological saline group): rats were injected with 5 μl saline two weeks before MCAO models; group D (lentivirus intervention group): rats were injected with 5 μl lentivirus-mediated shRNA two weeks before MCAO models.The diffusion tensor imaging(DTI) was used to evaluate the tissue of cerebral ischemic of middle cerebral artery occlusion(MCAO) in rats.At 4, 8, 12, 18 and 24 h after MCAO, the ADC value and FA value of the lesion side were calculated.The expression of MMP-9 protein in brain tissue of ischemic side was measured by Western blot, and the expression of MMP-9 protein was observed by paraffin section and immunohistochemistry.SPSS 17.0 software was used for statistical processing, and the difference was statistically significant in P<0.05.

At 4, 8, 12, 18, 24 h after ischemia, the values of ADC and FA in the ischemic area of the lentivirus intervention group were higher than those in the MCAO group, and the difference was statistically significant (the t values of ADC values at different time points were 8.78, 3.30, 3.58, 4.55 and 13.12, respectively P<0.05.Thet values of FA values at different time points were 2.51, 5.87, 6.91, 4.97 and 4.58, respectively P<0.05). The expression of MMP-9 protein increased gradually after focal cerebral ischemia.The expression of MMP-9 protein in lentivirus intervention group was lower than MCAO group.The differences were statistically significant at each point (t values at different time points were 3.55, 6.11, 4.67, 4.63 and 2.77, respectively P<0.05).

Lentivirus mediated shRNA inhibits the expression of MMP-9, reduces the vasogenic edema and plays a protective role in cerebral infarction.Magnetic resonance DTI can monitor dynamically the changes of ischemic area in rats with ischemic cerebral infarction.

To investigate the effects of hepcidin on iron, osteoclasts and bone mass in iron accumulation mice.

Eight-week old C57/BL6 male mice were divided into control group (CTR group), high iron group (Fe group) and iron reduction group (Hepc group). CTR group and Fe group were wild-type mice, Hepc group were hepcidin gene overexpression mice.Fe group and Hepc group were injected intraperitoneally with iron, and the mice in the CTR group were injected intraperitoneally with the same amount of saline.Three groups of mice were injected with tamoxifen to induce hepcidin overexpression.Eight weeks later, specimens of three groups of mice were collected and the serum levels of hepcidin, ferritin and carboxy-terminal telopeptides (CTX) were measured by enzyme linked immunosorbent assay (ELISA). Frozen section and Prussian blue stain were carried out to detect bone iron.Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect osteoclast related gene expression[cytokinin (CTK), matrix metalloprotein (MMP9), protein tyrosine kinase 2β(PTK2β), cathepsin K (CTSK)]. Tartrate resistant acid phosphatase (TRAP) staining was used to observe the proliferation and differentiation of osteoclasts.The osteoclast activity was examined by lacunar resorption pits.The microstructure of the femur was measured by micro-computed tomography (Micro-CT). Variance analysis was applied to compare the differences among groups.

The levels of serum hepcidin in CTR, Fe and Hepc group were (508±42), (728±82) and (1 423±85) ng/L, respectively; serum ferritin were (355±26), (1 270±35) and (801±23) μg/L, respectively; CTX were (4.4±0.5), (13.9±1.4) and (8.5±0.6) mg/L, respectively; there were significant differences in the up-mentioned indexes among the three groups ( F=129.6, 781.7, 77.3, all P<0.05). The genes expression level of CTK, MMP9, PTK2β, TRAP, CTSK in the Hepc and CTR group were all significantly lower than those in Fe group (F=39.6, 8.0, 5.4, 19.5, 8.8, all P<0.05). The results of TRAP staining and pits formation also showed that osteoclast proliferation and activity in group Hepc reduced significantly when compared with those in Fe group (t=4.295, 7.557, both P<0.05).

The overexpression of hepcidin can down-regulate the content of ferritin in iron-accumulating mice and inhibit the proliferation, differentiation and activity of osteoclasts, and improve the bone mass.

To investigate if Dishevelled 2 (DVL2) regulates the apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) via the JAK-STAT pathway.

DVL2 overexpressed lentivirus was transfected into RA-FLS and the apoptosis rate was detected by flow cytometry. The effect of DVL2 on RA-FLS signaling pathway was detected by RNA-seq, and then the key genes were verified by RT-PCR.

Compared with the control group, DVL2 significantly increased the apoptosis rate of MH7A (3.2%±2.2% vs 25.7%±4.5%). RNA-seq results showed that DVL2 down-regulated the JAK-STAT pathway.The results of RT-PCR showed that DVL2 inhibited the gene expression of JAK2, Stat1, and Stat2; DVL2 still inhibited the gene expression of JAK2 and Stat2 but not Stat1 after TNF-α stimulation.DVL2 inhibited the gene expression of Bcl-xL, and the gene expression of Bcl-2 and Bcl-xL after TNF-α stimulation.

DVL2 can increase the apoptosis rate of RA-FLS through inhibiting the JAK-STAT pathway and its downstream anti-apoptotic gene.

The 25-year-old male was admitted to the hospital on December 23, 2016 due to "low back pain and numbness and weakness of both lower limbs for more than 2 months". When the patient was 6 years old, he had unstable walking, walking with the lateral plantar as the fulcrum, and his legs were sore. After 1 year of rest, the symptoms were relieved. At the age of 14, the patient developed enlarged deformity of interphalangeal joints of both upper limbs, accompanied by bilateral hip and knee pain, and unsteady walking. I was treated with hormone according to "rheumatoid arthritis", and the symptoms were temporarily relieved and then aggravated again (sudden discontinuation of the drug). I was treated with symptomatic treatment such as hemodialysis, traditional Chinese medicine and anti-osteoporosis, and the symptoms were relieved. At the age of 22, the patient had weakness, numbness, pain in both lower limbs, difficulty in walking, and disturbance in defecation and defecation without obvious triggers, T₁₁Sub-plane hypoesthesia. MRI showed multi-level disc herniation in the thoracic spine, and posterior thoracic decompression and internal fixation were performed in the local hospital. More than 2 months ago, the patient again experienced numbness, pain and weakness in both lower limbs, hypersensitivity below the umbilical plane, weakness in stool, and control of urine. For further diagnosis and treatment, he came to our hospital. The patient's parents were of normal height, and there was no history of close relatives in his family. Admission physical examination: height 171 cm, weight 66 kg, mild scoliosis of the spine, positive bilateral hip tenderness, swelling of both knees, wrists, metacarpophalangeal and proximal interphalangeal joints, no tenderness, limited movement of bilateral elbow and knee joints, and positive bilateral "4" sign. Hyperesthesia in the subumbilical plane, muscle strength of both lower limbs grade 3+, muscle strength of both upper limbs grade 5, bilateral knee tendon and Achilles tendon hyperreflexia, lumbar function score of 8 by the Japanese Orthopedic Society (JOA). There were no obvious abnormalities in rheumatological immunological and hematological examinations, and the preoperative imaging data were shown inFigure 1。 Admission diagnosis: multi-level disc herniation combined with spinal stenosis (thoracic vertebra, lumbar vertebra); Late-onset spinal epiphyseal dysplasia with progressive osteoarthropathy (SEDT-PA).

With the accelerating aging process of Chinese society, the number of elderly patients with neurodegenerative diseases (including Alzheimer's disease, Parkinson's disease, etc.) is increasing day by day, which has caused a serious burden and impact on China's public health system. Traditionally, senile neurodegenerative diseases are usually divided into two categories: one is the disease spectrum dominated by cognitive impairment (various types of dementia represented by Alzheimer's disease), and the other is the disease spectrum dominated by movement disorders (various types of movement disorders represented by Parkinson's disease and Parkinson's syndrome). However, in fact, many movement disorders can cause cognitive impairment, such as Parkinson's dementia, progressive supranuclear palsy dementia, etc. On the contrary, it is not uncommon for cognitive disorders to have movement disorders, such as extrapyramidal symptoms of Lewy body dementia and apraxia in patients with Alzheimer's disease.

In recent years, tumor immunotherapy has brought new hopes to patients with malignant tumors, especially the treatment of immune checkpoint inhibitors has made great progress, but there is still a lack of markers to predict efficacy. The analysis of tumor mutation burden and mismatch repair defects based on sequencing technology are the most studied immunotherapy markers at present. With the development of new generation sequencing technology, whole exon sequencing provides an opportunity for the above analysis. The role of whole exon sequencing in predicting tumor immunotherapy is reviewed as follows, and its application progress in glioma immunotherapy is analyzed.