The application of positron emission tomography in the research and development of central nervous system drugs / 中国临床药理学与治疗学

Positron emission tomography (PET) now plays an important role in the research and development (R&D) of central nervous system (CNS) drugs. PET could characterize the biodistribution, pharmacokinetics, and receptor binding of CNS drugs quantitatively. The present review summarized the quantitative methods of PET used in the pharmacokinetics and receptor occupancy analysis of CNS drugs. Moreover, the present review listed various applications of PET supporting R&D of CNS drugs, which could provide a new direction for the R&D of CNS drugs.

LONP1 ameliorates liver injury and improves gluconeogenesis dysfunction in acute-on-chronic liver failure / 中华医学杂志(英文版)

BACKGROUND@#Acute-on-chronic liver failure (ACLF) is a severe liver disease with complex pathogenesis. Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis. Accumulating evidence suggests that glucose metabolic disturbance, especially gluconeogenesis dysfunction, plays a critical role in the disease progression of ACLF. Lon protease-1 (LONP1) is a novel mediator of energy and glucose metabolism. However, whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.@*METHODS@#In this study, we collected liver tissues from ACLF patients, established an ACLF mouse model with carbon tetrachloride (CCl 4 ), lipopolysaccharide (LPS), and D-galactose (D-gal), and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model. LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation. Liver histopathology, biochemical index, mitochondrial morphology, cell viability and apoptosis, and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF.@*RESULTS@#We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues. Furthermore, LONP1 overexpression remarkably attenuated liver injury, which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in ACLF mice. Moreover, mitochondrial morphology was improved upon overexpression of LONP1. Meanwhile, the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression. Similarly, the hepatoprotective effect was also observed in the hepatocyte injury model, as evidenced by improved cell viability, reduced cell apoptosis, and improved gluconeogenesis level and activity, while LONP1 knockdown worsened liver injury and gluconeogenesis disorders.@*CONCLUSION@#We demonstrated that gluconeogenesis dysfunction exists in ACLF, and LONP1 could ameliorate liver injury and improve gluconeogenic dysfunction, which would provide a promising therapeutic target for patients with ACLF.

Treatment of Irritable Bowel Syndrome by Chinese Medicine: A Review / 中国结合医学杂志

Irritable bowel syndrome (IBS) is a common refractory disease. Chinese medicine (CM) has remarkable efficacy and advantages on the treatment of IBS. This review summarized the articles focusing on the treatment of IBS with CM to sum up the latest treatment methods for IBS and the underlying mechanisms. Literature analysis showed that prescriptions, acupuncture, and moxibustion are the primary methods of CM treatment for IBS. The potential mechanism centers on the regulation of the enteric nervous system, the alleviation of visceral hypersensitivity, the stability of intestinal flora, and the regulation of the immune system.

18F-MK6240 PET imaging of tau protein in Alzheimer′s disease and cognitive correlation analysis / 中华核医学与分子影像杂志

Objective:To investigate the tau deposition pattern in Alzheimer′s disease (AD) and its correlation with cognition by 18F-MK6240 PET imaging. Methods:From August 2021 to February 2022, 46 elderly people over 55 years old (16 males, 30 females; age (68.9±7.7) years) were included from outpatient and community in Shanghai. Structural brain MRI, β-amyloid (Aβ) PET imaging, tau-PET imaging and comprehensive neuropsychological tests batteries were conducted. The subjects were divided into AD group ( n=16) and normal cognition (NC) group ( n=30) according to the 2018 National Institute on aging and Alzheimer′s Association (NIA-AA) diagnostic criteria. Quantitative analysis was conducted to investigate the tau deposition pattern in AD after preprocessing 18F-MK6240 PET images with MRI images. SUV ratio (SUVR) of brain regions such as entorhinal cortex, hippocampus, parahippocampal gyrus, amygdala, insular lobe, frontal lobe, precuneus, occipital lobe, thalamus and putamen were analyzed, with cerebellum as reference region. The differences of tau deposition in brain regions between AD and NC groups were analyzed by independent-sample t test. The associations between SUVR and Mini-Mental State Examination (MMSE) score and Montreal Cognitive Assessment-Basic (MoCA-B) score were analyzed by Pearson correlation analysis. Results:AD displayed a significant tau deposition in frontal lobes, temporal lobes and parietal lobes compared with NC. SUVR of brain regions in AD group were higher than those in NC group ( t values: 3.37-9.61, all P<0.05). SUVR in brain regions were negatively correlated with MMSE score ( r values: from -0.735 to -0.350, all P<0.05) and MoCA-B score ( r values: from -0.723 to -0.367, all P<0.05). Conclusion:18F-MK6240 PET can demonstrate the tau deposition in the brain of AD patients, and the tau deposition is related to cognitive function.

Effects of fibroblast growth factor receptor 3 and human papillomavirus type 2 E2 protein on the differentiation of keratinocytes: a preliminary study / 中华皮肤科杂志

Objective:To evaluate regulatory effects of fibroblast growth factor receptor 3 (FGFR3) and human papillomavirus type 2 (HPV2) E2 protein on the differentiation of an immortalized human keratinocyte line HaCaT and a normal human epidermal keratinocyte line NHEK.Methods:In both HaCaT and NHEK cells, HPV2 E2-stably transfected cell lines (HPV2 E2-transfected groups) were established by using the lentivirus transfection method, wide-type FGFR3-overexpressing cells (FGFR3-WT transfected groups) and FGFR3-K650E mutant-overexpressing cells (FGFR3-K650E transfected groups) were constructed by using the plasmid transfection method, and cells transfected with blank vectors served as control groups (blank vector control groups). Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of HPV2 E2, and Western blot analysis to determine the protein expression of HPV2 E2, FGFR3, and keratinocyte differentiation markers including loricrin, filaggrin, as well as involucrin. Laser scanning confocal microscopy was conducted to observe the spatial localization of HPV2 E2 and FGFR3 in HaCaT cells. Statistical analysis was carried out by using two-independent-sample t test for the comparison between two groups, one-way analysis of variance for the comparison among multiple groups, and Dunnett t-test for multiple comparisons. Results:The HPV2 E2-stably transfected cell lines were successfully constructed, and the expression of HPV2 E2 FLAG protein was significantly higher in the HPV2 E2-transfected groups than in the blank vector control groups in both HaCaT and NHEK cells ( t = 13.71, 25.91, respectively, both P < 0.001) ; both FGFR3-WT and FGFR3-K650E were successfully overexpressed in both HaCaT and NHEK cells, and the FGFR3 protein expression was significantly higher in the FGFR3-WT transfected groups and the FGFR3-K650E transfected groups than in the blank vector control groups ( F = 473.90, 579.90, respectively, both P < 0.001). In both HaCaT and NHEK cells, the expression of keratinocyte differentiation markers including loricrin, filaggrin, and involucrin was significantly upregulated in the HPV2 E2-transfected groups, the FGFR3-WT transfected groups, and the FGFR3-K650E transfected groups than in the blank vector control groups (all P < 0.05). In the HPV2 E2-stably transfected HaCaT and NHEK cells, the expression of loricrin, filaggrin, and involucrin was significantly down-regulated in the HPV2 E2 + FGFR3-WT transfected groups and the HPV2 E2 + FGFR3-K650E transfected groups than in the HPV2 E2 + blank vector groups (all P < 0.05). Laser scanning confocal microscopy showed the spatial co-localization of HPV2 E2 and FGFR3 in the nuclear membrane and cytoplasm of HaCaT cells. Conclusion:HPV2 E2 and FGFR3 could both induce the differentiation of HaCaT and NHEK cells, while FGFR3 could inhibit HPV2 E2-induced differentiation trend of HaCaT and NHEK cells, which may be related to the cellular spatial co-localization of HPV2 E2 and FGFR3.

Imaging study of β-amyloid deposits in preclinical Alzheimer′s disease patients in communities of Shanghai / 中华核医学与分子影像杂志

Objective:To explore the β-amyloid (Aβ) deposition pattern of subjects with the preclinical Alzheimer′s disease (AD), community-derived amnestic mild cognitive impairment (aMCI) and normal cognition (NC) from communities of Shanghai.Methods:According to the inclusion and exclusion criteria, 273 subjects (104 males, 169 females; age (64.2±7.6) years) were recruited from Shanghai community and memory clinics from December 2018 to July 2020. All subjects underwent MRI, 18F-AV45 PET imaging and neuropsychological scale tests and were grouped into AD, aMCI and NC groups based on clinical diagnosis. Differences in demographic information, the neuropsychological scale tests′ scores and positive rate of Aβ deposition among each group were analyzed by one-way analysis of variance or χ2 test. Aβ deposition patterns of AD and MCI groups were analyzed at voxel level, and the differences of Aβ deposition among different groups were compared. Results:Among 273 patients, the positive rates of Aβ deposition in AD, aMCI and NC groups were 84.4%(38/45), 36.4%(20/55) and 23.1%(40/173), respectively ( χ2=58.37, P<0.001). Among AD, aMCI, NC and NC (Aβ-) groups ( n=132), the education years of AD group was the lowest ((9.7±4.6) years; F=8.86, P<0.001). In addition, there were significant differences in the scores of several neuropsychological scale tests among AD, aMCI, NC groups and NC (Aβ-) group ( F values: 27.68-235.50, all P<0.001). Compared with subjects in NC(Aβ-) group, the Aβ depositions in the aMCI and AD groups were widely distributed in the whole cerebral cortex; and AD group had higher Aβ deposition in bilateral frontal, parietal, temporal, occipital lobe, cingulate gyrus and precuneus than aMCI group. Conclusions:The positive rate of Aβ deposition in the preclinical AD population from the Shanghai community is obtained. There are significant different Aβ deposition patterns in subjects at different stages of AD.

Distinguish mild cognitive impairment and normal cognitive change by β-amyloid PET imaging / 中华核医学与分子影像杂志

Objective:To explore the association of the impaired cognition and the deposition of β-amyloid (Aβ) in normal cognitive (NC) and mild cognitive impairment (MCI).Methods:From December 2018 to January 2021, 305 subjects (113 males, 192 females; age (64.0±7.7) years) who completed neuropsychological tests and MRI in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University and 18F-florbetapir (AV45) PET imaging in Huashan Hospital, Fudan University were retrospectively analyzed. The subjects were divided into MCI group and NC group based on neuropsychological tests, and each group was further divided into Aβ-positive and Aβ-negative based on PET imaging results. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Results:There were 118 subjects in MCI group and 187 subjects in NC group. The Aβ-positive rate in MCI group (37.3%, 44/118) was higher than that in NC group (26.2%, 49/187; χ2=4.19, P=0.041). The assessment performances of MCI group in general cognitive function, memory function, language function and executive function were inferior to those of NC group ( t values: from -10.63 to -6.31, z values: from -11.01 to -6.03, all P<0.001). The Auditory Verbal Learning Test-Long Delay Recall (AVLT-LDR) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in MCI group (1.00(0.00, 3.00) and 3.00(1.00, 4.00); z=-2.49, P=0.013). The Montreal Cognitive Assessment Basic (MoCA-B) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in NC group (25.29±2.67 and 26.36±2.42; t=-2.61, P=0.010). Conclusion:Compared to Aβ-negative subjects, MCI patients with Aβ-positive perform worse on memory tests, and NC subjects with Aβ-positive perform worse on general cognitive function.

Effect of different immunization schedules on diphtheria antibody level among preschool children in Shenzhen / 中国学校卫生

Objective@#To evaluate the immunity and influencing factors of diphtheria among preschool children in Shenzhen,to provide reference for effective monitoring of diphtheria IgG antibody level in preschool children.@*Methods@#Serum samples were collected from 296 preschool children aged 4-6 who were recruited in Shenzhen. The diphtheria antibody titer in serum was determined by enzyme linked immunosorbent assay, and the effect of different immumuzation schedule including types of vaccine and vaccination timing, on the geometric mean concentration (GMC) of diphtheria IgG antibody and antibody positive rate were analyzed.@*Results@#The GMC of diphtheria IgG antibody was 0.71 IU/mL, and the positive conversion rate was 33.1%. There were significant differences in antibody GMC and antibody positive conversion rate of diphtheria in different age groups( F/χ 2=11.77, 27.45, P < 0.01 ). The GMC and antibody positive conversion rate showed significant differences by diphtheria antibodies, vaccine types and end dose vaccination intervals( F=49.53, 12.95，11.61, P <0.01). There were statistically significant differences in the positive conversion rate of diphtheria antibodies in children with different types of diphtheria antibodies, vaccine types of diphtheria antibodies, and diphtheria antibodies at the time interval of final vaccination (Fisher exact probability method, P <0.01).@*Conclusion@#The overall positive conversion rate of diphtheria antibody in preschool children in Shenzhen is high. Timely completion of full diphtheria vaccination can improve the antibody level and plays a better role in protecting preschool children.

An improved fixation method for preparing mouse brown adipose tissue for transmission electron microscopy / 解剖学报

Objective To improve the fixation method of the transmission electron microscope for better morphological preservation of mitochondria and lipid droplets in mouse brown adipose tissue. Methods The fixation method for mouse brown adipose tissue was optimized, mainly including an increased concentration of paraformaldehyde from 2% to 4% in the pre-fixative, employment of transcardial perfusion followed by immersion fixation in pre-fixation, and using imidazole-buffered osmium tetroxide as the post-fixative. The ultrastructures of brown adipocytes prepared by the improved method were observed and compared with those of a known standard protocol (3 mice in each group). The improved method was further validated in the quantitative analysis of mitochondrial cristae density and lipid droplets. Results The mitochondrial cristae and membrane structure of other organelles of brown adipocytes were better preserved using the optimized method compared with those of the standard method. Lipid droplets were presented as round structures with high electron density instead of vacuolated appearances. Using this method, we observed that the density of mitochondrial cristae and the content of lipid droplets increased in brown adipocytes after cold adaptation. Conclusion The optimized method can better preserve the ultrastructure of organelles in brown adipocytes, especially mitochondria and lipid droplets, and ma)' be applicable for studying the ultrastructures remodeling of brown adipose tissue under different physiological or pathological conditions.

Nerve repair effect of olanzapine-mediated cyclic AMP response element binding protein/brain-derived neurotrophic factor/receptor tyrosine kinase receptors B pathway on schizophrenic rats / 解剖学报

Objective To stud)' the nerve repair effect of olanzapine on schizophrenia model rats through its effect on cyclic AMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/receptor tyrosine kinase receptors B (TrkB) pathway. Methods Total 60 rats were divided into control group, model group, olanzapine low, middle and high dose group. The rats in the model group, olanzapine low, middle and high dose groups were injected intraperitoneally with MK-801[0. 2 mg/(kg-d) ], while the control injected with the same amount of normal saline. The low, middle and high dose olanzapine groups were perfused with olanzapine solution of 0. 5 mg/(kg-d),1. 0 mg/(kg-d) and 1. 5 mg/(kg-d) respectively. The behavior of rats was scored according to ataxia and stereotyped behavior standards, cognitive function and learning ability were evaluated by Moms water maze test, serum tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) levels were detected by ELISA method, hippocampal histopathology was observed under microscope, and apoptosis and expression of CREB/BDNF/TrkB pathway related proteins in hippocampus were detected. Results Compared with the control group, the ataxia, the score of stereotyped behavior, the expression of TNF-a, IL-6 and the rate of apoptosis in the model group increased significantly (P < 0 . 01). Compared with the control group, the number of crossing the platform, the time of staying in the target quadrant and the relative expression of CREB, p-CREB, p-TrkB, TrkB and BDNF protein in the model group decreased significantly (P<0. 01), and those in the low and middle dose olanzapine groups decreased significantly (P < 0 . 05). Compared with the model group, the times of crossing the platform and the stay time in the target quadrant increased significantly in the low and middle dose olanzapine groups (P< 0. 05). In the model group and the low dose olanzapine group, the hippocampal cells were swollen obviously, the nucleus was broken and divided, pyknosis, and the tissue aiTangement was disorderly, while the phenomenon of fragmentation and nuclear pyknosis was rarely seen in the middle and high dose olanzapine groups. Conclusion The nerve repair mechanism of olanzapine on schizophrenic model rats is related to improving cognitive impainnent, protecting hippocampal neurons and activating the expression of CREB/BDNF/TrkB signal pathway in rats.

Therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea in rats and its metabolomic analysis / 中国中药杂志

This study aimed to investigate the therapeutic effect of Leonuri Herba aqueous decoction on primary dysmenorrhea(PD) and explore the underlying mechanism in conjunction with untargeted metabolomics. Forty adult female rats were randomly divi-ded into a normal group, a model control group, ibuprofen(0.12 g·kg~(-1)) group, and high-and low-dose Leonuri Herba aqueous decoction(5 and 2.5 g·kg~(-1)) groups, with eight rats in each group. The PD rat model was prepared using intramuscular injection of estradiol benzoate combined with intraperitoneal injection of pitocin. Drugs were administered by gavage from the 4th day of modeling for 7 d. After the last administration, pitocin was injected intraperitoneally, and the writhing latency and writhing times within 30 min were recorded. The uterine and ovarian coefficients were determined. Estradiol(E_2), progesterone(Prog), oxytocin(OT), cyclooxyge-nase 2(COX-2), prostaglandin E_2(PGE_2), prostaglandin F_(2α)(PGF_(2α)), and Ca~(2+) levels in uterine tissues were measured by ELISA and biochemical kits. Morphological changes in uterine and ovarian tissues were observed by hematoxylin-eosin(HE) staining. The protein expression of oxytocin receptor(OTR), prostaglandin E_2 receptor 3(EP3), and estrogen receptor alpha(ERα) in uterine tissues was detected by immunohistochemistry. The mRNA expression of OTR, PGE_2 receptors 1-4(EP1, EP2, EP3, and EP4), and PGF_(2α) receptor(FP) in uterine tissues was detected by quantitative real-time PCR. Untargeted metabolomics analysis was performed by ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-QTOF-MS) technology to screen potential biomarkers and enrich metabolic pathways. The results showed that Leonuri Herba was able to significantly reduce the writhing times in PD rats(P<0.05 or P<0.01), significantly reduce the uterine and ovarian coefficients(P<0.01), and improve their histomorphology. After treatment with Leonuri Herba, PGE_2 content was significantly increased(P<0.05), COX-2, PGF_(2α) and Ca~(2+) content, and PGF_(2α)/PGE_2 was significantly decreased(P<0.05 or P<0.01), and OT content was decreased, while E_2 and Prog content tended to further increase in uterine tissues of PD rats. Correspondingly, OTR and EP3 protein expression was significantly downregulated(P<0.05 or P<0.01) and ERα protein expression was upregulated(P<0.05) in uterine tissues. The mRNA expression of FP and EP4 in uterine tissues was significantly downregulated(P<0.01), and the mRNA expression of EP1, EP3, and OTR showed a decreasing trend. The untargeted metabolomics results showed that 10 differential metabolites were restored in the plasma of PD rats after Leonuri Herba treatment. The results indicate that Leonuri Herba is effective in the prevention and treatment of PD, and the underlying mechanism may be attributed to the regulation of PGs synthesis and corresponding receptor binding.

Current status and problems of human resources of centers for disease control and prevention in Kashgar District， Xinjiang Uygur Autonomous Region / 上海预防医学

ObjectiveTo evaluate the current situation of human resource allocation in district and county centers for disease control and prevention （CDCs） in Kashgar ， identify existing problems and influencing factors， and to provide scientific evidence for optimizing the human resource allocation. MethodsA survey was conducted among all CDCs in Kashgar in February 2022. The questionnaire included the institutional and individual questions. ResultsThe overall staff size approved for the CDCs in Kashgar was 604， with a staffing rate of 76.17%， among which the staffing rates in 5 county CDCs were less than 60%. Currently， there were a total of 524 approved staff members in all CDCs， resulting in a vacancy rate of 13.25%. In the district CDC， 85 staff members were on duty， while the median of staff on duty was 34 in each county CDC. The staff in the district CDC was ageing， of which those aged over 45 accounted for 67.06%. The staff in the county CDCs was generally young， of which those aged less than 35 accounted for 54.22%. Moreover， the proportion of staff with bachelor’s degree or above in the district and county CDCs was 31.76% and 24.95%， respectively. The proportion of staff without professional title was 32.94% and 48.03%， respectively. In contrast， the proportion of those with middle and senior professional title was 57.89% and 22.02%， respectively. In addition， in recent 3 years， 24 staff members resigned in the CDCs， all of whom had professional titles. ConclusionHuman resources are insufficient in CDCs in Kashgar. Furthermore， staff structure is unreasonable， with a serious loss of human resources. In particular， the district CDC needs to optimize the allocation of human resources.

Study of altered brain metabolism and connectivity in temporal lobe epilepsy / 中华核医学与分子影像杂志

Objective:To explore the abnormal brain metabolic pattern and connectivity in temporal lobe epilepsy (TLE) patients.Methods:18F-FDG PET images of 75 patients diagnosed as drug resistant unilateral TLE from January 2014 to December 2016 in Huashan Hospital of Fudan University were collected retrospectively, including 41 (22 males, 19 females, age (28.4±8.7) years) left TLE (LTLE) and 34 (13 males, 21 females, age (28.5±8.8) years) right TLE (RTLE). Forty-four healthy controls (24 males, 20 females, age (31.2±6.2) years) were also enrolled. The cerebral glucose metabolism in TLE patients and the controls were analyzed with statistical parametric mapping (SPM) 12. The brain connectivity based on glucose metabolism were analyzed with bilateral hippocampus and amygdala as seeds. Permutation test with 1 000 permutations was used to analyze data. Results:Compared to control group, in both LTLE and RTLE groups, hypometabolism was found in affected hippocampus, amygdala, insula and temporal gyrus and hypermetabolism was observed in health hippocampus, parahippocampal gyrus, amygdala, lenticular nucleus and thalamus. In addition, hypometabolism was also found in affected superior/middle frontal gyrus and hypermetabolism was also found in bilateral frontal-orbital gyrus, bilateral cerebellum, affected lenticular nucleus and thalamus in LTLE group. In both TLE groups, affected seeds exhibited increased connectivity with affected superior frontal gyrus, lingual gyrus, fusiform gyrus, superior/middle temporal gyrus and temporal pole (all P<0.05); affected seeds exhibited increased connectivity with health superior frontal gyrus ( P=0.005), lingual gyrus ( P=0.018) and transverse temporal gyrus ( P=0.016) in RTLE group in addition. Besides, affected seeds exhibited decreased connectivity with bilateral default mode network (DMN) (all P<0.05), affected caudate nucleus ( P=0.015) and health thalamus ( P=0.008), in a uniform distribution pattern in LTLE group, and with bilateral cerebral cortex in an irregular distribution pattern in RTLE group (all P<0.05). In LTLE group, health seeds exhibited more increased connections with superior ( P=0.005)/middle frontal gyrus ( P=0.042), health hippocampus ( P=0.038), parahippocampal gyrus ( P=0.019), amygdala ( P=0.038), posterior cingulate gyrus ( P=0.004), and bilateral fusiform gyrusand ( P=0.048) compared with RTLE group; while, in RTLE group, health seeds exhibited more decreased connections with health superior ( P=0.047), inferior frontal gyrus ( P<0.001), orbital frontal gyrus ( P<0.001) and rectus gyrus ( P=0.016) compared with LTLE group. Conclusion:Altered brain glucose metabolism and connectivity pattern are found and will elucidate the underlying metabolic pattern of TLE.

Expert consensus on gastrointestinal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine / 中华危重病急救医学

Acute gastrointestinal dysfunction is a common and important complication of sepsis. As no exiting formal definition and classification of gastrointestinal dysfunction, most of the treatment strategies for gastrointestinal dysfunction are not based on clinical evidence, but on their own clinical experience. Experts of traditional Chinese medicine, integrated traditional Chinese and Western medicine and Western medicine from various disciplines in Shanghai are organized by the Shanghai Society of Integrated Traditional Chinese and Western Medicine and the Emergency Department Branch of Shanghai Physicians Association. After repeated discussion, literature search and formulation of the outline, we developed consensus on gastrointestinal dysfunction secondary to sepsis with integrating Traditional Chinese Medicine and Western medicine by consulting extensively on clinical experts in the fields of emergency medicine, gastroenterology, general surgery, infectious medicine and traditional Chinese medicine, and holding several expert forums and consultation meetings. This clinical expert consensus focused on acute gastrointestinal injury (AGI) classification and inducer of sepsis. In this consensus, the common symptoms, diagnosis, classifications, treatment strategies and suggestions of acute gastrointestinal injury or dysfunction secondary to sepsis were explored from the aspect of both Traditional Chinese Medicine and Western medicine.

Ginsenoside Rg1 Reduces Cardiotoxicity While Increases Cardiotonic Effect of Aconitine in vitro / 中国结合医学杂志

OBJECTIVE@#To explore the synergic mechanism of ginsenoside Rg1 (Rg1) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs.@*METHODS@#The toxic, non-toxic, and effective doses of AC and the most suitable compatibility concentration of Rg1 for both normal and damaged NRCMs exposed for 1 h were filtered out by 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, respectively. Then, normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg1 for 1 h, and the cellular activity, cellular ultrastructure, apoptosis, leakage of acid phosphatase (ACP) and lactate dehydrogenase (LDH), intracellular sodium ions [Na+], potassium ions [K+] and calcium ions [Ca2+] levels, and Nav1.5, Kv4.2, and RyR2 genes expressions in each group were examined.@*RESULTS@#For normal NRCMs, 3000 µ mol/L AC significantly inhibited cell viability (P<0.01), promoted cell apoptosis, and damaged cell structures (P<0.05), while other doses of AC lower than 3000 µ mol/L and the combinations of AC and Rg1 had little toxicity on NRCMs. Compared with AC acting on NRCMs alone, the co-treatment of 3000 and 10 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ (P<0.01 or P<0.05), and the co-treatment of 3000 µ mol/L AC with 1 µ mol/L Rg1 significantly decreased the level of intracellular Ca2+ via regulating Nav1.5, RyR2 expression (P<0.01). For damaged NRCMs, 1500 µ mol/L AC aggravated cell damage (P<0.01), and 0.1 and 0.001 µ mol/L AC showed moderate protective effect. Compared with AC used alone, the co-treatment of Rg1 with AC reduced the cell damage, 0.1 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular Na+ (P<0.05), 1500 µ mol/L AC with 1 µ mol/L Rg1 significantly inhibited the level of intracellular K+ (P<0.01) via regulating Nav1.5, Kv4.2, RyR2 expressions in impaired NRCMs.@*CONCLUSION@#Rg1 inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na+], [K+], and [Ca2+].

The effects of the recommended prescription for COVID-2019-lung-spleen qi deficiency on in vitro SARS-CoV-2 replication and pro-inflammatory factors expression / 中国药理学通报

Aim To determine the antiviral and anti-inflammatory effects of the recommended prescription for COVID-2019-lung-spleen qi deficiency(4-1)against in vitro infection of SARS-CoV-2 and common coronaviruses.Methods The main chemical substances of 4-1 were analyzed by LC-MS.The toxicity and antiviral effects of of 4-1 were detected by MTT and by CPE assay, respectively.The viral loads in cell supernatant and the expression of inflammatory factors induced by viral infection were determined by qRT-PCR.Results The recommended prescription 4-1 contained 94 chemical compounds, including flavonoids, steroids, sesquiterpenoids, and so on.The range of selection indexes for SARS-CoV-2 and common coronaviruses was 8.44±0.4952.26±2.3.This prescription could inhibit the proliferation of SARS-CoV-2, the expression of ACE2 and S mRNA, and down regulate IL-1α and CCL-5/RANTES at 10, 5, and 2.5 g•L-1 doses.Further, at doses of 20, 10 and 5 g•L-1, it could inhibit the proliferation of three common coronaviruses and suppress the overexpression of IL-6, CXCL-8/IL-8, CXCL-10/IP-10, TNF-α, IFN-α, CCL-2/MCP-1, MIG and CCL-5/RANTES induced by OC43/229E infection.The inhibitory effects were dose-dependent.Conclusions The prescription 4-1 has antiviral and anti-inflammation effects against multiple coronaviruses.This study provides the research basis for the treatment of common respiratory viral infections and emerging infectious diseases such as COVID-19 by using traditional Chinese medicine.

Clinical outcomes of single-port insufflation endoscopic subcutaneous nipple-sparing mastectomy in early breast cancer / 国际外科学杂志

Objective:To discuss the oncologic safety, aesthetic outcome, and upper extremity function of single-port insufflation endoscopic nipple-sparing mastectomy (SIE-NSM) in the treatment of early breast cancer.Methods:From January 2014 to August 2019, a total of 80 patients with stage Ⅰ and Ⅱ breast cancer underwent SIE-NSM, at Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed and followed up. Estimated the oncologic safety, aesthetic outcome, and upper extremity function.Results:SIE-NSM was performed successfully on all 80 patients.There was no serious complication after surgery.The follow-up time was 16-82 months and the median follow-up time was 42 months. Local recurrence occurred in two patients, and there was no distant metastases. Four (5%) patients developed grade 1-3 nipple-areola complex ischemia. There were no cases of subcutaneous effusion.The satisfaction with breasts, chest well-being, psychosocial well-being, and sexual well-being scores were confirmed to be highly rated by Breast-Q scale. Upper extremity function score confirmed that good upper limb function was preserved after surgery. The mean length of incision was (3.6±0.8) cm, and the blood loss was (24.7±19.3) mL.Conclusions:SIE-NSM can achieve a higher cosmetic score and a better recovery of upper limb function on the premise of ensuring the safety of the tumor.This novel method is an appropriate surgical option for patients with early breast cancer.

Research progress in non-drug treatment of essential hypertension by Traditional Chinese Medicine / 国际中医中药杂志

Non-drug therapy of traditional Chinese medicine (TCM) mainly includes exercise therapy, such as Baduanjin and Taichi. Some TCM techniques adjunct toanti-hyperhension drugs show effectiveness with safety, such as moxibustion, acupuncture, acupoint application, auricular point application, massage, cupping, scraping, herbal tea, emotional therapy, and music therapy. In future, long-term follow-up of trials and standardization of research are needed. In the other way, in-depth research on patients with grade 3 hypertension and secondary hypertension is still needed.

Expression of miR-7850 in renal cell carcinoma and its effect on proliferation and migration of renal cell carcinoma / 中国医师杂志

Objective:To observe the expression of microRNA (miRNA, miR) -7850 in renal cancer tissues, and to explore the effect of miR-7850 on the proliferation and migration of renal cancer cells and on the regulation of serine proteinase inhibitor B3 (SERPINB3) gene expression.Methods:Real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-7850 in renal cancer tissues and renal cancer cell lines. The renal cell carcinoma cell line with the lowest expression of miR-7850 was selected, and the negative control sequence (miR-NC) and miR-7850 mimics were transfected into renal cell carcinoma cells by Lipofectamine 2000 transfection reagent, respectively, which were defined as miR-NC group and miR-7850 group. qRT-PCR was used to detect the expression of miR-7850 in transfected renal cancer cells. The cell proliferation and migration ability after transfection were detected by cell counting kit-8 (CCK-8) method and transwell experiment. Bioinformatics prediction and dual luciferase reporter gene experiments were used to verify the target gene of miR-7850. qRT-PCR and Western blot were used to detect the expression of target genes in renal cancer cells after transfection.Results:Compared with adjacent tissues (5.95±0.44), the expression of miR-7850 in kidney cancer tissues (1.19±0.33) was lower ( P<0.01). Compared with immortalized proximal renal tubular epithelial cells (1.01±0.07), the expression of miR-7850 was lower in renal cancer cell lines ( P<0.05), and the lowest in A498 cells (0.13±0.01) ( P<0.01). The expression of miR-7850 in the miR-7850 group (7.46±0.93) was significantly higher than that in the miR-NC group (1.01±0.08) ( P<0.01), indicating successful transfection. Compared with the miR-NC group, the cell proliferation ability of the miR-7850 group was significantly reduced ( P<0.05). The number of migrating cells in miR-NC group and miR-7850 group were (139.50±12.31) and (75.09±16.05) cells, respectively, and the cell migration ability in miR-7850 group decreased significantly ( P<0.01). Bioinformatics technology shows that the target gene of miR-7850 was SERPINB3. The dual luciferase reporter gene experiment confirmed that miR-7850 can target the SERPINB3 gene ( P<0.05). Compared with the miR-NC group, the expression of SERPINB3 in cells of miR-7850 group was significantly reduced ( P<0.05), as well as the CDK4, CyclinD, Snail and Vimentin. Conclusions:miR-7850 is lowly expressed in renal cancer tissues and cell lines. miR-7850 can inhibit the proliferation and migration of renal cancer A498 cells, which may be related to its inhibition of SERPINB3 gene expression.

Use of three-dimensional computer reconstruction in diagnosis and treatment of hilar cholangiocarcinoma / 中华肝胆外科杂志

Objective:To study the use of three-dimensional computer reconstruction in diagnosis and treatment of hilar cholangiocarcinoma.Methods:A retrospective analysis of clinical data was conducted on patients with hilar cholangiocarcinoma admitted to the Department of General Surgery, the First Affiliated Hospital of the University of Science and Technology of China from January 1, 2017 to July 31, 2019. The classification of hilar cholangiocarcinoma, vascular invasion and surgical resectability were determined by preoperative three-dimensional reconstruction. These data were then compared with the findings obtained during operations, by comparing with the three-dimensional reconstruction technology findings in classification of hilar cholangiocarcinoma, vascular invasion, and hilar extent of biliary and vasculature involvement.Results:Of 65 patients included in this study, there were 35 males and 30 females, with an age of (60.35±10.70) years. After operation, these 65 patients were classified into type I ( n=7), type II ( n=4), type III ( n=14), and type IV ( n=40) using the Bismuth classification. The accuracy rates of preoperative three-dimensional reconstruction for hilar cholangiocarcinoma classification, portal vein invasion, hepatic artery invasion, and diagnosis of hilar cholangiocarcinoma vasculature involvement were 90.7% (59/65), 90.7% (59/65), 86.1% (56/65) and 80.0% (52/65) respectively. Conclusions:The three-dimensional computer reconstruction technology could visually and accurately display the shape and spatial extent of hilar cholangiocarcinoma. It has an important clinical use in accurately diagnosing hilar cholangiocarcinoma preoperatively.