Effect of chemogenetic manipulation of PVN corticotropin-releasing factor-expressing neurons on excitability of presympathetic neurons in SHR / 中国药理学通报

Aim To observe the effect of corticotropin-releasing factor ( CRF) -expressing neurons on presympathetic neurons in hypothalamic paraventricular nucleus ( PVN) of normotensive Wistar Kyoto ( WKY) rats or spontaneously hypertensive rats (SHR) , and to elucidate the underlying neuronal circuit mechanism of central sympathetic hyperexcitability. Methods The expression levels of CRF protein in WKY rats and SHR PVN were determined by Western blot. Meanwhile, the WKY and SHR PVN CRF-expressing neurons and presympathetic neurons were observed by immunofluo-rescent staining. Adult WKY rats and SHR were used in this study. By microinjection of Cre-dependent ade-no-associated viruses ( AAV) that specifically recognized the CRF promoter and AAV of chemogenetics into the PVN, CRF-expressing neurons expressed designer receptors exclusively activated by designer drugs (DREADDs). Human M3 muscarinic DREADD coupled to Gq receptor ( hM3 Dq) was specifically expressed in PVN CRF-expressing neurons in WKY rats, while human M4 muscarinic DREADD coupled to Gi receptor ( hM4Di) was specifically expressed in PVN CRF-expressing neurons in SHR. Clozapine-N-oxide (CNO) , as a designer ligand, would couple to excitatory hM3Dq or inhibitory hM4Di to regulate the excitability of PVN CRF-expressing neurons. Then the PVN presympathetic neurons were retrogradely labeled by microinjection of fluosecent tracer into the intermedio-lateral column (IML) of spinal cord. Lastly, whole cell patch clamp was used to determine the effect of CNO (10 jjumol L~ ) on spontaneous excitatory postsynaptic currents ( sEPSCs) and current-evoked firing of PVN presympathtic neurons of WKY rats and SHR. Results The expression of CRF protein in the PVN of SHR was significantly higher than that of WKY rats, and the activity and number of CRF-expressing neurons in the PVN of SHR were increased. PVN CRF-expressing neurons were expressed with chemogenetic DREADDs and PVN presympathetic neurons were retrogradely labeled with fluorescent tracer in WKY rats and SHR. In SHR expressed with chemogenetic inhibitory hM4Di-mCherry of PVN CRF-expressing neurons, bath application of CNO to the brain slices resulted in a significant decrease in sEPSCs frequency, but no change in their amplitude of labeled PVN presympathetic neurons. In contrast, in WKY rats expressed with excitatory hM3Dq-eGFP of PVN CRF-expressing neurons, CNO had no obvious effect on the sEPSCs frequency and amplitude in PVN presympathetic neurons. Furthermore, bath application of CNO had no significant effect on current-evoked firing of PVN presympathetic neurons of either WKY rats with hM3Dq-eGFP expression in CRF neurons or SHR with hM4Di-mCherry expression in CRF neurons. Conclusions The activity and number of PVN CRF-expressing neurons are increased in SHR, and CRF-expressing neurons enhance the excitability of presympathetic neurons, which acts as a regulatory neuronal microcircuit between CRF neurons and presympathetic neurons in the PVN.

KCNQ Channels in the Mesolimbic Reward Circuit Regulate Nociception in Chronic Pain in Mice / 神经科学通报·英文版

Mesocorticolimbic dopaminergic (DA) neurons have been implicated in regulating nociception in chronic pain, yet the mechanisms are barely understood. Here, we found that chronic constructive injury (CCI) in mice increased the firing activity and decreased the KCNQ channel-mediated M-currents in ventral tegmental area (VTA) DA neurons projecting to the nucleus accumbens (NAc). Chemogenetic inhibition of the VTA-to-NAc DA neurons alleviated CCI-induced thermal nociception. Opposite changes in the firing activity and M-currents were recorded in VTA DA neurons projecting to the medial prefrontal cortex (mPFC) but did not affect nociception. In addition, intra-VTA injection of retigabine, a KCNQ opener, while reversing the changes of the VTA-to-NAc DA neurons, alleviated CCI-induced nociception, and this was abolished by injecting exogenous BDNF into the NAc. Taken together, these findings highlight a vital role of KCNQ channel-mediated modulation of mesolimbic DA activity in regulating thermal nociception in the chronic pain state.

Clinical features of coronavirus disease 2019 in children: a systemic review of severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019 / 中国当代儿科杂志

OBJECTIVE@#To systematically summarize the clinical features of coronavirus disease 2019 (COVID-19) in children.@*METHODS@#PubMed, Embase, Web of Science, The Cochrane Library, CNKI, Weipu Database, and Wanfang Database were searched for clinical studies on COVID-19 in children published up to May 21, 2020. Two reviewers independently screened the articles, extracted data, and assessed the risk of bias of the studies included. A descriptive analysis was then performed for the studies. Related indices between children with COVID-19 and severe acute respiratory syndromes (SARS) or Middle East respiratory syndrome (MERS) were compared.@*RESULTS@#A total of 75 studies were included, with a total of 806 children with COVID-19. The research results showed that the age of the children ranged from 36 hours after birth to 18 years, with a male-female ratio of 1.21 : 1. Similar to SARS and MERS, COVID-19 often occurred with familial aggregation, and such cases accounted for 74.6% (601/806). The children with COVID-19, SARS, and MERS had similar clinical symptoms, mainly fever and cough. Some children had gastrointestinal symptoms. The children with asymptomatic infection accounted for 17.9% (144/806) of COVID-19 cases, 2.5% (2/81) of SARS cases, and 57.1% (12/21) of MERS cases. The children with COVID-19 and MERS mainly had bilateral lesions on chest imaging examination, with a positive rate of lesions of 63.4% (421/664) and 26.3% (5/19) respectively, which were lower than the corresponding positive rates of viral nucleic acid detection, which were 99.8% and 100% respectively. The chest radiological examination of the children with SARS mainly showed unilateral lesion, with a positive rate of imaging of 88.9% (72/81), which was higher than the corresponding positive rate of viral nucleic acid detection (29.2%). Viral nucleic acid was detected in the feces of children with COVID-19 or SARS, with positive rates of 60.2% (56/93) and 71.4% (5/7) respectively. The children with COVID-19 had a rate of severe disease of 4.6% (31/686) and a mortality rate of 0.1% (1/806), the children with SARS had a rate of severe disease of 1.5% (1/68) and a mortality rate of 0%, and those with MERS had a rate of severe disease of 14.3% (3/21) and a mortality rate of 9.5% (2/21).@*CONCLUSIONS@#Children with COVID-19 have similar symptoms to those with SARS or MERS, mainly fever and cough. Asymptomatic infection is observed in all three diseases. Children with COVID-19 or SARS have milder disease conditions than those with MERS. COVID-19 in children often occurs with familial aggregation. Epidemiological contact history, imaging examination findings, and viral nucleic acid testing results are important bases for the diagnosis of COVID-19.

Awareness, treatment and control of hypertension in 640 000 adults in eastern China / 中华流行病学杂志

To understand the awareness, treatment, and control of hypertension in residents aged 35-75 years in eastern China, analyze the treatment mode for antihypertensive agents while identifying those factors affecting awareness, treatment and control. The data collected in eastern China from the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project were used to obtain the information about the awareness, treatment and control of hypertension in the residents and the antihypertensive medication treatment mode in this area. Multilevel mixed-effects model was used to explore the association of the demographic characteristics of hypertension patients with the rates of awareness, treatment and control of hypertension. A total of 640 539 participants aged 35-75 years, mean age (56.9±9.6) years, were included in the analysis, women accounted for 59.7 and 318 741 (49.8) of the participants suffered from hypertension. Among those hypertensive patients, 46.5 were aware of their condition, 38.1 were taking prescribed antihypertensive medications, and 11.1 had achieved the control of hypertension, the differences were significant among provinces, between urban area and rural area and among different demographical groups. Calcium-channel blockers was the most commonly used medication (45.1), and 78 735 hypertension patients (86.2) took only one type of medication. Older age, higher household income, higher level of education, and histories of myocardial infarction, stroke and diabetes were associated with higher awareness, treatment and control of hypertension (<0.05). The rates of awareness, treatment and control of hypertension were low in residents in eastern China. The differences in hypertension management were significant among provinces and between urban area and rural area. Further efforts are needed to enhance the system of hypertension prevention, screening, diagnosis and treatment.

Effect of medial meniscus extrusion on arthroscopic surgery outcome in the osteoarthritic knee associated with medial meniscus tear: a minimum 4-year follow-up / 中华医学杂志(英文版)

BACKGROUND@#The potential benefit of arthroscopic surgery for osteoarthritic knee associated with medial meniscus tear is controversial. This study was conducted to determine the effect of pre-operative medial meniscus extrusion (MME) on arthroscopic surgery outcomes in the osteoarthritic knee associated with medial meniscus tear during a minimum 4-year follow-up.@*METHODS@#This was a retrospective review of a total of 131 patients diagnosed with osteoarthritic knee associated with medial symptomatic degenerative meniscus tear who underwent arthroscopic surgery from January 2012 to December 2014 and were observed for more than 4 years. Patients were classified into two groups: MME ≥3 mm (major MME group, n = 54) and MME <3 mm (non-major MME group, n = 77). Clinical assessments, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and radiographic assessments, including the Kellgren-Lawrence (K-L) grade and medial joint space width (JSW), were evaluated pre-operatively and at final follow-up. The longitudinal changes of clinical and radiographic parameters (WOMAC and the medial JSW change, K-L grade progression) were compared between groups unadjusted and adjusted for age, sex, and body mass index. Four-year survival rates (without progression to knee replacement [KR]) were also evaluated using a log-rank test and Cox proportional hazard regression model.@*RESULTS@#Major MME was present in 41% of patients. After a minimum 4-year follow-up, the mean WOMAC total and pain scores improved significantly in both groups. However, the medial JSW and K-L grade worsened significantly. Patients with pre-operative major MME worsened more in WOMAC total (adjusted mean difference [MD] 3.800, 95% confidence interval [CI]: 0.900, 11.400; P = 0.037) and function (adjusted MD 3.100, 95% CI: 0.700, 6.300; P = 0.038) scores than patients with pre-operative non-major MME, and no significant difference was observed in WOMAC pain and stiffness score between groups. The group with major MME had significantly higher joint space narrowing (adjusted MD -0.630, 95% CI: -1.250, -0.100; P = 0.021) and K-L rate progression (adjusted mean relative risk [RR] 1.310, 95% CI: 1.100, 1.600; P = 0.038) than the group with non-major MME. There was a significantly more KR progression in patients with major MME compared with those with non-major MME (adjusted RR 3.100, 95% CI: 1.100, 9.200; P = 0.042 and adjusted hazard ratio 3.500, 95% CI 1.100, 9.500; P = 0.022).@*CONCLUSIONS@#Osteoarthritic knee patients associated with medial meniscus tear with non-major MME are more responsive to arthroscopic surgery in terms of the clinical and radiologic outcomes and survival for at least 4-year follow-up; however, in terms of pain relief, arthroscopic surgery in patients with major MME is also beneficial as well as in patients with non-major MME.

Effect of medial meniscus extrusion on arthroscopic surgery outcome in the osteoarthritic knee associated with medial meniscus tear: a minimum 4-year follow-up / 中华医学杂志(英文版)

Background@#The potential benefit of arthroscopic surgery for osteoarthritic knee associated with medial meniscus tear is controversial. This study was conducted to determine the effect of pre-operative medial meniscus extrusion (MME) on arthroscopic surgery outcomes in the osteoarthritic knee associated with medial meniscus tear during a minimum 4-year follow-up.@*Methods@#This was a retrospective review of a total of 131 patients diagnosed with osteoarthritic knee associated with medial symptomatic degenerative meniscus tear who underwent arthroscopic surgery from January 2012 to December 2014 and were observed for more than 4 years. Patients were classified into two groups: MME ≥3 mm (major MME group, n = 54) and MME <3 mm (non-major MME group, n = 77). Clinical assessments, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and radiographic assessments, including the Kellgren-Lawrence (K-L) grade and medial joint space width (JSW), were evaluated pre-operatively and at final follow-up. The longitudinal changes of clinical and radiographic parameters (WOMAC and the medial JSW change, K-L grade progression) were compared between groups unadjusted and adjusted for age, sex, and body mass index. Four-year survival rates (without progression to knee replacement [KR]) were also evaluated using a log-rank test and Cox proportional hazard regression model.@*Results@#Major MME was present in 41% of patients. After a minimum 4-year follow-up, the mean WOMAC total and pain scores improved significantly in both groups. However, the medial JSW and K-L grade worsened significantly. Patients with pre-operative major MME worsened more in WOMAC total (adjusted mean difference [MD] 3.800, 95% confidence interval [CI]: 0.900, 11.400; P = 0.037) and function (adjusted MD 3.100, 95% CI: 0.700, 6.300; P = 0.038) scores than patients with pre-operative non-major MME, and no significant difference was observed in WOMAC pain and stiffness score between groups. The group with major MME had significantly higher joint space narrowing (adjusted MD -0.630, 95% CI: -1.250, -0.100; P = 0.021) and K-L rate progression (adjusted mean relative risk [RR] 1.310, 95% CI: 1.100, 1.600; P = 0.038) than the group with non-major MME. There was a significantly more KR progression in patients with major MME compared with those with non-major MME (adjusted RR 3.100, 95% CI: 1.100, 9.200; P = 0.042 and adjusted hazard ratio 3.500, 95% CI 1.100, 9.500; P = 0.022).@*Conclusions@#Osteoarthritic knee patients associated with medial meniscus tear with non-major MME are more responsive to arthroscopic surgery in terms of the clinical and radiologic outcomes and survival for at least 4-year follow-up; however, in terms of pain relief, arthroscopic surgery in patients with major MME is also beneficial as well as in patients with non-major MME.

Association of single nucleotide polymorphisms of ABCB1, OPRM1 and COMT with pain perception in cancer patients / 华中科技大学学报（医学）（英德文版）

Pain perception is influenced by multiple factors. The single nucleotide polymorphisms (SNPs) of some genes were found associated with pain perception. This study aimed to examine the association of the genotypes of ABCB1 C3435T, OPRM1 A118G and COMT V108/158M (valine 108/158 methionine) with pain perception in cancer patients. We genotyped 146 cancer pain patients and 139 cancer patients without pain for ABCB1 C3435T (rs1045642), OPRM1 A118G (rs1799971) and COMT V108/158M (rs4680) by the fluorescent dye-terminator cycle sequencing method, and compared the genotype distribution between groups with different pain intensities by chi-square test and pain scores between groups with different genotypes by non-parametric test. The results showed that in these cancer patients, the frequency of variant T allele of ABCB1 C3435T was 40.5%; that of G allele of OPRM1 A118G was 38.5% and that of A allele of COMT V108/158M was 23.3%. No significant difference in the genotype distribution of ABCB1 C3435T (rs1045642) and OPRM1 A118G (rs1799971) was observed between cancer pain group and control group (P=0.364 and 0.578); however, significant difference occurred in the genotype distribution of COMT V108/158M (rs4680) between the two groups (P=0.001). And the difference could not be explained by any other confounding factors. Moreover, we found that the genotypes of COMT V108/158M and ABCB1 C3435T were associated with the intensities of pain in cancer patients. In conclusion, our results indicate that the SNPs of COMT V108/158M and ABCB1 C3435T significantly influence the pain perception in Chinese cancer patients.

Expression of enhancer of zeste homolog 2 in esophageal squamous cell carcinoma and its prognostic value in postoperative patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of enhancer of zeste homolog 2 (EZH2) in esophageal squamous cell carcinoma and its association with the prognosis of postoperative patients.</p><p><b>METHODS</b>Surgical specimens were obtained from 102 patients with esophageal squamous cell carcinoma undergoing radical resection in our hospital from 1996 to 2006. Immunochemistry was employed to examine EZH2 protein expressions in the specimens, including 102 carcinoma tissue specimens, 30 adjacent tissue specimens and 30 normal esophageal tissue specimens. The expression levels of EZH2 were analyzed in relation to the clinicopathological parameters of the patients including gender, age, tumor differentiation, TNM, and lymph node metastasis. The postoperative patients were followed up to analyze the association of EZH2 expression with the clinical outcomes.</p><p><b>RESULTS</b>The esophageal squamous cell carcinoma tissue showed a higher EZH2 expression than the adjacent and normal esophageal tissues. EZH2 expression was higher in poorly differentiated carcinoma than in well differentiated tissue, and also higher in cases with lymph node metastasis than those without; the expression was higher in TNM stage II/III patients than in stage I patients but lower than in stage IV patients. The patients with low EZH2 expression was found to have a longer survival time than those with high EZH2 expression (P<0.05).</p><p><b>CONCLUSION</b>EZH2 plays an important role in the differentiation and metastasis of esophageal squamous cell carcinoma, and a high EZH2 expression is associated with a poor outcome in the the postoperative patients.</p>

Major risk-stratification models fail to predict outcomes in patients with multivessel coronary artery disease undergoing simultaneous hybrid procedure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The hybrid procedure for coronary heart disease combines minimally invasive coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) and is an alternative to revascularization treatment. We sought to assess the predictive value of four risk-stratification models for risk assessment of major adverse cardiac and cerebrovascular events (MACCE) in patients with multivessel disease undergoing hybrid coronary revascularization.</p><p><b>METHODS</b>The data of 120 patients were retrospectively collected and the SYNTAX score, EuroSCORE, SinoSCORE and the Global Risk Classification (GRC) calculated for each patient. The outcomes of interest were 2.7-year incidences of MACCE, including death, myocardial infarction, stroke, and any-vessel revascularization.</p><p><b>RESULTS</b>During a mean of 2.7-year follow-up, actuarial survival was 99.17%, and no myocardial infarctions occurred. The discriminatory power (area under curve (AUC)) of the SYNTAX score, EuroSCORE, SinoSCORE and GRC for 2.7-year MACCE was 0.60 (95% confidence interval 0.42 - 0.77), 0.65 (0.47 - 0.82), 0.57 (0.39 - 0.75) and 0.65 (0.46 - 0.83), respectively. The calibration characteristics of the SYNTAX score, EuroSCORE, SinoSCORE and GRC were 3.92 (P = 0.86), 5.39 (P = 0.37), 13.81 (P = 0.32) and 0.02 (P = 0.89), respectively.</p><p><b>CONCLUSIONS</b>In patients with multivessel disease undergoing a hybrid procedure, the SYNTAX score, EuroSCORE, SinoSCORE and GRC were inaccurate in predicting MACCE. Modifying risk-stratification models to improve the predictive value for a hybrid procedure is needed.</p>

Experiences of transcallosal-interforniceal approach for resection of the third ventricle and the pineal region tumors: report of 24 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the advantages and disadvantages of transcallosal-interforniceal approach for resection of the third ventricle and the pineal region tumors.</p><p><b>METHODS</b>The clinical data of 24 cases from July 2008 to March 2011 were retrospectively analyzed. All 24 patients operated by transcallosal-interforniceal approach, among them, there were 14 males and 10 females, with a average age of 32 years ranged from 17 to 65 years and with medical history from 1 month to 10 years. Issues of managements were analyzed and discussed, including reasonable incision design, the managements of draining vein, the site and the length of the incision of the corpus callosum, tumor exposure in increased intracranial pressure, prevention of complications, skills of surgery, treatments of obstructive hydrocephalus, and postoperative managements.</p><p><b>RESULTS</b>In the 24 cases, there were 5 cases of pineal parenchymal tumors, 4 cases of germinoma, 3 cases of astrocytoma, 2 cases of hypothalamus hamartomas, 2 cases of ependymoma, 2 cases of mixed germ cell tumour, 2 cases of malignant lymphomas, 1 case of pineoblastoma, 1 case of dermoid cyst, 1 case of chordoid glioma and 1 case of craniopharyngioma. After surgeries, total removal achieved in 9 cases, and subtotal removal in 10 cases and partial removal in 5 cases. Operative mortality was 0. Combined third ventriculostomy were performed in 13 cases. Postoperative complications occurred in 5 cases, including frontoparietal epidural hematoma in 1 case; postoperative short-term memory loss in 3 cases, postoperative memory loss within 1 month in 2 cases and within 3 months in 1 case; frontoparietal subdural effusion in 1 case and the effusion disappeared without any treatment. Ventriculoperitoneal shunt was performed in 1 case.</p><p><b>CONCLUSIONS</b>The transcallosal-interforniceal approach is ideal for the removal of tumors in third ventricle as well as majority tumor in posterior of third ventricle in a skillful hand. Tumor resection combined with third ventriculostomy is the significant advantages in the approach.</p>

Analysis on complications of elastic nail treating children's long bone fractures / 中国骨伤

<p><b>OBJECTIVE</b>To analyze the reasons on complications of treatment with elastic nail in children's long bone fracture.</p><p><b>METHODS</b>Sixty-six cases (75 parts of long bone fratures) were treated by elastic nail including 49 male and 17 female. The age ranged from 3 to 17 years, mean 7.8 years. There were 35 femur fractures (2 cases were hibateral), 20 tibia and fibula fractures (12 cases were tibia fractures), 8 radial fractures (1 case was ulna fracture) and 3 humerus fractures. The cases included 4 open fractures and 62 closed fractures. All cases were fresh fractures, no multi-segmental fractures. Three cases associated with brain and chest injuries. These cases were treated by open or closed reduction and internal fixaion with elastic nail. A cast or brace had been used after operation for a month. Following-up included the function of the joint,the bottom of the nail and the callus. Complications were timely recorded.</p><p><b>RESULTS</b>All the patients were followed-up for 12 to 29 months, averaged 17 months. The cases occurrenced compilications including 2 cases of nonunion, 2 of new fracture, 1 of displacment, 4 of joint dysfunction, 3 of irritation of the bottom of the nail and 1 malunion.</p><p><b>CONCLUSION</b>Strict indication, well design,canonical operation is a good way to avoid compliacations. At the same time,early treatment can reduce the sequela.</p>

WNKs: protein kinases with a unique kinase domain

WNKs (with-no-lysine [K]) are a family of serine-threonine protein kinases with an atypical placement of the catalytic lysine relative to all other protein kinases. The roles of WNK kinases in regulating ion transport were first revealed by the findings that mutations of two members cause a genetic hypertension and hyperkalemia syndrome. More recent studies suggest that WNKs are pleiotropic protein kinases with important roles in many cell processes in addition to ion transport. Here, we review roles of WNK kinases in the regulation of ion balance, cell signaling, survival, and proliferation, and embryonic organ development.

Mechanism of dracorhodin perchlorate-induced Hela cell apoptosis / 药学学报

<p><b>AIM</b>To study the mechanism of dracorhodin perchlorate-induced Hela cell apoptosis.</p><p><b>METHODS</b>Cell viability was measured by MTT method. Morphological changes were observed by phase contrast microscopy and Hoechst 33258 staining. DNA fragmentation was assayed by agarose gel electrophoresis. Protein expression was detected by Western blot analysis.</p><p><b>RESULTS</b>Dracorhodin perchlorate induced Hela cell apoptosis. The apoptosis was partially reversed by caspase-1, -3, -8, -9 and caspase family inhibitors. Treatment of Hela cells with dracorhodin perchlorate for 12 h increased the protein expression ratio of Bax/Bcl-XL; procaspase-3, -8, ICAD and PARP were cleaved to smaller molecules.</p><p><b>CONCLUSION</b>Dracorhodin perchlorate induced Hela cell death via alteration of Bax/Bcl-XL ratio and activation of caspases.</p>