[Establishment of a topographic map assessment system for facial and cervical wounds and scars of burn patients based on the Delphi method].

Objective: To construct a targeted and accurate evaluation system for facial and cervical wounds and scars of burn patients. Methods: The method combining literature analysis and survey research was adopted, and the basic principles of item system construction were followed. From June to August 2020, based on the aesthetic standards of facial and cervical plastic surgery, the topographic map assessment system for facial and cervical wounds and scars of burn patients was preliminarily formed, focusing on the assessment of wounds and scars in the necks and faces of patients after burns. In September 2020, 38 experts in the relevant fields were consulted in advance and the questionnaire was revised according to the experts' opinions. From December 2020 to March 2021, the Delphi method was applied to conduct inquiry by correspondence with 35 experts in relevant fields from Guangzhou, Shenzhen, Shanghai, Beijing, and other cities, who met the inclusion criteria, and the items were screened and established. The effective recovery rate of inquiry questionnaire was calculated to determine the level of enthusiasm of experts, the average authority coefficient of all items was calculated to determine the level of expert authority, the average importance expert score, the average coefficient of variation, and the average full score rate of all the third-level items were calculated to determine the concentration of expert opinions, the average coefficients of variation and Kendall's harmony coefficients of the importance, sensitivity, and operability expert scores of all the third-level items were calculated to determine the degree of coordination of expert opinions. The Kendall's harmony coefficients for the importance, sensitivity, and operability expert scores of all the third-level items were statistically analyzed with chi-square test. Results: Among the 35 experts consulted by Delphi method, mainly were male, aged (48±10) years, with 8-38 years of working experience, mainly with associate senior titles and above, all with a bachelor's degree or above education background, and of whom 11 were burn experts, 7 were wound repair experts, 4 were plastic surgery experts, and 13 were rehabilitation medicine experts. Finally, a topographic map assessment system for facial and cervical wounds and scars of burn patients was formed, including 4 first-level items, 21 second-level items, 40 third-level items, and 1 mask. The effective recovery rate of inquiry questionnaire was 100% (35/35). The average authority coefficient of all items was 0.89. The average importance expert score was 4.67, the average coefficient of variation of importance expert score was 0.01, and the average full score rate of all the third-level items was 86.3%. The average coefficients of variation of the importance, sensitivity, and operability expert scores of all the third-level items were 0.01, 0.01, and 0.02, respectively. The Kendall's harmony coefficients for the importance, sensitivity, and operability expert scores of all the third-level items were statistically significant (with χ2 values of 1 201.53, 745.67, and 707.07, respectively, P<0.05). Conclusions: The established topographic map assessment system for facial and cervical wounds and scars of burn patients has high scientificity and reliability, which can be used for the evaluation of facial and neck wounds or scars in burn patients.

[Correction of the pathogenic mutation in the G6PC3 gene by adenine base editing in mutant embryos].

Objective: To determine whether the adenine base editor (ABE7.10) can be used to fix harmful mutations in the human G6PC3 gene. Methods: To investigate the safety of base-edited embryos, off-target analysis by deep sequencing was used to examine the feasibility and editing efficiency of various sgRNA expression vectors. The human HEK293T mutation models and human embryos were also used to test the feasibility and editing efficiency of correction. Results: ①The G6PC3(C295T) mutant cell model was successfully created. ②In the G6PC3(C295T) mutant cell model, three distinct Re-sgRNAs were created and corrected, with base correction efficiency ranging from 8.79% to 19.56% . ③ ABE7.10 could successfully fix mutant bases in the human pathogenic embryo test; however, base editing events had also happened in other locations. ④ With the exception of one noncoding site, which had a high safety rate, deep sequencing analysis revealed that the detection of 32 probable off-target sites was <0.5% . Conclusion: This study proposes a new base correction strategy based on human pathogenic embryos; however, it also produces a certain nontarget site editing, which needs to be further analyzed on the PAM site or editor window.

Living myocardial slices: Advancing arrhythmia research.

Living myocardial slices (LMS) are ultrathin (150-400 µm) sections of intact myocardium that can be used as a comprehensive model for cardiac arrhythmia research. The recent introduction of biomimetic electromechanical cultivation chambers enables long-term cultivation and easy control of living myocardial slices culture conditions. The aim of this review is to present the potential of this biomimetic interface using living myocardial slices in electrophysiological studies outlining advantages, disadvantages and future perspectives of the model. Furthermore, different electrophysiological techniques and their application on living myocardial slices will be discussed. The developments of living myocardial slices in electrophysiology research will hopefully lead to future breakthroughs in the understanding of cardiac arrhythmia mechanisms and the development of novel therapeutic options.

Gigabit per second visible light communication based on AlGaInP red micro-LED micro-transfer printed onto diamond and glass.

Full-color smart displays, which act both as a display and as a high-speed visible light communication (VLC) transmitter, can be realized by the integration of red-green-blue micron-sized light emitting diodes (micro-LEDs) onto a common platform. In this work, we report on the integration of aluminum gallium indium phosphide red micro-LEDs onto diamond and glass substrates by micro-transfer printing and their application in VLC. The device on-diamond exhibits high current density and bandwidth operation, enabled by diamond's superior thermal properties. Employing an orthogonal frequency division multiplexing modulation scheme, error-free data rates of 2.6 Gbps and 5 Gbps are demonstrated for a single micro-LED printed on-glass and on-diamond, respectively. In a parallel configuration, a 2x1 micro-LED array achieves error-free data rates of 3 Gbps and 6.6 Gbps, on-glass and on-diamond, respectively.

On-chip GaN-based dual-color micro-LED arrays and their application in visible light communication.

Integrated multi-color micron-sized light emitting diode (micro-LED) arrays have been demonstrated in recent years for display applications; however, their potential as visible light communication (VLC) transmitters is yet to be fully explored. In this work, we report on the fabrication and characterization of on-chip dual-color micro-LED arrays and their application in VLC. For this purpose, blue-green and blue-violet micro-LED arrays were fabricated by transfer printing blue-emitting micro-LEDs onto the substrate of green and violet micro-LEDs, respectively. The potential of these dual-color micro-LED arrays as VLC transmitters is demonstrated with respective error-free data rates of 1.79 and 3.35 Gbps, achieved by the blue-green and blue-violet devices in a dual wavelength multiplexing scheme.

A randomised controlled trial of stepwise sputum collection to increase yields of confirmed tuberculosis.

The proportion of bacteriologically confirmed tuberculosis (TB) in China has decreased far below the worldwide average. To investigate whether stepwise measures to ensure sputum quality can improve the rate of bacteriologically confirmed TB. We enrolled 980 adults with suspected TB from three counties in China during 2017 for this multicentre randomised controlled trial. Half the participants (n = 490) were randomly assigned to intervention groups that received instructions by a study nurse, and sputum induction, if necessary. In the remaining 490 patients, sputum samples were collected without observation. The primary outcome was the proportion of patients detected as bacteriologically positive on smear, culture or molecular assays (EasyNAT or Xpert). Bacteriological confirmation rates were significantly higher in the intervention than in the control group: overall (159/490 [32%] vs. 122/490 [25%]; P = 0.009); confirmation using smear (17% vs. 11%; P = 0.010); confirmation using culture (28% vs. 21%; P = 0.021); and confirmation using molecular assays (27% vs. 18%; P = 0.001). Most of the improvement was in patients who received instruction alone, while improvement was greatest in younger patients (adjusted odds ratio 1.27, 95%CI 1.05-1.53 per 10 years). If implemented effectively in resource-limited primary care clinics, our simple stepwise procedure combining instruction and sputum induction could increase the proportion of bacteriologically confirmed TB significantly. .

[A clinical analysis of insulin antibody in type 2 diabetic patients].

This study was conducted to evaluate the relationship between serum insulin levels and the production of insulin antibody (IA) in type 2 diabetes (T2DM). A total of 647 T2DM were included. Among them, 20.9% patients were IA positive, who were elder and had a longer duration, lower BMI, a higher positive rate of glutamic acid decarboxylase antibody(GADAb) and higher serum insulin levels during an insulin secretion test. More patients were treated with insulin in IA positive group than in IA negative group (65.9% vs 41.0%, P=0.000). Fasting serum insulin level was associated with occurrence of IA in all patients (OR=1.02, P=0.001) and insulin treated patients (OR=1.033, P=0.002). The cut-off point of fasting serum insulin level for predicting IA positive was 17.87 mIU/L (sensitivity 55.1%, specificity 89.0%). Exogenous insulin use is associated with the presence of IA. Fasting serum insulin level can be used as a predictor for the production of IA in insulin-treated patients.

Relationship between cytokine gene polymorphisms and acute rejection following liver transplantation.

Acute rejection (AR) recurrence after liver transplantation (LT) is one of the major complications that leads to chronic graft dysfunction. It has been reported that the polymorphisms in some cytokine genes are associated with human liver allograft rejection. This study mainly investigated the associations between polymorphisms in the genes encoding interleukin-10 (IL10), transforming growth factor-b1 (TGFB1), and tumor necrosis factor-a (TNF), and the risk of AR recurrence. We enrolled 359 LT recipients; they were divided into two groups: an AR group (N = 165) and a non-AR group (N = 194) according to whether they experienced rejection within the first month following liver transplantation. After providing informed consent, blood was collected and DNA was extracted. The single nucleotide polymorphisms of IL10 (-1082, -819, and -592), TGFB1 (+869 and +915), and TNF (-308) were investigated according to the methods used in previous studies. A significant difference was observed in the distribution of allelic frequencies at position +869 in TGFB1 between the AR and non-AR groups (P = 0.000). However, no significant differences (P > 0.05) were found in the genotype distributions in IL10, TNF, and TGFB1 between the AR and non-AR groups. Our study suggests that the +869 gene polymorphism of TGFB1 is significantly associated with liver graft rejection, while the other gene polymorphisms investigated in IL10, TNF, and TGFB1 are probably not risk factors for AR in LT recipients.

Tumor necrosis factor α level in cerebrospinal fluid for bacterial and aseptic meningitis: a diagnostic meta-analysis.

BACKGROUND AND PURPOSE: In our previous study, tumor necrosis factor α (TNF-α) was identified as an effective target for sepsis patients (Int J Clin Pract, 68, 2014, 520). TNF-α in cerebrospinal fluid (CSF) was also investigated for its utility in the differential diagnosis of bacterial and aseptic meningitis. However, there has been neither definite nor convincing evidence so far. Here the overall diagnostic accuracy of TNF-α in differentiation between bacterial and aseptic meningitis was evaluated through the meta-analysis of diagnostic tests. METHODS: The sensitivity, specificity and other measures of accuracy were pooled using random effect models. Summary receiver operating characteristic curves were used to assess overall test performance. Publication bias was evaluated using funnel plots, and sensitivity analysis was also introduced. RESULTS: A total of 21 studies involving bacterial meningitis (678) and aseptic meningitis (694) involved a total of 1372 patients. The pooled sensitivity and specificity for the TNF-α test were 0.83 [95% confidence interval (CI) 0.80-0.86, I(2)  = 65.1] and 0.92 (95% CI 0.89-0.94, I(2)  = 61.8), respectively. The positive likelihood ratio was 12.05 (95% CI 7.41-19.60, I(2)  = 36.5), the negative likelihood ratio was 0.17 (95% CI 0.13-0.24, I(2)  = 59.4), and TNF-α was significantly associated with bacterial meningitis, with a diagnostic odds ratio of 49.84 (95% CI 28.53-87.06, I(2)  = 47.9). The overall accuracy of the TNF-α test was very high with the area under the curve 0.9317. Publication bias was absent, and sensitivity analysis suggested that our results were highly stable. CONCLUSIONS: Our meta-analysis suggested that TNF-α could be recommended as a useful marker for diagnosis of bacterial meningitis and differential diagnosis between bacterial and aseptic meningitis with high sensitivity and specificity. Thus, hospitals should be encouraged to conduct TNF-α tests in CSF after lumbar puncture.

Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells.

Myostatin, a member of the transforming growth factor-ß superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induced significant mitochondrial metabolic alterations and prolonged exposure of myostatin induced mitochondria-dependent apoptosis in cancer cells addicted to glycolysis. To address the underlying mechanism, we found that the protein levels of Hexokinase II (HKII) and voltage-dependent anion channel 1 (VDAC1), two key regulators of glucose metabolisms as well as metabolic stress-induced apoptosis, were negatively correlated. In particular, VDAC1 was dramatically upregulated in cells that are sensitive to myostatin treatment whereas HKII was downregulated and dissociated from mitochondria. Myostatin promoted the translocation of Bax from cytosol to mitochondria, and knockdown of VDAC1 inhibited myostatin-induced Bax translocation and apoptosis. These apoptotic changes can be partially rescued by repletion of ATP, or by ectopic expression of HKII, suggesting that perturbation of mitochondrial metabolism is causally linked with subsequent apoptosis. Our findings reveal novel function of myostatin in regulating mitochondrial metabolism and apoptosis in cancer cells.

Delayed gastric emptying is related to cardiovascular autonomic neuropathy in Chinese patients with type 2 diabetes.

BACKGROUND AND STUDY AIMS: Delayed gastric emptying (DGE) is the commonest gastrointestinal (GI) complication in type 2 diabetes. We aimed to evaluate the association between DGE and cardiovascular autonomic neuropathy (CAN) in type 2 diabetes. PATIENTS AND METHODS: A total of 71 Chinese patients (39 men and 32 women, aged 60-90 years) and 30 controls (12 men and 18 women, aged 50-79 years) were studied in Nanjing, China. The gastric emptying was assessed by 13C-octanoic acid breath test (OBT) and gastric emptying ultrasonography (GEU). Cardiovascular autonomic neuropathy (CAN) was assessed by a scoring system being validated before. RESULTS: The diabetic patients, except for a higher plasma glucose level, had similar characteristics compared to the non-diabetic controls. Diabetic patients had higher incidence of DGE and CAN than controls (48.5% vs. 10.7%, p = 0.001). Among diabetic patients with DGE (n = 27), 18 (66.7%) had CAN and 9 (33.3%) did not. Corresponding figures for those without DGE (n = 39) were 14 (35.9%) and 25 (64.1%), respectively (p = 0.014). Diabetes was independently associated with the risk of DGE with odd ratio (95% CI) of 15.6 (1.92, 127.06) (p = 0.010). The presence of diabetes or CAN was independently associated with the half gastric emptying time after adjusting for age, gender, plasma glucose and blood pressure. CONCLUSIONS: We found a much prolonged gastric emptying time in Chinese patients with type 2 diabetes as compared to non-diabetic controls. There was a high rate of CAN in diabetic patients, and it was associated with gastric emptying.

[Determination of airway reactivity in the conscious and unrestrained guinea pigs].

A simple, stable determining system in the conscious and unrestrained guinea pigs was established that can quantitatively analyse the airway reactivity (AR). In this model, the response to histamine (His) or acetylcholine (ACh) aerosol was concentration-dependent with EC50 effective concentration causing 50% animals wheezing) of 53.3 mumol/m3 and 269 mumol/m3 respectively.

Effect of ONO-1078, a leukotriene antagonist, on capsaicin- and substance P-induced bronchoconstriction and airway microvascular leakage in guinea pigs.

AIM: To study the effect of 4-oxo-8-[p-(4-phenylbutyloxy) benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate (ONO-1078), a specific leukotriene antagonist, on capsaicin (Cap)-sensitive sensory nerve functions in the airways, and clarify the modulating roles of endogenous peptido-leukotrienes. METHODS: Changes in intrapulmonary pressure (IPP), Evans blue extravasation in airways, and contraction of bronchial smooth muscles of guinea pigs induced by Cap, substance P (SP) and leukotriene C4 (LTC4) were observed. RESULTS: Cap (0.05 mg.kg-1, i.v.), SP (1 microgram.kg-1, i.v.) and LTC4 (0.5 microgram.kg-1, i.v.) enhanced IPP, and Evans blue extravasation in bronchi and intrapulmonary airways. ONO-1078 0.03 mg.kg-1, i.v. completely blocked the responses to LTC4, attenuated those to Cap, but had no effect to SP. In isolated bronchial smooth muscles, ONO-1078 (1 mumol.L-1) inhibited the contractile response to Cap, but not to SP. CONCLUSION: ONO-1078 partly inhibits Cap-sensitive sensory nerve actions in airways, but has no direct effect on SP, a sensory neuropeptide.

Effects of ONO-1078, a leukotriene antagonist, on cardiovascular responses induced by vagal stimulation, capsaicin, and substance P in guinea pigs.

AIM: To determine the role of ONO-1078, 4-oxo-8 -[p-(4-phenylbutyloxy) benzoylamino]- 2-(tetrazol-5-yl) -4H-1-benzopyran hemihydrate, in cardiovascular responses induced by vagal stimulation, capsaicin, and substance P. METHODS: Evans blue extravasation in the atrium and ventricle, and mean arterial pressure (MAP) were observed. RESULTS: Electric stimulation of vagus (ESV, 10 Hz, 5 ms, 2 or 10 V, for 90 s) increased Evans blue extravasation in the hearts of atropine (1 mg.kg-1, i.v.)-pretreated guinea pigs. Capsaicin (0.05 mg.kg-1, i.v.) and substance P (1 microgram.kg-1, i.v.) enhanced the dye extravasation and elicited a drop in MAP. ONO-1078 (0.03 and 0.1 mg.kg-1, i.v.) inhibited ESV-induced response, especially at stimulation of 2 V. ONO-1078 (0.03 mg.kg-1) attenuated capsaicin-induced cardiac microvascular leakage and hypotensive response, but failed to inhibit substance P-induced responses. CONCLUSION: ONO-1078 can modulate the cardiovascular responses in neurogenic inflammation, possibly mediated by inhibiting sensory neuropeptide release.

[Progress in the study of cyclic nucleotide phosphodiesterases].

There are five families of cyclic nucleotide phosphodiesterase isozymes, which have a common structure, but have different biochemical characteristics, physiologic functions and regulatory mechanisms. Various selective phosphodiesterase inhibitors may have potential uses for antiasthmatic, inotropic, vasodilative, antithrombotic and antidepressant drugs.

Inhibitory effect of tetrandrine on C fiber activation-induced contractions in trachea and bronchus of guinea pig.

AIM: To study the inhibitory effects of tetrandrine (Tet) on an activation of the sensory nervous C fibers in isolated trachea and bronchus of guinea pig. METHOD: The electric field stimulation induced a phase II contraction of the preparations, which was due to an activation of the C fifers. The effects of Tet on phase II contraction were analyzed. RESULTS: Tet 0.3-30 mumol.L(-1) inhibited phase II contractions in a concentration-dependent manner. That phase II contractions inhibited by Tet 1 mumol.L(-1) were 40 +/- 38% and 75 +/- 22% of control in tracheae and bronchi respectively. After pretreatment with chlorphenamine or atropine phase II contraction were still reduced by Tet 1 mumol.L(-1), inhibitory rates being 70 +/- 16% and 64 +/- 16% of control, respectively. The contractile responses of the preparations to exogenous substance P, however, were unaffected by treatment with Tet 1 mumol.L(-1). CONCLUSION: Tet 1 mumol.L(-1) inhibits phase II contraction, related to the inhibition of local release of neuropeptides from C fibers of guinea pig airway.

[Inhibition of chemically induced microvascular leakage by ONO-1078, a leukotriene antagonist, in rat skin].

This study is to determine whether ONO-1078, a potent leukotriene antagonist, influences chemically induced rat skin microvascular leakage which is considered to be, at least in part, due to stimulation of sensory nerve ending and release of sensory neuropeptides. Evans blue dye was used as a tracer for plasma leakage. Intradermal injections of chemical stimuli, histamine (10 micrograms), capsaicin (10 micrograms) and formalin (0.5 mg), evoked Evans blue dye extravasation in rat skin. Intraperitoneal ONO-1078 dose-dependently inhibited the dye extravasation induced by these stimuli, with ID5v values of 1.98 mg.kg-1 for histamine, 1.78 mg.kg-1 for capsaicin, and 2.23 mg.kg-1 for formalin. In contrast to chlorpheniramine, a H1 receptor antagonist, the inhibitory effect of ONO-1078 was weaker on histamine, but more potent on capsaicin and formalin. The inhibitory effect of dexamethasone was more potent than that of ONO-1078 on these stimuli. On the other hand, ONO-1078 inhibited the dye extravasation induced by leukotriene D4 (0.05 micrograms), but showed no effect on those induced by substance P (0.5 micrograms, a sensory neuropeptide), a larger dose of histamine (100 micrograms), and bradykinin (1 microgram). These results suggest that inhibition of chemically induced skin microvascular leakage by ONO-1078 may be mediated by inhibiting the release of sensory neuropeptides from capsaicin-sensitive sensory fibers.

Mediator difference in contractions between trachea and bronchus of guinea pig induced by stimulation of C-fibers in vitro.

In trachea and bronchus of guinea pig in vitro, electric field stimulation (EFS) induced a rapid contraction (phase I) followed by a long-lasting contraction (phase II). The pretreatments of chlorphenamine (Chl) 1 mumol.L-1 and disodium cromoglycate (Cro) 10 mumol.L-1 reduced the tracheal contraction of phase II from 49 +/- 23 mg and 34 +/- 18 mg to 27 +/- 21 and 18 +/- 12 mg, respectively. The contractile responses of the tracheae to increasing concentrations of substance P (SP) 0.1-3.0 mumol.L-1 were reduced by the pretreatment of Cro 10 mumol.L-1 (P < 0.01). On the contrary, the contractile responses of the bronchi were not inhibited by Cro or Chl but were inhibited by pretreatment of atropine 1 mumol.L-1 from 61 +/- 36 mg to 36 +/- 15 mg. These results show that there are different mechanisms in the EFS-induced contractions between the trachea and bronchus; that different mediators amplify the phase II contractions.

[Releases of bradykinin and substance P by heating hind paw of rat].

Contribution of kallikrein-kinin system to heat-induced substance P (SP) release into the periphery was studied by using plasma kininogens-deficient strain Brown Norway Katholiek (B/N-Ka) and normal strain Brown Norway Kitasato (B/N-Ki) rats. Bradykinin (BK) and SP levels in the sc perfusates of the hind instep were measured by radioimmunoassay. In B/N-Ki rat, immersion of hind paw into hot water (47 degrees C) for 20 min led to an increase of BK (43 +/- s 34 fmol.min-1) and SP (11.1 +/- 9.7 fmol.min-1) in the perfusate, whereas those in B/N-Ka rat (BK 1.3 +/- 1.0 fmol.min-1 (P < 0.01), SP 5.5 +/- 3.5 fmol.min-1 (P < 0.05)) were remarkably less. Heat-induced extravasation (leakage of Evans blue) in B/N-Ka rat was also less than that in B/N-Ki rat (P < 0.05). Results suggest that kallikrein-kinin system is involved in the release of SP into the periphery, ie, BK released into the extravascular space by noxious heat stimulation intervenes in SP release.