In order to provide a reference basis for the development of relevant compound preparations， this article takes a comprehensive analysis of the usage and dosage of famous classical formulas in Han dynasty from various perspectives， and gives corresponding countermeasures on this basis. Through the comprehensive analysis of the classification and statistics of Zhongjing's medication characteristics， decoction methods， administration and dosage， and combining conversion methods of weights and measures by ancient medical practitioners， along with the dosage and administration of the listed Han dynasty famous classical formulas， it was found that the "Jiangxi method" served as a general guideline for administration according to Zhongjing's original text. This method allowed for flexible dosing based on the conversion of the ancient measurements to modern equivalents［13.8 g per Liang（两）］， ensuring the safe and effective medication of these formulas. After combing， it is found that although the dosage of single medicine is large in famous classical formulas from Han dynasty， the administration is flexible. The crude drug amount per administration serves as the foundational dose， with the frequency of administration adjusted flexibly according to the condition. This dosing approach becomes the key for the rational development of compound formulations of famous classical formulas. Based on the conclusions of the study， it is recommended that when developing compound formulations of famous classical formulas in Han dynasty， the original administration method and dosage should be respected. The original crude drug amount per administration should be considered as the daily foundational dose， with the frequency of administration described within a range（1 to N times per day， where N is the maximum number of administrations as per the original text）. The specific frequency of administration can be adjusted flexibly by clinical practitioners based on the individual condition. This approach should also be adopted in toxicological studies， where the dosage per administration serves as the basis for toxicity research， and the toxicity profile at the maximum administration frequency should be observed， providing guidance on the clinical safety range. Corresponding drug labels should provide information within a range to indicate toxicological risk intervals.

Objective:To investigate the association between abnormal left atrial appendage function and thrombotic events in patients with non-valvular atrial fibrillation, and the independent risk factors affecting left atrial appendage function.Methods:Patients with non-valvular atrial fibrillation, who visited the Atrial Fibrillation Center of the First Affiliated Hospital of Xinjiang Medical University from June 1, 2019 to June 1, 2021, were selected. According to left atrial appendage flow velocity (LAAFV), they were divided into normal left atrial appendage function group (297 patients with LAAFV ≥ 40 cm/s) and abnormal left atrial appendage function group (85 patients with LAAFV<40 cm/s). Baseline data and transesophageal echocardiography images were collected from all the patients. The occurrence of thrombotic events was recorded. Univariate and multivariate unconditional logistic regression analyses were conducted to investigate the correlation between abnormal left atrial appendage function and the occurrence of thrombotic events.Results:There were significant differences in gender, type of atrial fibrillation, CHA 2DS 2-VASc score, anticoagulant therapy, total cholesterol, low-density lipoprotein cholesterol, international normalized ratio (INR), left atrial diameter, proportion of patients with right atrial enlargement, left ventricular ejection fraction, inner diameter, sum of inner diameter, depth, and sum of depth of all angles of the left atrial appendage, and incidence of thrombotic events between the two groups (all P<0.05). After adjusting for confounders, multivariate unconditional logistic regression analyses showed that abnormal left atrial appendage function was closely associated with thrombotic events (β=1.168 P=0.002), and left atrial diameter ( OR=1.084, 95% CI 1.019-1.153, P=0.011) and persistent atrial fibrillation ( OR=2.323, 95% CI 1.226-4.403, P=0.010) were independent risk factors affecting left atrial appendage function. Conclusions:Abnormal left atrial appendage function is closely associated with thrombosis. The left atrial diameter and persistent atrial fibrillation were independent risk factors affecting left atrial appendage function.

OBJECTIVES: Prediabetes is associated with an increased risk of cognitive impairment and neurodegenerative diseases. However, the exact mechanism of prediabetes-related brain diseases has not been fully elucidated. The brain structure of patients with prediabetes has been damaged to varying degrees, and these changes may affect the topological characteristics of large-scale brain networks. The structural covariance of connected gray matter has been demonstrated valuable in inferring large-scale structural brain networks. The alterations of gray matter structural covariance networks in prediabetes remain unclear. This study aims to examine the topological features and robustness of gray matter structural covariance networks in prediabetes. METHODS: A total of 48 subjects were enrolled in this study, including 23 patients with prediabetes (the PD group) and 25 age-and sex-matched healthy controls (the Ctr group). All subjects' high-resolution 3D T₁ images of the brain were collected by a 3.0 Tesla MR machine. Mini-mental state examination was used to evaluate the cognitive status of each subject. We calculated the gray matter volume of 116 brain regions with automated anatomical labeling (AAL) template, and constructed gray matter structural covariance networks by thresholding interregional structural correlation matrices as well as graph theoretical analysis. The area under the curve (AUC) in conjunction with permutation testing was employed for testing the differences in network measures, which included small world parameter (Sigma), normalized clustering coefficient (Gamma), normalized path length (Lambda), global efficiency, characteristic path length, local efficiency, mean clustering coefficient, and network robustness parameters. RESULTS: The network in both groups followed small-world characteristics, showing that Sigma was greater than 1, the Lambda was much higher than 1, and Gamma was close to 1. Compared with the Ctr group, the network of the PD group showed increased Sigma, Lambda, and Gamma across a range of network sparsity. The Gamma of the PD group was significantly higher than that in the Ctr group in the network sparsity range of 0.12-0.16, but there was no difference between the 2 groups (all P>0.05). The grey matter network showed an increased characteristic path length and a decreased global efficiency in the PD group, but AUC analysis showed that there was no significant difference between groups (all P>0.05). For the network separation measures, the local efficiency and mean clustering coefficient of the gray matter network in the PD group were significantly increased and AUC analysis also confirmed it (P=0.001 and P=0.004, respectively). In addition, network robustness analysis showed that the grey matter network of the PD group was more vulnerable to random damage (P=0.001). CONCLUSIONS The prediabetic gray matter network shows an increased average clustering coefficient and local efficiency, and is more vulnerable to random damage than the healthy control, suggesting that the topological characteristics of the prediabetes grey matter covariant network have changed (network separation enhanced and network robustness reduced), which may provide new insights into the brain damage relevant to the disease.
Humans ; Gray Matter/diagnostic imaging* ; Prediabetic State ; Magnetic Resonance Imaging ; Cerebral Cortex ; Brain

Objective:To analyze the gene variants in patients with primary distal renal tubular acidosis (dRTA), and explore the correlation between the genotype and phenotype.Methods:The Sanger direct sequencing or whole-exome sequencing was used to identify causal variants and the variation pathogenicity was evaluated according to 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines in 44 dRTA patients (37 families) diagnosed in the Affiliated Qingdao Municipal Hospital of Qingdao University and the Affiliated Hospital of Qingdao University from April 2010 to September 2020. The clinical features of the patients were summarized, and the correlation between the genotype and phenotype was investigated.Results:Seven variants of SLC4A1 gene, 17 variants of ATP6V0A4 gene, and 15 variants of ATP6V1B1 gene were identified in 44 patients with dRTA, and of which 11 variants were new ones. According to ACMG guidelines, the pathogenic, likely pathogenic, benign variants among the 39 variants were 22, 16 and 1, respectively. Nine patients were autosomal dominant hereditary dRTA caused by SLC4A1 gene mutation, 4 patients with autosomal recessive hereditary dRTA complicated with Southeast Asian ovalocytosis and anemia were caused by SLC4A1 gene mutation, and 14 patients caused by ATP6V0A4 gene mutation and 8 patients caused by ATP6V1B1 gene mutation were autosomal recessive hereditary dRTA; Two children with dRTA were found to carry one monoallelic defect in ATP6V1B1, and no causal gene mutation was identified in 7 patients. One patient showed incomplete dRTA, and the other 43 patients showed complete dRTA. The prevalence of sensory neural hearing loss caused by ATP6V0A4 and ATP6V1B1 mutation were 2/14 and 6/10 respectively. The frequency of chronic kidney disease in adults, children and infants were 4/4, 2/4, and 1/36, separately. After the drug treatment based on potassium citrate and sodium citrate, the growth and development (28/40) and electrolyte disturbance (41/44) of most patients were significantly improved. Conclusions:The present study has identified 39 variants of SLC4A1, ATP6V0A4 and ATP6V1B1 genes in 44 patients with dRTA, including 11 novel ones. There is a close relationship between genotype and phenotype in dRTA patients and most patients' conditions were improved after proper treatment. This study enriches the human gene mutation database and provides valuable references for diagnosis, treatment and genetic counseling in patients with dRTA.

Objective:To design an intelligent system of leak detection for AK200Shemodialysis machine so as to fast troubleshoot the range of leaked point for helpingengineer. Methods: The likely leaked part of flow paths of hemodialysis were simplified basedon routine detection experiment and the statistical record and data of faults. And then, testmode of pressure when hemodailysis implemented self-inspection for leakage was imitated. There was a air pumpwas connected with aimed flow paths, and the positive and negative pressure generated by controlling an externalair pump and the connected magnetic valve were applied at different time and different section, respectively. Afterincreased pressure, depended on the comparison of intra pressures from pressure sensors for one part of pipelinebetween pre- and post of one spell to analyze and decide whether this section exist leak. And the judgment standardwas if the difference of pressure was less than 5mmHg, there was not leak in this flow path, otherwise, the likely leakpoint should be troubleshot in further detection. Results: 183 detections were implemented at AK200S/AK200USwhich once happened alarm of leakage. And in the 183 detections, the detection system for leakage has found theranges of leaked point in 171 detection. The distribution of leaked points was: 73 times were from filter to DRVAsection, 19 times were from DRVA section to DIVA section, 79 times were from DIVA section to champ of flexiblepipe at terminal of EVVA. On the other hand, in the leaked points, 162 points were at seal ring, 1 point was at filmof valve, 8 points were at connector, and the success rate of detection for leaked fault was more than 90%. Besides,the success rate of detection for leakage on flow paths of prepare troubleshooting under normal temperature was100%. Conclusion: The detection system of self-dependant development for leakage can help engineer to save timeof troubleshooting for leaked point and enhance the work efficiency.

Objective To investigate the effect of gradient heat stress on phagocytosis of hepatic Kupffer cells (KCs) in vitro in rats. Methods Rat Kupffer cells were isolated in vitro and the temperature for gradient heat stress was set at 37, 39, 41 and 43℃. After thermal stimulation, cell injury was detected by PI and Hochest33342 staining. CCK-8 assay was used to investigate difference in cellular proliferation rate over 24h between the groups. Flow cytometry was used to investigate the influence of heat stress on the phagocytosis of KCs. Results Compared to the normal control group, cells in each heat stress group exhibited varying degrees of damage, especially cells in 43℃ group. The ratio of damage cells increased with the increase of heat stress severity (P<0.05). Proliferation assay indicated that the proliferation rate of cells in each heat stress group was significantly decreased in comparison with normal control group 6h after heat stress (P<0.05). After 12h recovery, decrease in proliferation rate was observed only in 43℃ group (P<0.001), and no difference in the rate of proliferation could be observed between the heat stress groups and normal control group after 24h recovery. Flow cytometry showed, that the phagocytosis of KCs decreased in heat stress groups compared with control group, especially in 43℃ group (P<0.05). This phenomenon disappeared after 24h recovery. Conclusion Heat stress can inhibit the phagocytosis of rat liver KCs through its cytotoxic effect on KCs, and subsequently inhibits its proliferative ability. Further investigation of the effect of heat stress on KCs may help understand the pathogenesis of heat stress.

Objective To study the change of the contractile response of human umbilical artery smooth muscle cells (HUASMCs) during the heat stress, and explore the effect of the antioxidant on the changes. Methods HUASMCs were randomly divided into control group, heat stress group, antioxidant preprocessing group. Cells were stimulated by norepinephrine (NE) at a low concentration (0.05mg/L) and at a normal concentration (1.0mg/L) and cultured in the thermostatic water bath (41℃) for 0.5, 1, 1.5 or 2h, respectively. After stimulated by NE, proportion of the cell surface area contraction was measured to reflect the contractile response of each group. Results Compared with control group, regardless of the NE concentration: in heat stress group, contractile response at 1h increased significantly (P<0.05), while at 2h, it was reduced significantly (P<0.05 or 0.01). In the antioxidant preprocessing group, the contractile response was reduced significantly from heat stress to 2h after heat stress (P<0.05 or 0.01). There was no statistically significant difference in contractile response between different NE concentrations in the control group and heat stress group (P>0.05), but in the antioxidant preprocessing group, the contractile response was more significant to the normal NE concentration than to the low NE concentration (P<0.05 or 0.01). Regardless of the NE concentration, the contractile response was lower in the antioxidant preprocessing group than in the heat stress group. Conclusions In the course of heat stress, the contractile response of HUASMCs presents as time-related change. The usage of antioxidant may correct the over-response of HUASMCs to NE in the early heat stress stage, but cannot correct the reduction of the contractile response in the middle and advanced stage.

With the global warming, the incidence of heat stroke was significantly higher than before. Severe heat stroke has a high mortality, high morbidity and consolidated central nervous system injury characteristics. The main features of severe heat stroke cerebral injury include cognitive impairment, delirium, convulsions and coma. Its mechanism is related with heat shock induced cerebral tissue ischemia and hypoxia, vascular dysfunction, secondary cascade inflammation and so on. Currently, the main treatment of heat stroke cerebral injury is the hypothermia therapy, dehydration for the reduction of intracranial pressure, naloxone and other cerebral protection and nutrition treatments. Hyperbaric oxygen therapy (HBOT) is effective in treating brain injury. HBOT can alleviate tissue ischemia and hypoxia, improve circulation, reduce cerebral edema, and anti-inflammatory, anti-oxidative damage, anti-apoptosis and other molecular biological effects. HBOT also play a wake up-promoting effect of nerve repair in the cerebral injury. The treatment of cerebral injury has been the difficulty and weakness of heat stroke research. Therefore, this article reviewed the epidemiology, pathogenesis, the therapeutic effect and mechanism of hyperbaric oxygen on cerebral injury in severe heat stroke to clarify the advantages of HBOT and to provide experimental basis for further research.

Objective: To observe the effect of the outer orbicularis muscle partial resection combined with orbital fat flap or orbicularis muscle flap transfer to block orbicularis muscle for improvement of crow′s feet. Methods: From October 2010 to May 2015, 82 cases of females (aged from 27 to 54 years old) with crow′s feet were treated with new method(n=41) and traditional method(control, n=41). The new method included partial resection and orbital fat flap or orbicularis muscle flap transfer to block orbicularis muscle. The traditional method was performed to lift the skin and orbicularis oculi muscle to improve the crow′s feet. The operation time, the postoperative recovery time, eyes closing function and hematoma, nerve injury and other complications were recorded. 1, 3, 6 and 12 months after operation, the effect was assessed by one cosmetic surgeon who is unkown the groups. Completely correction was assed as 5 points and no improvement or even worse as 0 point. 12 months after operation, the patients satisfactory rate was recorded. Results: 75 cases were followed up, including 39 in new method group and 36 in control group. The operative time and postoperative recovery time were (50±5) min, (58±4) min and (5±1) d, (6.0±1.5) d in the new method group and control group respectively (P<0.05). The two groups both had good eyes closing function, no eyes closing fatigue or difficult or other serious complications such as hematoma, nerve injury. Visual analog scale were 3.2±0.6, 3.5±0.5, 4.2±0.8, 4.3±0.8 and 3.1±0.6, 3.4±0.9, 3.0±0.6, 2.8±0.5 in the new method group and control group at 1, 3, 6, 12 months after surgery respectively . Obviously, the effect in new method group was much better than that in control group after 6 and 12 months with statistical significance (P<0.05). 12 months after surgery, the satisfaction surveys showed satisfactory in 33 cases; fairly satisfactory in 4 cases; dissatisfactory in 2 cases in new method group, and satisfactory in 10 cases; fairly satisfactory in 15 cases; dissatisfactory in 11 cases in the control group, showing significant difference between the 2 groups (P<0.05). Conclusions The outer orbital orbicularis muscle partial resection combined with orbital fat flap or orbicularis muscle flap is reasonable and reliable to correct crow′s feet with short recovery and less complication. It is a worthy new method for recommendation.

Objective To investigate the effect of mitogen-activated protein kinases (MAPKs) activation on the heat stressinduced apoptosis of pulmonary microvascular endothelial cells (PMVECs).Methods A mouse model of severe heat stroke was made and TUNEL and immunohistochemistry were employed to detect lung tissue damage.MACS separation was used for isolation of neonatal PMVECs,and TUNEL was utilized to detect the apoptosis of PMVECs.Western blotting was used for determining the MAPKs activation during heat stress recovery (0,2,6h).The monolayer permeability of endothelial cells was detected in terms of transmembrane resistance (TEER) and horseradish peroxidase (HRP).Cells were pretreated with MAPKs activation inhibitors to examine the effect of heat stress on the monolayer cell permeability and apoptosis.Results In mice with severe heat stroke,extensive apoptosis of PMVECs was found in their pulmonary tissues.TUNEL revealed that the number of apoptotic cells increased over time during heat stress recovery period and heat stress could activate MAPKs in PMVECs.Compared with heat stress group,in the cells pretreated with p38 or ERK activation inhibitor PD98059 and SB203580,the monolayer permeability and apoptosis increased while in cells pretreated withJNK inhibitor SP600125,the cellular permeability and apoptosis decreased.Conclusion In mice with severe heat stoke,PMVECs might experience apoptosis and p38 and ERK could inhibit apoptosis while JNK could promote apoptosis.