Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Disease burden and mortality forecast of prostate cancer in Wuhan in 2010-2019 / 公共卫生与预防医学

Objective To analyze the data of prostate cancer in Wuhan from 2010 to 2019, understand the characteristics and trends of incidence, mortality, and YLL, and provide decision-making basis for Wuhan's cancer prevention and control strategies. Methods Data on deaths and incident cases of prostate cancer in Wuhan from 2010 to 2019 and from 2013 to 2017, respectively, were collected from the Wuhan Death Monitoring System. Indicators such as incidence rate, mortality rate, and years of life lost due to premature death (YLL) of prostate cancer in Wuhan were calculated using Excel 2016 and Python. The Bayesian Age-Period-Cohort Model (BAPC) was used to predict the mortality rate of prostate cancer in Wuhan from 2020 to 2024. The trend changes were described using the annual average percentage change (AAPC). Results From 2010 to 2019, the incidence, mortality, and YLL rates of prostate cancer in Wuhan showed an overall increasing trend (AAPC >0, P <0.05). The standardized mortality and incidence rates in the central urban area were significantly higher than those in the outer urban area, and the age group of 85 and above had the highest incidence and mortality rates. The age group of 0-54 had the largest increase in incidence and mortality rates. From 2020 to 2024, prostate cancer in Wuhan is expected to continue to increase slightly (an increase of 0.94%). Conclusion The incidence, mortality, and YLL rates of prostate cancer in Wuhan are showing an overall increasing trend, and this trend may continue. The characteristics are higher in the central urban area than in the outer urban area, and higher in the older age group than in the younger age group. Targeted measures need to be taken, and screening for high-risk populations should be strengthened.

Primary repair for concurrent bilateral intertrochanteric fracture and femoral head necrosis with prolonged shank biologic total hip replacement: A case report and surgical techniques / 中华创伤杂志(英文版)

For the treatment of an intertrochanteric fracture combined with femoral head necrosis in middle-age patients, it has been controversial whether to perform fracture reduction and fixation first then total hip replacement, or direct total hip replacement. We present a rare case of 53-year-old male patient suffered from bilateral intertrochanteric fracture caused by a road traffic injury. The patient had a history of femoral head necrosis for eight years, and the Harris score was 30. We performed total hip replacement with prolonged biologic shank prostheses for primary repair. One year after the surgery, nearly full range of motion was achieved without instability (active flexion angle of 110°, extension angle of 20°, adduction angle of 40°, abduction angle of 40°, internal rotation angle of 25°, and external rotation angle of 40°). The Harris score was 85. For the middle-aged patient with unstable intertrochanteric fractures and osteonecrosis of the femoral head, we can choose primary repair for concurrent bilateral intertrochanteric fracture and femoral head necrosis with prolonged shank biologic total hip replacement.

Study on long-acting analgesic lappaconitine hydrobromide lyotropic liquid crystal injection / 药学学报

Long-acting analgesia is a common clinical treatment method after surgery. The slow-release injection with long-acting analgesia has the advantages of less medication frequency and stable effect. In this study, the analgesic drug lappaconitine hydrobromide lyotropic liquid crystal injection was prepared, and its sustained release mechanism, drug release and pharmacodynamic characteristics were evaluated. The results of polarizing microscope and freeze-transmission electron microscope showed that the lyotropic liquid crystal injection of the liquid crystal precursor preparation of lappaconitine hydrobromide could be obtained by the combination of glycerol monooleate (GMO) and soybean lecithin (SPC) in different proportions. The results of dissolution study in vitro showed that the drug release rate of different forms of liquid crystal preparations was layered liquid crystal > cubic liquid crystal > hexagonal liquid crystal. The mathematical model fitting results of the release data showed that the external release of layered liquid crystal, cubic liquid crystal and hexagonal liquid crystal conforms to the Ritger-Peppas model, and the release mechanism was Fick diffusion. The results of pharmacodynamics study in vivo showed that the analgesic effect of lappaconitine hydrobromide lyotropic liquid crystal injection lasted for 3 days, and there was no abnormality in the incision and local tissue, showing good safety and tolerance. The study on drug release and elimination process of the in vivo gel repository showed that lappaconitine hydrobromide could be completely released from the lyotropic liquid crystal 3 days after administration, and the sustained-release materials could be gradually eliminated locally. All animal experiments were approved by the Experimental Animal Ethics Committee of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences (No. 2021-08-GY-61) and the experiments were conducted in accordance with the relevant guiding principles and regulations. The lyotropic liquid crystal injection of lappaconitine hydrobromide prepared in this study presented a solution state at room temperature, and underwent phase transition in contact with the body fluid at the administration site, formed a drug depot and exerted a slow drug release effect. This preparation can reduce systemic toxicity, prolong the duration of analgesia, reduce the number of administrations, improve the compliance of postoperative patients, and provide a reference for the design of long-term sustained release analgesic preparations.

Current status and trend analysis of breast cancer incidence and mortality in Wuhan / 公共卫生与预防医学

Objective To assess the prevalence of female breast cancer in the city using data from the Wuhan Disease and Cause of Death Surveillance System for the past 10 years to provide a reference for breast cancer prevention and control. Methods The incidence case data from 2013 to 2017 and death case data from 2010 to 2019 in all districts of Wuhan city were collected. The incidence and mortality and their age-standardized rates were calculated. The joinpoint linear regression model was used to analyze the average annual percentage change (AAPC) , and the Bayesian age-period-cohort model (BAPC) was used to predict the mortality and age-standardized mortality of breast cancer among women in Wuhan from 2020 to 2024. Results The incidence and age-standardized incidence were 56.56/100 000 and 45.37/100 000 in 2013, and 67.46/100 000 and 52.01/100 000 in 2017, respectively. The changes showed an upward trend, but the difference was not statistically significant (P>0.05). The mortality and age-standardized mortality were 9.80/100 000 and 8.07/100 000 in 2010, and 10.47/100 000 and 7.13/100 000 in 2019, respectively. Although the rough mortality increased, the age-standardization mortality declined significantly (AAPC=2.13%, P<0.05). BAPC prediction results show that the standardized mortality rate of female breast cancer in Wuhan will drop to 6.33/100 000 in 2024. The peak age of incidence was in the age groups of 45-74 years and the peak age of mortality was in the age group of 85 years or older. In addition , the morbidity and mortality rates in the central urban area were higher than those in the distant urban area , and the difference decreased year by year. The BAPC predicted that the age-standardized mortality for breast cancer in women in Wuhan will decrease to 6.33 per 100 000 in 2024. Conclusion Breast cancer incidence and mortality rates in females in Wuhan show an increasing trend . However , the age-standardized mortality is on a significant downward trend due to the delay in the age of death. The elderly and those in central urban areas are the high-risk groups, so we should pay more attention to these groups , analyze the related risk factors , and take targeted prevention and control measures.

Therapeutic Efficacy of Shexiang Baoxin Pill Combined with Exercise in Patients with Heart Failure with Preserved Ejection Fraction: A Single-Center, Double-Blind, Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the therapeutic efficacy of Shexiang Baoxin Pill combined with exercise in heart failure patients with preserved ejection fraction (HFpEF).@*METHODS@#Sixty patients with HFpEF were randomly divided into group A (n=20), receiving Shexiang Baoxin Pill combined with home-based exercise training based on conventional drugs for 12 weeks; group B (n=20), receiving conventional drugs combined with home-based exercise training for 12 weeks; and group C (n=20), receiving conventional drug treatment only. Peak oxygen uptake (peakVO2), anaerobic threshold (AT), 6-min walking test (6MWT), Pittsburgh Sleep Quality Index (PSQI), and SF-36 questionnaire (SF-36) results before and after treatment were compared among groups.@*RESULTS@#After the 12-week intervention, patients in group C showed significant declines in peakVO2, AT, 6MWT, PSQI, and SF-36 compared with pre-treatment (P<0.01), while groups A and B both showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 results compared with pre-treatment (P<0.01). Compared with group C, patients in groups A and B showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 (P<0.01). In addition, patients in group A showed more significant improvements in physical function, role-physical, vitality, and mental health scores on the SF-36 questionnaire, and PSQI scores than those in group B (P<0.01).@*CONCLUSIONS@#Exercise training improved exercise tolerance, sleep quality and quality of life (QoL) in patients with HFpEF. Notably, Shexiang Baoxin Pill played an active role in sleep quality and QoL of patients with HFpEF. (The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100054322)).

Recent research on extracorporeal carbon dioxide removal / 中国当代儿科杂志

Extracorporeal carbon dioxide removal is an artificial lung auxiliary technique based on extrapulmonary gas exchange and can effectively remove carbon dioxide and provide oxygenation to a certain extent, and it is one of the effective treatment techniques for hypercapnia developed after mechanical ventilation and extracorporeal membrane oxygenation in recent years and has wide application prospect. This article elaborates on the development, working principle, advantages, classification, complications, and clinical application of extracorporeal carbon dioxide removal, so as to provide a new choice for extracorporeal carbon dioxide removal in clinical practice.

Investigation of familial tendency of endometriosis / 中华妇产科杂志

Objective: To investigate the familial heritability of endometriosis and to compare the clinical characteristics of patients with or without a family history of endometriosis. Methods: From January 2020 to June 2022, 850 patients with endometriosis confirmed by laparotomy or laparoscopy in Peking University Third Hospital were included in this study. Clinical data were collected, family history was followed up, and the differences of clinical indicators between patients with and without family history of endometriosis were compared. Results: A total of 850 patients were enrolled, with an average age of (33.8±7.0) years old, 315 (37.1%, 315/850) patients in stage Ⅲ and 496 (58.4%, 496/850) patients in stage Ⅳ. There were 100 patients with family history of endometriosis, accounting for 11.8% (100/850). Most of the 113 relatives involved were mothers, daughters and sisters (76.1%, 86/113), 81.5% (22/27) of the second and third degree relatives were maternal relatives. The median ages of patients with and without family history of endometriosis were 30 and 33 years old respectively at the time of diagnosis. The unmarried rate of patients with family history was higher [42.0% (42/100) vs 26.3% (197/750)]. The percentage of dysmenorrhea patients with family history was higher [89.0% (89/100) vs 55.5% (416/750)]. The medians of dysmenorrhea score in patients with and without family history were 6 and 2, and the median durations of dysmenorrhea were 10 and 1 years. There were significant differences in age, marital status, percentage of dysmenorrhea, dysmenorrhea score and duration (all P<0.001). The median levels of serum cancer antigen (CA) 125 in patients with family history and patients without family history at the time of diagnosis were 57.5 and 46.9 kU/L respectively, with a statistically significant difference (P<0.05). However, there were no significant differences between the two groups in nationality, bady mass index, menarche age, menstrual cycle, menstrual period, menstrual volume, serum CA19-9 level, cyst location and size, stage, history of adverse pregnancy and childbirth, infertility, adenomyosis and deep infiltrating endometriosis (all P>0.05). By comparing the specific conditions of dysmenorrhea patients with and without family history of endometriosis, there were no significant differences between the two groups in terms of the age of onset of dysmenorrhea, duration of dysmenorrhea, primary and secondary dysmenorrhea, and progressive aggravation of dysmenorrhea (all P>0.05). The difference in the degree of dysmenorrhea in dysmenorrhea patients with family history of endometriosis was significant (P<0.001). Conclusions: The incidence of endometriosis has a familial tendency, and most of the involved relatives are the first degree relatives. Compared with patients without family history of endometriosis, endometriosis patients with family history are diagnosed at an earlier age, with higher percentage of dysmenorrhea, had more severe dysmenorrhea and higher serum CA125 level.

Analysis of the relationship between MRI imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients / 中华妇产科杂志

Objective: To investigate the relationship between magnetic resonance imaging (MRI) imaging characteristics and clinical symptoms and therapeutic efficacy in adenomyosis patients. Methods: The clinical characteristics of the adenomyosis questionnaire was self-designed. This was a retrospective study. From September 2015 to September 2020, totally 459 patients were diagnosed with adenomyosis and underwent pelvic MRI examination at Peking University Third Hospital. Clinical characteristics and treatment were collected, MRI was used to determine the lesion location, and to measure the maximum lesion thickness, the maximum myometrium thickness, uterine cavity length, uterine volume, the minimum distance between the lesion and serosa or endometrium, and whether combined with ovarian endometrioma. The difference of MRI imaging characteristics in patients with adenomyosis and its relationship with clinical symptoms and therapeutic efficacy were analyzed. Results: (1) Among the 459 patients, the age was (39.1±6.4) years. There were 376 patients (81.9%, 376/459) with dysmenorrhea. Whether patients had dysmenorrhea were related to uterine cavity length, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness, and whether patients had ovarian endometrioma (all P<0.001). Multivariate analysis suggested that ovarian endometrioma was the risk factor for dysmenorrhea (OR=0.438, 95%CI: 0.226-0.850, P=0.015). There were 195 patients (42.5%, 195/459) with menorrhagia. Whether patients had menorrhagia were related to age, whether patients had ovarian endometrioma, uterine cavity length, the minimum distance between lesion and endometrium or serosa, uterine volume, ratio of the maximum lesion thickness to the maximum myometrium thickness (all P<0.001). Multivariate analysis suggested that ratio of the maximum lesion thickness to the maximum myometrium thickness was the risk factor for menorrhagia (OR=774.791, 95%CI: 3.500-1.715×105, P=0.016). There were 145 patients (31.6%, 145/459) with infertility. Whether the patients had infertility were related to age, the minimum distance between lesion and endometrium or serosa, and whether patients had ovarian endometrioma (all P<0.01). Multivariate analysis suggested that young and large uterine volume were risk factors for infertility (OR=0.845, 95%CI: 0.809-0.882, P<0.001; OR=1.001, 95%CI: 1.000-1.002, P=0.009). (2) The success rate of in vitro fertilization-embryo transfer (IVF-ET) was 39.2% (20/51). Dysmenorrhea, high maximum visual analogue scale score and large uterine volume affected the success rate of IVF-ET (all P<0.05). The smaller the maximum lesion thickness, the smaller the distance between the lesion and serosa, the larger the distance between the lesion and endometrium, the smaller the uterine volume, and the smaller the ratio of the maximum lesion thickness to the maximum myometrium thickness, the better the therapeutic efficacy of progesterones (all P<0.05). Conclusions: Concomitant ovarian endometrioma increases the risk of dysmenorrhea in patients with adenomyosis. The ratio of the maximum lesion thickness to the maximum myometrium thickness is an independent risk factor for menorrhagia. Young and large uterine volume may increase the risk of infertility. Severe dysmenorrhea and large uterine volume affect the success rate of IVF-ET. The therapeutic efficacy of progesterones is relatively better when the lesion is small and far away from the endometrium.

Establishment of a recombined mannose-binding lectin protein-magnetic beads-enriched binding recombinant enzyme-assisted polymerase chain reaction assay for Candida in blood samples / 中华流行病学杂志

Objective: To establish a nested recombinant enzyme-assisted polymerase chain reaction (RAP) technique combined with recombined mannose-binding lectin protein (M1 protein)-magnetic beads enrichment for the detection of Candida albicans (C. albicans) and Candida tropicalis (C. tropicalis) in blood samples for the early diagnosis of candidemia albicans and candidiemia tropicalis. Methods: The primer probes for highly conserved regions of the internal transcribed spacerregions of C. albicans and C. tropicalis were deigned to establish RAP assays for the detections of C. albicans and C. tropicalis; The sensitivity and reproducibility of nucleic acid tests with gradient dilutions of standard strains and specificity of nucleic acid tests with common clinical pathogens causing bloodstream infection were condcuted. M1 protein-magnetic bead enriched plasma C. albicans and C. tropicalis were used for RAP and PCR in with simulated samples and the results were compared. Results: The sensitivity of the established dual RAP assay was 2.4-2.8 copies/reaction, with higher reproducibility and specificity. M1 protein-magnetic bead enrichment of pathogen combined with the dual RAP assay could complete the detections of C. albicans and C. tropicalis in plasma within 4 hours. Fie the pathogen samples at concentration <10 CFU/ml, the number of the samples tested by RAP was higher than that tested by PCR after enrichment. Conclusion: In this study, a dual RAP assay for the detections of C. albicans and C. tropicalis in blood sample was developed, which has the advantages of accuracy, rapidity, and less contaminants and has great potential for rapid detection of Candidemia.

Optic cup and disc segmentation model based on linear attention and dual attention / 生物医学工程学杂志

Glaucoma is one of blind causing diseases. The cup-to-disc ratio is the main basis for glaucoma screening. Therefore, it is of great significance to precisely segment the optic cup and disc. In this article, an optic cup and disc segmentation model based on the linear attention and dual attention is proposed. Firstly, the region of interest is located and cropped according to the characteristics of the optic disc. Secondly, linear attention residual network-34 (ResNet-34) is introduced as a feature extraction network. Finally, channel and spatial dual attention weights are generated by the linear attention output features, which are used to calibrate feature map in the decoder to obtain the optic cup and disc segmentation image. Experimental results show that the intersection over union of the optic disc and cup in Retinal Image Dataset for Optic Nerve Head Segmentation (DRISHTI-GS) dataset are 0.962 3 and 0.856 4, respectively, and the intersection over union of the optic disc and cup in retinal image database for optic nerve evaluation (RIM-ONE-V3) are 0.956 3 and 0.784 4, respectively. The proposed model is better than the comparison algorithm and has certain medical value in the early screening of glaucoma. In addition, this article uses knowledge distillation technology to generate two smaller models, which is beneficial to apply the models to embedded device.

Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway / 中国中药杂志

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.

Effect of Yunkang Oral Solution on pregnant mice with spleen deficiency syndrome / 中国中药杂志

This study aimed to investigate the therapeutic effect of Yunkang Oral Solution on the improvement of spleen deficiency and pregnancy outcomes in pregnant mice with spleen deficiency syndrome induced by irregular diet and over consumption of cold and bitter foods. To simulate human irregular diet and over consumption of cold and bitter foods leading to spleen deficiency, the pregnant mice with spleen deficiency syndrome were prepared using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, spleen deficiency-related indicators and diarrhea-related parameters were measured. Gastric and intestinal motility(gastric emptying rate and intestinal propulsion rate) were evaluated. The levels of serum ghrelin, growth hormone(GH), gastrin(Gas), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-c), chorionic gonadotropin β(β-CG), progesterone(P), and estradiol(E_2) were measured. Intestinal barrier function in pregnant mice with spleen deficiency syndrome was assessed. Conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length were calculated. The results showed that Yunkang Oral Solution significantly improved spleen deficiency-related indicators and diarrhea in pregnant mice with spleen deficiency syndrome, increased gastric emptying rate and intestinal propulsion rate, elevated the levels of gastrointestinal hormones(ghrelin, GH, and Gas) in the serum, and reduced lipid levels(TC and LDL-c), thereby improving lipid metabolism disorders. It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin and claudin-1 in colonic tissues, thereby alleviating intestinal barrier damage. Yunkang Oral Solution also regulated the levels of pregnancy hormones(β-CG, P, and E_2) in the serum of pregnant mice with spleen deficiency syndrome. Moreover, it increased the conception rate, ovarian coefficient, litter-bearing uterine coefficient, number of live fetuses, average fetal weight, and fetal length. These findings suggest that Yunkang Oral Solution can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.

Characteristics of digestive system symptoms and abdominal computed tomography imaging of patients infected with severe acute respiratory syndrome coronavirus 2 Omicron variant / 中华消化杂志

Objective:To investigate the characteristics of digestive system symptoms and its relation with the time of nucleic acid continuous positive in population infected with severe acute respiratory syndrome coronavirus 2 Omicron variant, and to analyze the abdominal computed tomography (CT) features of patients infected with Omicron variant.Methods:From April 11 to May 23, 2022, a questionnaire survey was conducted in patients infected with Omicron variant admitted to the Shanghai National Convention and Exhibition Center Fangcang Hospital. The questionnaire included basic information, the start time of nucleic acid positive, respiratory symptoms, digestive system syptoms and outcomes, etc.Combined with the clinical data, the relation between digestive tract symptoms and the time of nucleic acid continuous positive were analyzed. Thoracic and abdominal CT were performed for patients with continuous positive nucleic acid results ≥10 d, and the relationship between the abdominal CT imaging characteristics and the time of nucleic acid continuous positive was analyzed. Independent sample t-test and multivariate logistic regression were used for statistical analysis. Results:A total of 4 360 valid questionnaires were collected, including 2 475 males and 1 885 females, with a hospital stay of (6.8±4.9) d. Among the 4 360 patients, 1 979 patients (45.4%) had gastrointestinal symptoms such as loss of appetite, abdominal discomfort or pain, constipation and diarrhea. The time of nucleic acid continuous positive in patients with gastrointestinal symptoms was (7.4±5.5) d, which was longer than that of patients without gastrointestinal symptoms (6.5±3.6) d, and the difference was statistically significant ( t=3.78, P<0.001). During the isolation period in the Fangcang Hospital, the time of nucleic acid continuous positive in patients with complete remission of digestive tract symptoms was shorter than that of patients with no remission of digestive tract symptoms ((7.3±5.2) d vs. (8.5±5.7) d), and the difference was statistically significant ( t=2.25, P=0.025). The results of multivariate logistic regression analysis showed that the combination of gastrointestinal symptoms was an independent risk factor for continuous positive nucleic acid result ≥10 d ( OR=1.316, 95% confidence interval 1.294 to 2.205, P=0.046). Among the 299 patients with continuous positive nucleic acid results≥10 d, 187 cases (62.5%) had gastrointestinal symptoms, and 146 cases (48.8%) had abdominal CT findings of thickening of the gastroduodenal wall, thickening of the small intestinal wall, indistinct mesenteric vessels of the small intestine, and dilatation and pneumatosis of the colon. In patients with continuous positive nucleic acid results ≥10 d, abdominal CT indicated that patients with gastrointestinal imaging changes had a longer time of nucleic acid continuous positive than those without gastrointestinal imaging changes ((16.0±2.8) d vs. (13.0±2.1) d), and the difference was statistically significant ( t=2.62, P=0.009). Conclusions:Digestive system symptoms are common in patients infected with Omicron variant. The time of nucleic acid continuous positive in patients with gastrointestinal symptoms is longer than those without gastrointestinal symptoms. Some patients may have gastrointestinal lesions on abdominal CT.

Study on the mechanism of miRNA-20a in regulating lipopolysaccharide-induced pyroptosis and inflammation of A549 cells / 中国新生儿科杂志

Methods:Cultured human alveolar epithelial A549 cells were assigned into LPS group and blank control group. LPS group was stimulated with LPS and adenosine triphosphate to induce pyroptosis and inflammation. A549 cells were divided into 4 groups: miR-20a mimics group, mimics-negative control (NC) group, inhibitor group and inhibitor-NC group. MiRNA-20a mimics, mimics-NC, inhibitor, and inhibitor-NC were transfected respectively into A549 cells, and after 24 h, the cells were collected to verify transfection efficiency by qPCR. MiRNA-20a mimics and the constructed TLR4-3'UTR double luciferase reporter plasmid were co-transfected into A549 cells, and luciferase activity was analyzed. MiRNA-20a mimics/inhibitors were transfected into A549 cells, and then the cells were stimulated by LPS for 8 h followed by adenosine triphosphate for 30 min. QPCR, Western Blot and ELISA were used to detect the expression of GSDMD, inflammatory factors (ASC, NLRP3, Caspase-1, IL-1β) and Signaling molecules (TLR4、NF-κB) in A549 cells at mRNA level and protein level. Immunofluorescence was used to detect the expression of TLR4 in the A549 cells and NF-κB in the nucleus of A549 cells after transfecting with miRNA-20a mimics/inhibitor.Results:The mRNA and protein expression of pyroptosis marker molecule (GSDMD) and inflammatory factors (ASC, NLRP3, Caspase-1, IL-1β) in A549 cells stimulated with LPS were significantly higher than those in the blank control group, and the differences were statistically significant ( P<0.05). The expression of miRNA-20 in the mimics group was significantly higher than that in the mimic-NC group ( P<0.05), while the expression of miRNA-20a in the inhibitor group was lower than that in the inhibitor-NC group ( P<0.01). The double luciferase reporter gene experiment showed that the relative fluorescence value of the co-transfection group for TLR4-3'UTR-WT and miRNA-20a mimics was significantly lower than the co-transfection group for TLR4-3'UTR-WT and miRNA-20a mimics-NC ( P<0.05). The mRNA and protein levels of pyroptosis marker molecule (GSDMD) , inflammatory factors (ASC, NLRP3, Caspase-1, IL-1β) and signaling molecules (TLR4, NF-κB) were decreased in the mimics group compared to the mimics-NC group, and increased in inhibitor group compared to inhibitor-NC group. Conclusions:miRNA-20a may inhibit LPS-induced pyroptosis and inflammation of A549 cells via TLR4/NF-κB signal pathway.Objetive:To explore the potential role of miRNA-20a in lipopolysaccharide (LPS) induced pyroptosis and inflamation of human alveolar epithelial A549 cells and its regulation mechanisim.

Effects of different hemostasis methods in laparoscopic ovarian cyst surgery on postoperative pain and sex hormone levels / 中华内分泌外科杂志

Objective:To study the effect of different hemostasis methods on postoperative pain and sex hormone levels in patients undergoing laparoscopic ovarian cystectomy.Methods:A total of 118 patients with ovarian cysts admitted to our hospital from Jun. 2018.6 to Aug. 2020 were collected and grouped by digital table method into electrocoagulation hemostasis group (59 cases, electrocoagulation hemostasis) and suture hemostasis group (59 cases, suture hemostasis). Pain at time points, serum inflammatory factors and sex hormone levels in the two groups were measured, and the incidence of complications was counted 12 weeks after surgery.Results:The VAS scores of suture hemostasis group at 6, 12 and 24 h after operation (3.33±0.93, 3.63±1.02, 3.01±0.94) were significantly lower than those of the electrocoagulation hemostasis group (4.16±1.05, 4.61±1.17, 3.72±1.05) ; there was no significant difference in serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels between the preoperative suture hemostasis group and the electrocoagulation hemostasis group. The serum levels of IL-6 and TNF-α in the group (37.64±4.82ng/L, 39.67±4.71ng/L) were lower than those in the electrocoagulation hemostasis group (45.96±5.25ng/L, 48.96±5.14ng/L) ( P<0.05) .) ; there was no significant difference in serum follicle-stimulating hormone (FSH), estradiol (E 2) or luteinizing hormone (LH) levels between preoperative electrocoagulation hemostasis group and suture hemostasis group ( P>0.05) ; There was no significant difference in the three indexes in the suture hemostasis group 3 months after operation compared with those before treatment ( P>0.05). The serum FSH and LH [ (6.59±0.91) mIU/ml, (5.24±0.77) mIU/ml] in the suture hemostasis group were lower than those in the electrocoagulation hemostasis group [ (7.39±1.02) mIU/m, (5.97±0.89) mIU/m], E 2 in suture hemostasis group [ (51.08±6.09) pg/ml] was higher than that in electrocoagulation hemostasis group [ (46.88±5.59) pg/ml] ( P<0.05). In terms of the complication rate at 3 months after operation, the suture hemostasis group (32.20%) was significantly lower than electrocoagulation hemostasis (13.56%) ( P<0.05). After 1 year of follow-up, the pregnancy success rate of the suture hemostasis group (72.88%) was significantly higher than that of the electrocoagulation hemostasis group (52.54%) ( P<0.05). There was no significant difference in pregnancy outcomes ( P>0.05) . Conclusions:Suture hemostasis in patients undergoing laparoscopic ovarian cystectomy is beneficial to relieve postoperative pain, improve postoperative inflammatory response, protect their ovarian function, avoid complications such as abnormal ovulation and excessive menstrual flow, and improve the success rate of pregnancy. The overall application effect is better than electrocoagulation hemostasis.

Optimization of ethanol reflux extraction process of Ziziphi Spinosae Semen- Schisandrae Sphenantherae Fructus based on network pharmacology combined with response surface methodology / 中国中药杂志

The present study optimized the ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair by network pharmacology and Box-Behnken method. Network pharmacology and molecular docking were used to screen out and verify the potential active components of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus, and the process evaluation indexes were determined in light of the components of the content determination under Ziziphi Spinosae Semen and Schisandrae Sphenantherae Fructus in the Chinese Pharmacopoeia(2020 edition). The analytic hierarchy process(AHP) was used to determine the weight coefficient of each component, and the comprehensive score was calculated as the process evaluation index. The ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus was optimized by the Box-Behnken method. The core components of the Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair were screened out as spinosin, jujuboside A, jujuboside B, schisandrin, schisandrol, schisandrin A, and schisandrin B. The optimal extraction conditions obtained by using the Box-Behnken method were listed below: extraction time of 90 min, ethanol volume fraction of 85%, and two times of extraction. Through network pharmacology and molecular docking, the process evaluation indexes were determined, and the optimized process was stable, which could provide an experimental basis for the production of preparations containing Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus.

Intestinal Cckbr-specific knockout mouse as a novel model of salt-sensitive hypertension via sodium over-absorption / 老年心脏病学杂志（英文版）

OBJECTIVES@#To investigate the value of CCKBRfl/fl villin-Cre mice as a mouse model of salt-sensitive hypertension (SSH).@*METHODS@#In the first part, 2-month-old CCKBRfl/fl villin-Cre mice (CKO) and control CCKBRfl/fl mice (WT) were fed with normal diet (0.4% NaCl) or high salt diet (4% NaCl), separately for 6 weeks. In the rescue study, one week of hydrochlorothiazide or saline injection were treated with the CKO mice fed high salt diet. The blood pressure, biochemical indexes, and the expression of small intestinal sodium transporters (NHE3, NKCC1, eNaC) was detected. The organ injury markers (MMP2/MMP9) and the histopathological changes of kidneys were observed, whereas the changes of duodenal sodium absorption were detected by small intestinal perfusion in vivo.@*RESULTS@#The CCKBRfl/fl villin-Cre mice with high salt intake exhibited high blood pressure, increased duodenal sodium absorption and urinary sodium excretion, and with renal injury. The protein expression of NHE3, NKCC1 and eNaC were also significant increase in the intestine of CKO-HS mice. Treatment with hydrochlorothiazide remarkably attenuated the elevated blood pressure by high salt absorption in the CCKBRfl/fl villin-Cre mice, but no significant histopathological changes were observed.@*CONCLUSIONS@#These results support a crucial role of intestinal Cckbr deficiency on SSH development and the diuretic antihypertension effect in CCKBRfl/fl villin-Cre mice. The CCKBRfl/fl villin-Cre mice with the high salt intake may serve as a stable model of salt-sensitive hypertensive induced by sodium overloading.

Mechanism of Mongolian drug Naru-3 in initiation of neuroinflammation of neuropathic pain from MMP9/IL-1β signaling pathway / 中国中药杂志

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.

Wheat TaMYB1A Negatively Regulates the Phenylpropanoid Pathway and Plant Height / 中国生物化学与分子生物学报

The phenylpropanoid pathway is one of the important pathways for synthesizing plant secondary metabolites, which can produce lignin, flavonoid, and sinapoylmalate. These compounds can not only affect the plant growth, development, and stress response, but also be used to produce perfume, pesticide, dye, medicine, feed, and biomass energy. R2R3-MYBs play important roles in regulating plant secondary metabolism, organ development, and in responding to environmental stresses. Wheat (Triticum aestivum L.) is an important food crop, but lots of straw will be produced accompanied by grain yields. Therefore, elucidating the function and regulatory mechanism of R2R3 MYBs of wheat is crucial for the effective utilization of the wheat straw. RT-PCR results showed that TaMYB1A was highly expressed in the wheat stems, and the GFP-TaMYB1A fusion protein was mainly localized in the nucleus of the N. benthamiana epidermal cells. TaMYB1A has transcriptional repressive activity in yeast cells. In this study, TaMYB1A-overexpressed transgenic Arabidopsis lines were generated to elucidate the effect of overexpression of TaMYB1A on the biosynthesis of lignin and flavonoid. Our results suggested that overexpression of TaMYB1A inhibited the plant height (P < 0. 05) and decreased the lignin (P < 0. 05) and flavonoid (P < 0. 05) biosynthesis of the transgenic Arabidopsis plants significantly. TaMYB1A could bind to the promoters of the Arabidopsis At4CL1, AtC4H, AtC3H, and AtCHS as well as the wheat Ta4CL1 and TaC4H1 revealed by yeast one-hybrid (Y1H) assasy, the transcriptional repressive effect of TaMYB1A on At4CL1, AtC4H, AtC3H, and AtCHS was confirmed by dual-luciferase reporter systems and also on Ta4CL1 and TaC4H1 by a genetic approach. Gene chip and quantitative RT-PCR (qRT-PCR) results showed that overexpression of TaMYB1A down-regulated the expression of most of the key genes involved in the phenylpropanoid metabolism and decreased the 4CL activity (P < 0. 05) of the transgenic Arabidopsis plants significantly. As suggested above, the wheat TaMYB1A belongs to the subgroup 4 R2R3 MYB transcription factors. TaMYB1A could bind to the promoters of the key genes involved in phenylpropanoid metabolism, repress their expression and negatively regulate the phenylpropanoid metabolism pathway and plant height.