Surveillance of echinococcosis in Bayingolin Mongol Autonomous Prefecture, Xinjiang Uygur Autonomous Region from 2017 to 2022 / 中国血吸虫病防治杂志

Objective To analyze the echinococcosis surveillance results in Bayingolin Mongol Autonomous Prefecture, Xinjiang Uygur Autonomous Region from 2017 to 2022, so as to provide insights into formulation of echinococcosis control measures in the prefecture. Methods Villagers were randomly sampled using a multistage sampling method from class I and II echinococcosis endemic counties in Bayingolin Mongolian Autonomous Prefecture from 2017 to 2022 for detection of human echinococcosis, while all patients undergoing ultrasound examinations in medical institutions in class III endemic counties received active echinococcosis screening. In addition, livestock in centralized slaughterhouses or slaughtering sites were screened for echinococcosis using the palpation and necropsy method, and fresh domestic dog feces samples were collected from randomly selected dog owners in each administrative village for detection of Echinococcus copro-antigen in domestic dogs. The trends in detection of human and livestock echinococcosis, detection of newly diagnosed human echinococcosis cases and detection of Echinococcus coproantigen in domestic dogs were analyzed in Bayingolin Mongol Autonomous Prefecture from 2017 to 2022. Results The mean detection rate of human echinococcosis was 0.13% (540/407 803) in Bayingolin Mongol Autonomous Prefecture from 2017 to 2022, which appeared a tendency towards a decline over years (χ2trend = 1 217.21, P < 0.001), and the highest detection of newly diagnosed echinococcosis cases was seen in Hejing County (0.28%, 191/67 865). The detection of livestock echinococcosis appeared a tendency towards a decline over years from 2017 to 2022 (χ2trend = 147.02, P < 0.001), with the highest detection rate seen in Hejing County (3.44%, 86/2 500), and the detection of Echinococcus copro-antigen in domestic dogs appeared a tendency towards a decline over years from 2017 to 2022 (χ2trend = 302.46, P < 0.001), with the highest detection rate in Qiemo County (2.74%, 118/4 313). Conclusions The detection of human and livestock echinococcosis and dog feces antigens Echinococcus copro-antigen in domestic dogs all appeared a tendency towards a decline in Bayingolin Mongol Autonomous Prefecture, Xinjiang Uygur Autonomous Region from 2017 to 2022; however, there is still a high echinococcosis transmission risk in local areas. Sustainable integrated echinococcosis control is required in Bayingolin Mongol Autonomous Prefecture.

Association of attention deficit hyperactivity disorder symptoms and bullying behavior in children / 中国学校卫生

Objective@#The association between school bullying and attention deficit hyperactivity disorder (ADHD) symptoms among students in primary schools and the moderating role of gender was explored to provide scientific evidence for the prevention and control of school bullying.@*Methods@#A total of 4 764 students from 2 primary schools in Wuhan were selected using the convenience sampling method in March 2023. The Olweus Bully/Victim Questionnaire and Strengths and Difficulties Questionnaire were used. A Pearson χ 2 test was used to compare differences in school bullying rates among children with and without ADHD symptoms. Pearson correlation analysis and Process 3.3 were used to analyse the association between ADHD symptoms, and school bullying behaviour and the moderating role of gender.@*Results@#The reported rate of bullying victims in primary schools was 24.2% and the rate of bullying perpetration was 3.8%. The rate of ADHD symptom detection among primary school students was 5.9%. ADHD symptoms were positively associated with bullying and bullying victim behaviour ( r =0.16, 0.27, P <0.01). Specifically, the association between ADHD symptoms and bullying behavior tended to be stronger among boys than girls ( β boy =0.17, t =11.13; β girl =0.07, t =4.11, P <0.01).@*Conclusions@#ADHD symptoms are an important factor influencing school bullying behaviors in students, and gender moderates the association. In the process of preventing and controlling school bullying, ADHD symptoms and gender differences should be emphasized and comprehensive interventions should be implemented.

Right-to-Left Displacement of an Airgun Lead Bullet after Transorbital Entry into the Skull Complicated by Posttraumatic Epilepsy : A Case Report

Penetrating head injury is a serious open cranial injury. In civilians, it is often caused by non-missile, low velocity flying objects that penetrate the skull through a weak cranial structure, forming intracranial foreign bodies. The intracranial foreign body can be displaced due to its special quality, shape, and location. In this paper, we report a rare case of right-to-left displacement of an airgun lead bullet after transorbital entry into the skull complicated by posttraumatic epilepsy, as a reminder to colleagues that intracranial metal foreign bodies maybe displaced intraoperatively. In addition, we have found that the presence of intracranial metallic foreign bodies may be a factor for the posttraumatic epilepsy, and their timely removal appears to be beneficial for epilepsy control.

Clinical efficacy and learning curve of robot-assisted thymectomy via subxiphoid approach / 中国胸心血管外科临床杂志

@#Objective     To explore the clinical efficacy and learning curve of robot-assisted thymectomy via subxiphoid approach. Methods    The clinical data of patients with robot-assisted thymectomy surgery via subxiphoid approach performed by the same surgical team in the Department of Thoracic Surgery of Shanghai Pulmonary Hospital from February 2021 to August 2022 were retrospectively analyzed. The cumulative sum (CUSUM) analysis and best fit curve were used to analyze the learning curve of this surgery. The general information and perioperative indicators of patients at different learning stages were compared to explore the impact of different learning stages on clinical efficacy of patients. Results    A total of 67 patients were enrolled, including 31 males and 36 females, aged 57.10 (54.60, 59.60) years. The operation time was 117.00 (87.00, 150.00) min. The best fitting equation of CUSUM learning curve was y=0.021 2x3–3.192 5x2 +120.17x–84.444 (x was the number of surgical cases), which had a high R2 value of 0.977 8, and the fitting curve reached the top at the 25th case. Based on this, the learning curve was divided into a learning period and a proficiency period. The operation time and intraoperative blood loss in the proficiency stage were significantly shorter or less than those in the learning stage (P<0.001), and there was no statistical difference in thoracic drainage time and volume between the two stages (P>0.05). Conclusion    The learning process of robot-assisted thymectomy via subxiphoid approach is safe, and this technique can be skillfully mastered after 25 cases.

The efficacy of the combination of radiofrequency ablation and endoscopic metal stent in the treatment of 44 patients with unresectable cholangiocarcinoma / 中华消化杂志

Objective:To explore the efficacy of the combination of radiofrequency ablation(RFA) and endoscopic metal stent in the treatment of patients with unresectable cholangiocarcinoma.Methods:From January 3, 2012 to June 30, 2019, at the Department of Endoscopic of the Third Affiliated Hospital of Naval Medical University, the clinical data of 44 patients with unresectable cholangiocarcinoma who were treated by the combination of RFA and endoscopic metal stent were retrospectively collected, which included age, gender, location of cholangiocarcinoma(hilar cholangiocarcinoma and distal cholangiocarcinoma), etc. Postoperative evaluation was conducted based on the follow-up, including clinical success rate, postoperative complication rate, time of stent patency and overall survival time (OS). The Kaplan-Meier method and log-rank test were used to analyze the difference of OS between patients with hilar cholangiocarcinoma and distal cholangiocarcinoma. Mann-Whitney U test was used for statistical analysis. Results:The age of the 44 patients with cholangiocarcinoma was (70.3±11.6) years old, with 20 males (45.5%). There were 22 patients (50.0%) with hilar cholangiocarcinoma and 22 patients (50.0%) with distal cholangiocarcinoma. The clinical success rate of 44 patients was 93.2%(41/44). A total of 5 patients(11.4%) had postoperative complications, which were all improved by appropriate treatment. The median time of follow-up of the 44 patient was 9.2 months(ranged from 3.1 to 57.6 months), the median time of stent patency was 7.0 months (ranged from 5.8 to 8.2 months). Thirty-two patients (72.7%) died during the follow-up, and the median OS was 10.9 months(ranged from 9.0 to 12.8 months). The median OS of patients with hilar cholangiocarcinoma was 7.8 months(ranged from 4.6 to 11.0 months) and that of patients with distal cholangiocarcinoma was 12.5 months(ranged from 5.7 to 19.4 months), and there was no statistically significant difference( P>0.05). Conclusion:RFA combined with endoscopic metal stent is safe and effective in the treatment of patients with unresectable cholangiocarcinoma.

Influence of effective liver drainage volume on overall survival in patients with malignant hilar biliary obstruction: a multicenter study / 中华消化内镜杂志

Objective:To investigate the influence of liver drainage volume on overall survival time in patients with unresectable malignant hilar bile duct obstruction.Methods:Data of 633 patients with unresectable malignant hilar bile duct obstruction (BismuthⅡ-Ⅳ) who underwent endoscopic stent drainage in 3 endoscopy centers from January 2002 to May 2019 were retrospectively analyzed. Main observation indicators included clinical success rate, stent patency, overall survival, the effective liver drainage volume, and complication incidence.Results:The clinical success rates of patients with liver drainage volume <30%, 30%-50%, and >50% were 56.8% (25/44), 77.3% (201/260) and 84.2% (277/329) respectively. The incidences of early cholangitis were 31.8% (14/44), 18.8% (49/260) and 16.1% (53/329). The median stent patency time was 4.5 (95% CI: 1.8-7.2) months, 5.6 (95% CI: 5.0-6.2) months and 6.6 (95% CI: 5.2-8.0) months. The overall survival time was 2.4 (95% CI: 1.8-3.0) months, 4.0 (95% CI: 3.4-4.6) months and 4.9 (95% CI:4.4-5.4) months, respectively. The clinical success rate ( χ 2=8.28, P=0.012), median stent patency period ( χ 2=18.87, P=0.015) and overall survival time ( χ 2=6.93, P=0.024) of 30%-50% liver drainage volume group were significantly higher than those of <30% group. Further multivariate cox regression analysis showed that the disease type (hepatocellular carcinoma VS hilar cholangiocarcinoma: HR=1.50, 95% CI:1.18-1.91, P=0.001; gallbladder carcinoma VS hilar cholangiocarcinoma: HR=1.45, 95% CI:1.14-1.85, P=0.002; metastatic cholangiocarcinoma VS hilar cholangiocarcinoma: HR=1.48, 95% CI:1.08-2.04, P=0.015), bilirubin level >200 μmol/L ( HR=1.35, 95% CI:1.14-1.60, P<0.001),metal stents ( HR=0.67, 95% CI:0.56-0.79, P<0.001), liver drainage volume (volume 30%-50% VS <30%: HR=0.64, 95% CI: 0.45-0.90, P=0.010; volume>50% VS <30%: HR=0.58, 95% CI:0.41-0.81, P=0.002) and anti-tumor therapy ( HR=0.51, 95% CI:0.42-0.61, P<0.001) were independent predictors for overall survival time of patients with unresectable malignant hilar bile duct obstruction. Conclusion:When endoscopic stent drainage is performed for patients with unresectable malignant hilar bile duct obstruction, at least 30% liver volume is required for better overall survival. In addition, the use of metal stent drainage and anti-tumor therapy may increase survival benefits.

Effect of early thoracic paracentesis drainage on acute lung injury in severe acute pancreatitis / 临床肝胆病杂志

Objective To investigate the effect of early thoracic paracentesis drainage for pleural effusion with a small or moderate volume on acute lung injury in patients with severe acute pancreatitis (SAP). Methods A retrospective analysis was performed for the clinical data of 107 patients with SAP who were admitted to The General Hospital of Western Theater Command from January 2015 to December 2021, and according to whether thoracic paracentesis drainage was performed within the first three days after admission, the patients were divided into thoracic paracentesis drainage group (TPD group with 51 patients) and non-thoracic paracentesis drainage group (N-TPD group with 56 patients).The two groups were compared in terms of laboratory markers and clinical outcome on days 5 and 10 after admission.The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Results Compared with the N-TPD group, the TPD group had a significantly shorter length of stay in the intensive care unit, a significantly shorter length of hospital stay, and significantly lower hospital costs (all P < 0.05), while there were no significant differences between the TPD group and the N-TPD group in mortality rate (9.8% vs 14.3%, χ 2 =0.502, P =0.478) and the incidence rate of sepsis (29.4% vs 44.6%, χ 2 =2.645, P =0.104).The TPD group had a significant reduction in the incidence rate of acute respiratory distress syndrome (ARDS)( χ 2 =6.038, P =0.043), as well as a significantly lower incidence rate of moderate ARDS than the N-TPD group (7.8% vs 21.4%, χ 2 =3.874, P =0.049).Compared with the N-TPD group, the TPD group had a significantly lower rate of use of mechanical ventilation (35.3% vs 57.2%, χ 2 =6.735, P =0.034) and a significantly lower proportion of patients receiving invasive mechanical ventilation (9.8% vs 26.8%, χ 2 =5.065, P =0.024).Compared with the N-TPD group, the TPD group had a significantly lower incidence rate of pulmonary infection (23.5% vs 42.9%, χ 2 =4.466, P =0.035) and a significantly shorter duration of systemic inflammatory response syndrome (11.2±5.0 days vs 16.8±4.7 days, t =5.949, P < 0.001).Compared with the N-TPD group, the TPD group had significantly better laboratory markers (high-sensitivity C-reactive protein, interleukin-1, interleukin-6, interleukin-8, tumor necrosis factor-α, arterial partial pressure of oxygen, oxygen saturation, and oxygenation index) and incidence rate of respiratory failure on days 5 and 10 after admission (all P < 0.05).On day 10 after admission, the TPD group had significantly better APACHE Ⅱ score and modified Mashall score than the N-TPD group (both P < 0.05). Conclusion For SAP patients with a small or moderate volume of pleural effusion, early thoracic paracentesis drainage can effectively improve acute lung injury, alleviate systemic inflammatory response, shorten the length of hospital stay, and reduce hospital costs.

Current research status of left-sided portal hypertension after superior mesenteric-portal vein confluence pancreaticoduodenectomy / 临床肝胆病杂志

Surgical operation is the main treatment method for pancreatic cancer, and in clinical practice, radical surgery for pancreatic cancer is often combined with superior mesenteric-portal vein confluence pancreaticoduodenectomy to achieve R0 resection. However, severe left-sided portal hypertension (LSPH) may occur after splenic vein dissection, resulting in a series of pathological changes such as congestive splenomegaly, thrombocytopenia, backflow obstruction of splenic vein, and gastrointestinal varices, and in some cases, it can lead to fatal gastrointestinal hemorrhage and hemorrhagic shock. Therefore, in order to better manage LSPH in clinical practice, this article systematically analyzes and reviews the pathogenesis, treatment regimens, and control strategies of LSPH after combined superior mesenteric-portal vein confluence pancreaticoduodenectomy and put forward corresponding suggestions based on current studies.

Severe Adverse Events of Periocular Acupuncture: A Review of Cases

Acupuncture is recognized as a component of alternative medicine and is increasingly used worldwide. Many studies have shown the various effects of acupuncture around the eyes for ophthalmologic or nonophthalmologic conditions. For ophthalmologic conditions, the effect of acupuncture on dry eye syndrome, glaucoma, myopia, amblyopia, ophthalmoplegia, allergic rhinoconjunctivitis, blepharospasm, and blepharoptosis has been reported. Recently, several studies on dry eye syndrome have been reported and are in the spotlight. However, given the variety of study designs and reported outcomes of periocular acupuncture, research is still inconclusive, and further studies are required. In addition, although a systematic and reliable safety assessment is required, to the best of our knowledge, there have been no reports of a literature review of ocular complications resulting from periocular acupuncture. This review collected cases of ocular injury as severe adverse events from previously published case reports of periocular acupuncture. A total of 14 case reports (15 eyes of 14 patients) of adverse events published between 1982 and 2020 were identified. This review article provides a summary of the reported cases and suggestions for the prevention and management of better visual function prognosis.

Application of nuclear magnetic resonance in the clinical study of high myopia / 国际眼科杂志(Guoji Yanke Zazhi)

Myopia is a harmful ophthalmic disease that may change the activity of the visual cortex and affect the corresponding neural function. At present, the incidence rate of myopia in China has been rising unprecedentedly, especially in high myopia(HM). Therefore, efficacious prevention and treatment of myopia are extremely important. However, since the specific pathogenesis of myopia has not been clarified so far, it is difficult to achieve the prevention and control of the disease at its source. Recently, there have been studies on the pathogenesis of myopia from the perspective of genetics, environment, neurotransmitters, etc., but few studies have explored the neuroimaging mechanism of myopia from the perspective of brain structure and function. With the development of magnetic resonance imaging(MRI)technology, brain images gradually appear in the study of myopia-related mechanisms. Therefore, this paper summarizes the research on myopia-related brain images, to provide an important reference for the clinical prevention and control of myopia.

Effects of arsenic exposure on E2 and TRH and their receptor mRNA expressions in rats / 环境与职业医学

Background Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. Objective To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. Methods Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg−1 sodium arsenite (NaAsO2)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO2 by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg−1 ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects. Conclusion Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.

In vitro bacteriostatic and serum pharmacological tests of Qiguiyin decoction combined with levofloxacin against pseudomonas aeruginosa / 中国药理学通报

Aim To investigate the antibacterial activity and anti-resistant mutation ability of Qiguiyin decoction (a traditional Chinese herbal formula) combined with levofloxacin against pseudomonas aeruginosa byantibacterial experiment in vitro and serum pharmacology. Methods The minimal inhibitory concentrations (MICs) of levofloxacin and Qiguiyin decoction were detected respectively by the broth dilution technique.The MIC of the combination of two drugs was determined by the micro chessboard dilution method. The effects of combined drugs on enhancing the antibacterial activity of different strains were evaluated respectively by calculating the fractional inhibitory concentration index (FICI). The drug-containing serum of levofloxa-cin group, Qiguiyin decoction group, Qiguiyin decoction combined with levofloxacin group and control group was prepared. The antibacterial rate, MIC and MBC of 10% ~ 90% serum against the two strains were determined. Results Combined with Qiguiyin decoction, MIC of levofloxacin against pseudomonas aeruginosa (standard/resistant) decreased significantly, 0. 5 < FICI

Research advances in acute pancreatitis-associated ascites fluid / 临床肝胆病杂志

Acute pancreatitis-associated ascites fluid (PAAF) is a common complication in patients with acute pancreatitis (AP) and is closely associated with the severity of AP, the development of local and systemic complications, and prognosis. PAAF may originate from the leakage of abdominal blood vessels, lymphatic vessels, and pancreatic duct. Recent studies have found that early removal of PAAF by abdominal paracentesis drainage can help to reduce systemic inflammation and alleviate pancreatitis-associated organ injury, thereby improving the conditions of patients with severe AP and reducing mortality. However, it is still not completely clear how PAAF aggravates systemic inflammatory response, participates in pancreatic injury and damage of distal organs, and leads to the aggravation of disease conditions in patients with AP. Therefore, this article gives an overview of PAAF and summarizes related studies in recent years, so as to provide directions for exploring the pathophysiological process and treatment of AP.

Rhodojaponin VI indirectly targets Cav2.2 channels via N-ethylmaleimide-sensitive fusion protein to alleviate neuropathic pain

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca2+ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.

Chemogenetic and Optogenetic Manipulations of Microglia in Chronic Pain / 神经科学通报·英文版

Chronic pain relief remains an unmet medical need. Current research points to a substantial contribution of glia-neuron interaction in its pathogenesis. Particularly, microglia play a crucial role in the development of chronic pain. To better understand the microglial contribution to chronic pain, specific regional and temporal manipulations of microglia are necessary. Recently, two new approaches have emerged that meet these demands. Chemogenetic tools allow the expression of designer receptors exclusively activated by designer drugs (DREADDs) specifically in microglia. Similarly, optogenetic tools allow for microglial manipulation via the activation of artificially expressed, light-sensitive proteins. Chemo- and optogenetic manipulations of microglia in vivo are powerful in interrogating microglial function in chronic pain. This review summarizes these emerging tools in studying the role of microglia in chronic pain and highlights their potential applications in microglia-related neurological disorders.

Leonurine inhibits ferroptosis in renal tubular epithelial cells by activating p62/Nrf2/HO-1 signaling pathway / 中国中药杂志

To investigate the protective effect and the potential mechanism of leonurine(Leo) against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells), an in vitro erastin-induced ferroptosis model was constructed to detect the cell viability as well as the expressions of ferroptosis-related indexes and signaling pathway-related proteins. HK-2 cells were cultured in vitro, and the effects of Leo on the viability of HK-2 cells at 10, 20, 40, 60, 80 and 100 μmol·L~(-1) were examined by CCK-8 assay to determine the safe dose range of Leo administration. A ferroptosis cell model was induced by erastin, a common ferroptosis inducer, and the appropriate concentrations were screened. CCK-8 assay was used to detect the effects of Leo(20, 40, 80 μmol·L~(-1)) and positive drug ferrostatin-1(Fer-1, 1, 2 μmol·L~(-1)) on the viability of ferroptosis model cells, and the changes of cell morphology were observed by phase contrast microscopy. Then, the optimal concentration of Leo was obtained by Western blot for nuclear factor erythroid 2-related factor 2(Nrf2) activation, and transmission electron microscope was further used to detect the characteristic microscopic morphological changes during ferroptosis. Flow cytometry was performed to detect reactive oxygen species(ROS), and the level of glutathione(GSH) was measured using a GSH assay kit. The expressions of glutathione peroxidase 4(GPX4), p62, and heme oxygenase 1(HO-1) in each group were quantified by Western blot. RESULTS:: showed that Leo had no side effects on the viability of normal HK-2 cells in the concentration range of 10-100 μmol·L~(-1). The viability of HK-2 cells decreased as the concentration of erastin increased, and 5 μmol·L~(-1) erastin significantly induced ferroptosis in the cells. Compared with the model group, Leo dose-dependently increased cell via-bility and improved cell morphology, and 80 μmol·L~(-1) Leo promoted the translocation of Nrf2 from the cytoplasm to the nucleus. Further studies revealed that Leo remarkably alleviated the characteristic microstructural damage of ferroptosis cells caused by erastin, inhibited the release of intracellular ROS, elevated GSH and GPX4, promoted the nuclear translocation of Nrf2, and significantly upregulated the expression of p62 and HO-1 proteins. In conclusion, Leo exerted a protective effect on erastin-induced ferroptosis in HK-2 cells, which might be associated with its anti-oxidative stress by activating p62/Nrf2/HO-1 signaling pathway.

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

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

Chemical constituents, pharmacological activities, processing and clinical application of traditional Chinese medicine Scrophulariae Radix: a review / 中国中药杂志

Traditional Chinese medicine Scrophulariae Radix, which is also called Yuan Shen, black Shen, is the dried root of Scrophularia ningpoensis of the Scrophulariaceae family. Research has indicated that the chemical constituents of Scrophulariae Radix mainly include terpenoids, phenylpropanoids, organic acids, volatile oils, steroids, sugars, flavonoids, alkaloids and phenols, among which iridoids and phenylpropanoids were the main active constituents. It has been reported that extracts of Scrophulariae Radix or its active substances have anti-inflammatory, antioxidant, hepatoprotective, anti-tumor, anti-fatigue, uric acid-lowering, anti-depression, myocardial cell-protective and other pharmacological activities, and can regulate cardiovascular system, central nervous system and immune system. This paper reviewed the present research achievements of Scrophulariae Radix in chemical constituents, pharmacological activities, processing methods, toxicity and other aspects, and the clinical application of Scrophulariae Radix in ancient and modern times was illustrated. This paper aimed to provide reference for further research of Scrophulariae Radix and facilitated its clinical application.

Expert consensus on late stage of critical care management / 中华内科杂志

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.

Lipid carriers for mRNA delivery

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.