Mediated Peroxymonosulfate Activation at the Single Atom Fe-N3 O1 Sites: Synergistic Degradation of Antibiotics by Two Non-Radical Pathways.

The activation of persulfates to degrade refractory organic pollutants is a hot issue in advanced oxidation right now. Here, it is reported that single-atom Fe-incorporated carbon nitride (Fe-CN-650) can effectively activate peroxymonosulfate (PMS) for sulfamethoxazole (SMX) removal. Through some characterization techniques and DFT calculation, it is proved that Fe single atoms in Fe-CN-650 exist mainly in the form of Fe-N3 O1 coordination, and Fe-N3 O1 exhibited better affinity for PMS than the traditional Fe-N4 structure. The degradation rate constant of SMX in the Fe-CN-650/PMS system reached 0.472 min-1 , and 90.80% of SMX can still be effectively degraded within 10 min after five consecutive recovery cycles. The radical quenching experiment and electrochemical analysis confirm that the pollutants are mainly degraded by two non-radical pathways through 1 O2 and Fe(IV)═O induced at the Fe-N3 O1 sites. In addition, the intermediate products of SMX degradation in the Fe-CN-650/PMS system show toxicity attenuation or non-toxicity. This study offers valuable insights into the design of carbon-based single-atom catalysts and provides a potential remediation technology for the optimum activation of PMS to disintegrate organic pollutants.

Application of proteomics technology in dry eye disease and acupuncture treatment / 国际眼科杂志(Guoji Yanke Zazhi)

Dry eye disease(DED)refers to a condition characterized by reduced stability of the tear film or an imbalance in the microenvironment of the ocular surface, resulting from abnormalities in quality, quantity and kinetics of tear. This condition leads to various ocular discomforts and even visual impairment. The pathogenesis of DED is multifactorial and current treatment mainly focuses on symptom relief and preservation of visual function. Acupuncture has shown effectiveness in treating dry eye, although its underlying mechanism remains incompletely understood. Proteomics technology offers a comprehensive and systematic approach to studying the functions, structures and interactions of proteins. Its application in DED research can provide valuable insights into the dynamic changes in protein levels associated with different etiology or the course of DED and facilitate the identification of potential biomarkers. Furthermore, proteomics can systematically explore the regulatory mechanisms underlying acupuncture treatment for DED, providing a theoretical basis for acupuncture treatment research and contributing to the understanding of its effects at a fundamental level. This paper aims to explore the potential application of proteomics in both clinical and basic research on DED. Ultimately, it strives to offer scientific and effective strategies for the diagnosis and treatment of DED and advance our knowledge of the mechanisms underlying acupuncture therapy.

Paraneoplastic anti-GAD65 extralimbic encephalitis presented with epilepsy: A case report.

RATIONALE: Autoimmunity targeting glutamic acid decarboxylase 65 (GAD65) is associated with type 1 diabetes mellitus as well as various neurological diseases. In the central nervous system, GAD65 autoimmunity usually presents with limbic encephalitis, whereas extralimbic encephalitis (ELE) has only been reported in a few cases. Moreover, anti-GAD65 ELE in the paraneoplastic context has not yet been reported. PATIENT CONCERNS: A 60-year-old man presented with intermittent cough and sputum for 10 years, with no other diseases. The patient presented with recurrent seizures that were resistant to antiepileptic drugs (AEDs). Chest computed tomography and pathological results confirmed the diagnosis of small cell lung cancer. Paraneoplastic testing found a high level of GAD65 antibodies in his serum, and cerebrospinal fluid analysis revealed lymphocytic pleocytosis, indicating autoimmune encephalitis. Brain magnetic resonance imaging showed multifocal T2 fluid-attenuated inversion recovery hyperintensities in the extralimbic areas including the subcortex and deep white matter of the bilateral frontal lobe, parietal lobe, and insula lobes. DIAGNOSES: Finally, a diagnosis of anti-GAD65 autoimmune ELE with a paraneoplastic etiology from the small cell lung cancer was suspected. INTERVENTIONS: The patient refused any tumor-suppressive treatment or immunotherapy for potential side effects and only received AEDs levetiracetam, sodium valproate, and diazepam. OUTCOMES: The epilepsy of the patient was resistant to AEDs, and the patient died a week after discharge due to disease progression. LESSONS: Anti-GAD65 autoimmune encephalitis can be extralimbic, can present with isolated epilepsy, and extralimbic anti-GAD65 encephalitis can occur with an underlying malignancy.

Association between maternal HIV infection and the risks of preterm birth and low birth weight in Chengdu, China: a propensity score matching approach.

OBJECTIVES: To estimate the effect of HIV infection on the risk of preterm birth (PTB) and low birth weight (LBW) among Chinese pregnancy women. DESIGN: A retrospective cohort study included HIV-positive pregnant women who gave birth to singletons in Chengdu between 2011 and 2020 and and HIV-negative pregnant women who delivered singletons at the Chengdu Women's and Children's Central Hospital in 2020. SETTING: Data of pregnant women living with HIV were extracted from China's Information System of Prevention of Mother-to-Child Transmission of HIV Management. Additionally, information for HIV-negative pregnant women was extracted from the electronic medical record system of the Chengdu Women's and Children's Central Hospital. PARTICIPANTS: 755 HIV-positive women and 15,094 HIV-negative pregnant women were included. PRIMARY OUTCOME MEASURES: PTB and LBW rates, which were defined by gestational weeks and birth weight. RESULTS: The incidences of PTB and LBW (13.51% and 14.17%, respectively) were significantly higher in the HIV-positive group compared with the HIV-negative group (6.82% and 4.65%). Propensity score matching was performed to improve comparability of the two groups, resulting in 1590 pregnancies with 558 HIV-positive and 1032 HIV-negative women in the final analysis. Conditional logistic regression was used to estimate the effect of maternal HIV status on adverse pregnancy outcomes. After propensity score matching and controlling the potential confounders, HIV infection was strongly associated with higher chances of LBW and PTB with adjusted odd ratios (95% confidence interval) of 2.53 (1.74 to 3.68) and 1.95 (1.33 to 2.85), respectively. CONCLUSIONS: HIV infection was significantly associated with increased risks of PTB and LBW in Chinese pregnant women. Future studies should focus on investigating the mechanisms underlying the association between HIV infection and adverse birth outcomes, and on identifying strategies to reduce the incidence of PTB and LBW in pregnant women living with HIV.

PET-based radiomics visualizes tumor-infiltrating CD8 T cell exhaustion to optimize radiotherapy/immunotherapy combination in mouse models of lung cancer.

BACKGROUND: Cumulative preclinical and clinical evidences showed radiotherapy might augment systemic antitumoral responses to immunotherapy for metastatic non-small cell lung cancer, but the optimal timing of combination is still unclear. The overall infiltration and exhausted subpopulations of tumor-infiltrating CD8+ T cells might be a potential biomarker indicating the response to immune checkpoint inhibitors (ICI), the alteration of which is previously uncharacterized during peri-irradiation period, while dynamic monitoring is unavailable via repeated biopsies in clinical practice. METHODS: Basing on tumor-bearing mice model, we investigated the dynamics of overall infiltration and exhausted subpopulations of CD8+ T cells after ablative irradiation. With the understanding of distinct metabolic characteristics accompanied with T cell exhaustion, we developed a PET radiomics approach to identify and visualize T cell exhaustion status. RESULTS: CD8+ T cell infiltration increased from 3 to 14 days after ablative irradiation while terminally exhausted populations significantly predominated CD8+ T cells during late course of this infiltrating period, indicating that 3-7 days post-irradiation might be a potential appropriate window for delivering ICI treatment. A PET radiomics approach was established to differentiate T cell exhaustion status, which fitted well in both ICI and irradiation settings. We also visualized the underlying association of more heterogeneous texture on PET images with progressed T cell exhaustion. CONCLUSIONS: We proposed a non-invasive imaging predictor which accurately assessed heterogeneous T cell exhaustion status relevant to ICI treatment and irradiation, and might serve as a promising solution to timely estimate immune-responsiveness of tumor microenvironment and the optimal timing of combined therapy.

Structure-performance correlation guided cerium-based metal-organic frameworks: Superior adsorbents for fluoride removal in water.

Fluoride in the hydrosphere exceeds the standard, which could be critically hazardous to human health and the natural environment. The adsorption method is a mature and effective way to remove pollutants in water, including fluoride. In this study, we synthesized three kinds of cerium-based metal-organic frameworks (Ce-MOFs) with different structures and properties by modulating the organic ligands (i.e., trimesic acid (BTC), 1,2,4,5-benzenetetracarboxylic acid (PMA), and terephthalic acid (BDC)) via the solvothermal method. The adsorption kinetics of Ce-MOFs on fluoride well fit the pseudo second order model, and their adsorption isotherms also conform to Langmuir isothermal model. The thermodynamic study reveals that the adsorption process is a spontaneous endothermic reaction. The maximum saturated adsorption capacities of Ce-BTC, Ce-PMA, and Ce-BDC are 70.7, 159.6, and 139.5 mg g-1, respectively. Ce-MOFs have stable and excellent adsorption capacity at pH = 3-9. Coexisting anions (Cl-, SO42-, and NO3-) do not affect the performance of Ce-MOFs for fluoride removal. Moreover, Ce-MOFs also show their broad prospect as superior fluoride adsorbents because of their excellent performance and reusability in real water samples. Organic ligands have a remarkable influence on the defluoridation performance of Ce-MOFs. This work will provide a feasible idea for designing MOFs as superiors adsorbents for defluoridation.

Single atom Mn anchored on N-doped porous carbon derived from spirulina for catalyzed peroxymonosulfate to degradation of emerging organic pollutants.

Highly efficient single atom catalysts are critical to substantially promote for peroxymonosulfate (PMS) activation to organic pollutant degradation, but it remains a challenge at present. Herein, single atom Mn anchored on N-doped porous carbon (SA-Mn-NSC) was synthesized by ball milling of Mn-doped carbon nitride and spirulina biochar to dominantly activate PMS. The precursor of carbon nitride and spirulina possessed a strong coordinating capability for Mn(II), facilitating the formation of highly dispersed nitrogen-coordinated Mn sites (Mn-N4). The SA-Mn-NSC catalyst exhibited high activity and stability in the heterogeneous activation of PMS to degrade a wide range of pollutants within 10 min, showing an outstanding degradation rate constant of 0.31 min-1 in enrofloxacin (ENR) degradation. The high surface density of Mn-N4 sites and abundant interconnected meso-macro pores were highly favorable for activating PMS to produce 1O2 and high-valent manganese (Mn(IV)) for pollutant degradation. This work offers a new pathway of using a low-cost and easily accessible single-atom catalysts (SACs) and could inspire more catalytic oxidation strategies.

Effect of needle-free jet injection of insulin glargine on glycaemic fluctuation in type 2 diabetic patients with uncontrolled glycemia / 中华内分泌代谢杂志

Objective:To investigate the effects of insulin glargine administration by jet injection versus conventional insulin pen on glucose profile using professional mode flash glucose monitoring(FGM) system in type 2 diabetic patients with poor glucose control.Methods:In this randomized, controlled, crossover study, 40 patients with T2DM who treated with insulin glargine were enrolled. The patients were randomly divided into group A(jet injector-conventional pen, n=20) and group B(conventional pen-jet injector, n=20). Each patient wore FreeStyle Libre sensor from day 4 to day 17. The specialist nurse instructed patients how to master the injection techniques. Professional FGM system was applied to assess glucose profile. Results:The fasting blood glucose(FBG) of the enrolled patients was(9.37±1.84) mmol/L. In contrast to conventional insulin pen, treatment with the jet injector significantly decreased the 24h MBG [(9.06±2.13 vs 9.98±2.67) mmol/L, P=0.001], MaxBG [(16.69±3.01 vs 17.95±3.48) mmol/L, P=0.001], AUC>10 mmol/L [95.93(21.12, 129.02) vs 142.66( 27.88, 198.46), P=0.002], TAR(31.10±21.89 vs 39.49±25.93, P=0.003), MAGE and SDBG. It was observed that patients using jet injector had significant increased TIR(65.94±20.47 vs 58.32±25.00, P=0.001). There were no difference in the risk of hypoglycaemia between two groups. Conclusion:Insulin jet injector was more effective than the insulin pen on glycaemic control and glucose fluctuation without increasing the risk of hypoglycemia in type 2 diabetic patients with uncontrolled glycemia.

Preliminary application of CT on accessing aortic arch calcification during parathyroid SPECT/CT in patients with renal secondary hyperparathyroidism / 中华核医学与分子影像杂志

Objective:To access the clinical value and related risk factors of aortic arch calcification (AoAC) in patients with renal secondary hyperparathyroidism (SHPT) on CT during parathyroid SPECT/CT imaging.Methods:From January 2014 to May 2021, 136 renal SHPT patients (70 males, 66 females, age (50.1±11.4) years) who underwent parathyroid 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT/CT in Affiliated Jiangyin Hospital of Nantong University were retrospectively enrolled. AoAC score was estimated with CT(1-5), and patients were divided into none-light AoAC group (AoAC score<3) and moderate-severe AoAC group (AoAC score≥3). Independent-sample t test or Mann-Whitney U test was used to compare differences of various indicators between two groups. Univariate binary logistic regression was used to analyze the influencing factors of AoAC. Results:Of 136 renal SHPT patients, 111(81.62%) were AoAC detected by CT. There were 84 patients in none-light AoAC group and 52 patients in moderate-severe AoAC group. The age ((46.7±9.8) vs (55.7±11.6) years; t=-4.84, P<0.001), pulse pressure (52(41, 64) vs 60(51, 70) mmHg (1 mmHg=0.133 kPa); z=-3.27, P=0.001), serum corrected calcium (2.41(2.28, 2.53) vs (2.49±0.22) mmol/L; z=-2.50, P=0.013), serum phosphorus ((1.95±0.39) vs (2.14±0.48) mmol/L; t=-2.54, P=0.012), calcium phosphorus product ((4.68±1.07) vs (5.29±1.10) mmol 2/L 2;t=-3.21, P=0.013) and parathyroid hormone (PTH) level (106.30(90.15, 127.45) vs 109.90(87.93, 157.63) pmol/L; z=-2.09, P=0.036) between non-light AoAC group and moderate-severe AoAC group were significantly different. Logistic regression analysis showed that serum phosphorus (odds ratio ( OR)=7.261, 95% CI: 2.416-21.819, P<0.001), calcium and phosphorus product ( OR=1.598, 95% CI: 1.073-2.380, P=0.021) and PTH level ( OR=1.018, 95% CI: 1.007-1.029, P=0.001) were independent risk factors of AoAC. Conclusions:Hybrid SPECT/CT can be used for an effective method of evaluating AoAC in patients with renal SHPT. High serum phosphorus, high calcium phosphorus product and high PTH level may be independent risk factors of AoAC.

Research progress in pharmacokinetics/pharmacodynamics and therapeutic drug monitoring of biapenem / 中国药房

Biapenem is a carbapenem antibiotic， and can be used for the treatment of sepsis， pneumonia， lung abscess， chronic respiratory lesions secondary infection， complex urinary tract infection and pyelonephritis， etc. This article reviewed the studies on the pharmacokinetics， pharmacodynamics and therapeutic drug monitoring （TDM） of biapenem. The pharmacokinetic parameters of biapenem are not significantly different in healthy subjects， and there is no accumulation after multiple doses of biapenem. However， there are large differences in pharmacokinetic parameters in patients with severe disease and patients with abnormal renal function compared with healthy subjects， which leads to conventional treatment regimens not achieving the desired outcome. In terms of pharmacodynamics， biapenem can improve the rate of reaching the target value by increasing the frequency of administration and prolonging the infusion time. For patients with anuria in end-stage renal disease， dosing intervals can be extended to avoid drug accumulation. However, for patients with severe infection, a daily dose of 1.2 g still can not control infections caused by Acinetobacter baumannii or Pseudomonas aeruginosa, which limits its use in patients with severe disease. It is recommended to implement TDM in severe patients and patients with abnormal renal function， and explore the best dosing regimen for biapenem in combination with pharmacokinetic models to ensure that the time that the free blood concentration of biapenem remains above minimum inhibitory concentration as a percentage of the time between doses （%fT＞MIC） is within the effective range，so that biapenem can exert a greater efficacy in severe patients and patients with abnormal renal function. For medical institutions that cannot carry out TDM， the efficacy of biapenem can be maximized by increasing the frequency of administration and prolonging the infusion time. For infections caused by P. aeruginosa， A. baumannii and Serratia marcescens with high drug resistance rates， it is recommended to combine or replace other antibiotics.

Analysis of natural regression and influencing factors of HSIL in the cervix of childbearing age patients / 中华妇产科杂志

Objective: To investigate the natural regression and related factors of high-grade squamous intraepithelial lesion (HSIL) in the cervix of childbearing age women, and to evaluate the applicability of conservative management for future fertility needs. Methods: This study included 275 patients of reproductive age with fertility needs, who were diagnosed as HSIL by biopsy from April 30, 2015 to April 30, 2022, including 229 cases (83.3%) cervical intraepithelial neoplasia (CIN) Ⅱ and 46 cases (16.7%) CIN Ⅱ-Ⅲ. They were followed-up without immediate surgery in the First Affiliated Hospital of Nanjing Medical University. The median follow-up time was 12 months (range: 3-66 months). The regression, persistence and progression of lesions in patients with HSIL were analyzed during the follow-up period, the influencing factors related to regression and the time of regression were analyzed. Results: (1) Of the 275 HSIL patients, 213 cases (77.5%, 213/275) experienced regression of the lesion during the follow-up period. In 229 CIN Ⅱ patients, 180 cases (78.6%) regressed, 21 cases (9.2%) persisted, and 28 cases (12.2%) progressed. In 46 CIN Ⅱ-Ⅲ patients, 33 cases (71.7%) regressed, 12 cases (26.1%) persisted, and 1 case (2.2%) progressed to invasive squamous cell carcinoma stage Ⅰ a1. There was no significant difference in the regression rate between the two groups (χ2=1.03, P=0.309). (2) The average age at diagnosis, age <25 years old at diagnosis were independent influencing factor of HSIL regression in univariate analysis (all P<0.05). There was no significant difference between HSIL regression and pathological grading, the severity of screening results, human papillomavirus (HPV) genotype, colposcopy image characteristics, number of biopsies during follow-up and pregnancy experience (all P>0.05). (3) The median regression times for patients aged ≥25 years and <25 years at diagnosis were 15 and 12 months, respectively. Kaplan-Meier analysis showed that age ≥25 years at diagnosis significantly increased the median regression time compared to <25 years (χ2=6.02, P=0.014). Conclusions: For HSIL patients of childbearing age, conservative management without immediate surgical intervention is preferred if CINⅡ is fully evaluated through colposcopy examination. Age ≥25 years at diagnosis is a risk factor affecting the prognosis of HSIL patients.

Analysis and prediction of thyroid cancer morbidity and mortality trends in China / 中华流行病学杂志

Objective: To analyze the morbidity and mortality trends of thyroid cancer in China from 1990 to 2019, explore the causes of the trends, and predict morbidity and mortality in the future. Methods: The morbidity and mortality data of thyroid cancer in China from 1990 to 2019 were collected from the 2019 Global Burden of Disease database. The Joinpoint regression model was used to describe the change trends. Based on the morbidity and mortality data from 2012 to 2019, a grey model GM (1,1) was constructed to predict the trends in the next ten years. The model was tested by the posterior error method and residual test method. Results: In all populations, men and women, the AAPC values of the crude morbidity rates were 4.15% (95%CI: 3.86%-4.44%, P<0.001), 5.98% (95%CI: 5.65%-6.31%, P<0.001) and 3.23% (95%CI: 2.94%-3.53%, P<0.001) respectively, the AAPC values of age-standardized morbidity rates were 2.47% (95%CI: 2.12%-2.83%, P<0.001), 3.98% (95%CI: 3.68%-4.29%, P<0.001), 1.65% (95%CI: 1.38%-1.93%, P<0.001), the AAPC values of crude mortality rates were 2.09% (95%CI: 1.92%-2.25%, P<0.001), 3.68% (95%CI: 3.45%-3.90%, P<0.001), 0.60% (95%CI: 0.50%-0.71%, P<0.001). The age-standardized mortality rates in men showed a fluctuating trend of first decrease (1990-1994), then increase (1994-2012), and then decrease (2012-2019) (AAPC=1.35%, 95%CI: 1.16%-1.53%, P<0.001). The age-standardized mortality rate in women continuously decreased (AAPC=-1.70%, 95%CI: -1.82%- -1.58%, P<0.001). The GM (1,1) models can be used for medium and long-term predictions. The results of the residual test show that the average relative error values of all models are less than 10.00%, the prediction accuracy values are more than 80.00%, and the prediction effects are good. The results of the posterior error method show that all the prediction results are good except the qualified prediction of the age-standardized morbidity rate in men. In 2029, the crude morbidity rates would increase to 3.57/100 000, 2.78/100 000, and 4.40/100 000, respectively, and the age-standardized incidence rates would increase to 2.38/100 000, 1.89/100 000, and 2.88/100 000, respectively, the crude mortality rates would increase to 0.57/100 000, 0.62/100 000 and 0.53/100 000, and the age-standardized mortality rates would decrease to 0.33/100 000, 0.42/100 000 and 0.27/100 000 in all population, men and women in China. Conclusions: The overall, gender- specific age-standardized mortality rates showed downward trends in the last decade or so, and the prediction results showed that it might further decline. However, the crude morbidity rates, age-standardized and crude mortality rates have been on the rise, and the population aging is becoming increasingly serious in China, which requires close attention and targeted prevention and control measures.

Relationship between smoking and the risk of morbidity of chronic obstructive pulmonary diseases among residents aged 30 years and above in Sichuan Province: a prospective study / 中华流行病学杂志

Objective: To investigate the morbidity of chronic obstructive pulmonary diseases (COPD) in residents aged 30 years and above in Sichuan Province, and analyze the effect of smoking on the risk of morbidity on COPD. Methods: From 2004 to 2008, people were randomly selected from Pengzhou, Sichuan Province. All the local people aged 30-79 years were asked to receive questionnaire survey, physical examination and pulmonary function testing, and long-term follow-up to determine the morbidity of COPD. Cox proportional hazard regression model was used to analyze the relationship between smoking and COPD. Results: In 46 540 participants, the current smoking rates were 67.31% in males and 8.67% in females, there were 3 101 new cases of COPD, with a cumulative incidence of 6.66%. Adjusted for age, gender, occupation, marriage, income level, educational level, BMI, daily total physical activity, current cooking frequency, whether there was smoke exhaust device at present and frequency of passive smoking exposure, multivariate Cox proportional hazard regression analysis showed that compared with the non-smoking population, current smoking and quitting smoking increased the risk of COPD, with HR of 1.42 (95%CI:1.29-1.57) and 1.34 (95%CI:1.16-1.53). Compared with people who never or occasionally smoke, the risk of morbidity on COPD increased with the increase of average daily smoking volume, mixed smoking at present, mixed smoking at the beginning increased the risk of COPD, with HR of 1.79 (95%CI: 1.42-2.25) and 2.12 (95%CI: 1.53-2.92), started smoking at the age of <18 years old and ≥18 years old increased the risk of COPD, with HR of 1.61 (95%CI:1.43-1.82) and 1.34 (95%CI: 1.22-1.48), inhaling into the mouth, throat and lung during smoking increased the risk of COPD, with HR of 1.30 (95%CI: 1.16-1.45), 1.63 (95%CI: 1.45-1.83) and 1.37 (95%CI: 1.21-1.55). Adjusted for multiple confounding factors and adjusted for regression dilution bias, the average daily smoking volume, the age of starting smoking and the depth of smoking inhalation had an impact on the incidence of COPD, and the gender difference was particularly prominent. Conclusions: Smoking increased the risk of morbidity on COPD, which was related to the average daily smoking volume, the type of smoking, the age of starting smoking and the depth of smoking inhalation. Tobacco control should comprehensively consider the specific characteristics of smoking, so as to prevent COPD.

Review of traditional Chinese medicines in ameliorating neuropsychiatric diseases by improving the levels of monoamine neurotransmitters via gut microbiota regulation / 中国中药杂志

The degeneration of monoaminergic system and the reduction of monoamine neurotransmitters(MNTs) are associated with the occurrence of a variety of neuropsychiatric diseases, becoming the key indicators for clinical diagnosis and treatment. Recent studies suggested gut microbiota could influence the occurrence, development, and treatment of neuropsychiatric diseases by directly or indirectly regulating the synthesis and metabolism of MNTs. Rich clinical experience has been accumulated in the amelioration and treatment of neuropsychiatric diseases by traditional Chinese medicines. The traditional oral administration method demonstrates obvious advantages in regulating gut microbiota. It provides a new idea for explaining the pharmacodynamic material basis and mechanism of traditional Chinese medicines in ameliorating neuropsychiatric disease by improving the levels of MNTs via gut microbiota regulation. Focusing on three common neuropsychiatric diseases including Alzheimer's disease, Parkinson's disease, and major depression, we summarized the pathways of gut microbiota in regulating the levels of MNTs and the paradigms of traditional Chinese medicines in ameliorating neuropsychiatric diseases via the "bacteria-gut-brain axis", aiming to provide ideas for the development of drugs and treatment schemes.

Relaxin-3 Ameliorates Diabetic Cardiomyopathy by Inhibiting Endoplasmic Reticulum Stress.

Background: This study is aimed at investigating whether relaxin-3 exhibits protective effects against cardiomyopathy in diabetic rats by suppressing ERS. Methods: Eighty male SD rats were randomly divided into two groups: controls (n = 20) and diabetes (n = 60). The streptozotocin-treated rats were randomly divided into three groups: diabetic group (DM), low-dose relaxin-3 group (0.2 µg/kg/d), and high-dose relaxin-3 group (2 µg/kg/d). The myocardial tissues and collagen fiber were observed by hematoxylin and eosin (H&E) and Masson staining. Serum brain natriuretic peptide (BNP), troponin (TNI), myoglobin, interleukin (IL-17), interleukin (IL)-1α, and tumor necrosis factor (TNF)-α were determined by ELISA. The protein expression of glucose regulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the heart tissue of each group was detected by Western blot analysis. Results: (1) HE and Masson staining indicated that relaxin-3 could attenuate myocardial lesions and myocardial collagen volume fraction. (2) BNP, TnI, and myoglobin in the DM group at four and eight weeks were significantly higher than in the controls (P < 0.01). The relaxin-3-treated groups showed significantly reduced serum BNP, TnI, and myoglobin levels compared with the DM group (P < 0.05). (3) IL-17, IL-1α, and TNF-α levels in the DM rats at 4 weeks were higher than in the controls (P < 0.05). Low or high dose of relaxin-3-treated groups showed reduced serum IL-17 and TNF-α levels compared with the DM group at four and eight weeks (P < 0.05). (4) CHOP and GRP78 protein expression was increased in the DM group at four and eight weeks compared with the controls (P < 0.01), and small and large doses of relaxin-3 significantly reduced GRP78 and CHOP protein expression. Conclusions: Exogenous relaxin-3 ameliorates diabetic cardiomyopathy by inhibiting ERS in diabetic rats.

[Retention Effect of Heavy Metals in Rivers of a Typical Mountainous City by Cascade Weirs: A Case Study of Liangtan River in Chongqing].

Contaminants such as heavy metals in rivers are partially retained in the sediments at the bottom as a result of the altered water regime within the cascade weirs. The associated heavy metals in the sediments can affect surface water quality and ecology for a long period. In May 2020, sediments were collected in a typical mountainous river (Liangtan River) with cascade weirs in the main urban area of Chongqing. The accumulation of sediments in each river section, the content of heavy metals, and other basic physicochemical indicators in the samples were monitored. The results showed that the average ω(As), ω(Cd), ω(Cu), ω(Hg), ω(Ni), and ω(Pb) in the sediments of the main stream of Liangtan River were (4.66±4.78), (0.361±0.256), (32.30±14.38), (0.069±0.039), (33.47±15.37), and (26.34±11.52) mg·kg-1, respectively. A large coefficient of spatial variation regarding the content of heavy metals in the sediments across the sampling sites was observed owing to the uneven spatial distribution of pollution sources and the destruction of river connectivity by cascade weirs. The modified geoaccumulation index (Im) showed that Cd was the most polluted heavy metal element in the sediments. Of the monitored river sections, 12.50% approached or were at moderate pollution levels, and these sections were mainly found in the upstream and downstream reaches of Liangtan River with relatively concentrated construction lands. The potential ecological risk assessment index method (RI) and the sediment quality guideline method (SQGs) showed that, in addition to Cd and Hg with a high pollution level and strong toxicity, Ni in the sediments also posed a potential threat to the ecological safety of surface water due to its high background content in the watershed. The total amounts of As, Cd, Cu, Hg, Ni, and Pb retained in the sediments by cascade weirs were estimated to be 446.10, 47.28, 4997.80, 10.81, 5135.68, and 4048.16 kg, respectively, in which Cd, Ni, and Pb were identified to be the major threats to the ecological safety of surface water over a long period. The upper reaches prior to the weirs with the most retained heavy metals and the easier formation of an anaerobic environment are suggested to be the key areas for investigation of the endogenous release of heavy metals. Source apportionment of heavy metals in river sediments through the combination of principal component analysis and cluster analysis revealed that Cd, Cu, and Pb mainly originated from residential/industrial point source pollution. Hg mainly originated from agricultural non-point source pollution, whereas As and Ni mainly originated from natural soil erosion.

Case Report: A Rare Case of Acute Anterior Myocardial Infarction Simultaneously Associated With Aortic Mural Thrombosis Due to Essential Thrombocytosis.

Background: Essential thrombocytosis (ET) simultaneously complicated with acute myocardial infarction and aortic thrombosis is extremely rare and associated with poor outcomes. Case: A 54-year-old female was admitted to our emergency department with abdominal pain for 3 h. ST-segment elevation in leads V1-V3 on electrocardiography led to the diagnosis of acute anterior myocardial infarction. Coronary angiography demonstrated total occlusion of the proximal left anterior descending artery, and the patient was treated with angioplasty and placement of a drug-eluting stent. CT angiography revealed a massive mural thrombus located in the descending aorta. Bone marrow biopsy confirmed the diagnosis of ET. The patient was successfully treated with antithrombotic therapy and hydroxyurea. Conclusion: At present, the clinical diagnosis and treatment of ET complicated with acute myocardial infarction and aortic thrombosis are mostly based on literature reports. Early target vessel revascularization, antiplatelet and anticoagulant combined with cytoreductive therapy may improve the prognosis. Clinicians should consider the risk of bleeding and thrombosis and create individualized treatment strategies for these patients.

A novel tumor-specific broad-spectral monoclonal antibody to PL2L60 is highly effective for the treatment of various types of cancers from human and mouse.

There are numerous antibodies used for cancer therapy in clinic, but they are essentially less efficacy than expected. None of them has tumor-specific and broad-spectral properties. PIWIL2-like (PL2L) protein 60 (PL2L60) is a product of alienated activation of PIWIL2 gene, and has been found to be specifically and widely expressed in various types of cancers, including hematopoietic and solid ones. Current study aims to investigate whether a monoclonal antibody (mAb) to PL2L60 has both tumor-specific and broad-spectral properties, which can be used universally to treat various types of cancers. The expression of PL2L60 protein in the cell surface and cytoplasm were determined in a panel of human and mouse tumor cell lines by flow cytometry, immunofluorescent microscopy and Western Blotting. The apoptosis and the cell cycle arrest of the tumor cells treated with mAb KAO3 were evaluated by flow cytometry. The tumorigenesis of the mAb KAO3-pretreated tumor cells was determined by tumor incidence and tumor size, and the efficacy of mAb KAO3 treatment on tumor growth in tumors-bearing mice were kinetically evaluated. Complement-dependent cytotoxicity (CDC) assay was used to determine the capacity of mAb KAO3 to kill tumor cells. Treatment of human or mouse tumor cells from hematopoietic or solid tumors with mAb KAO3 at the time of inoculation efficiently inhibited tumorigenesis in the severe combined immunodeficient (SCID) mice. Moreover, injection of mAb KAO3 into established tumors significantly inhibited their growth, and prolonged survival of the tumor-bearing mice, including lymphoma, breast cancer, lung cancer and cervical cancer. The efficacy of mAb KAO3 treatment is likely associated with its binding to PL2L60 expressed on tumor cell surface, which may lead to cancer cell death through blocking cell cycling and/or activation of complement. In conclusion, we have identified a tumor-specific mAb to PL2L60 (KAO3), which may be used potentially to treat all the types of human cancers including from both hematopoietic and solid ones.

T cell response to intact SARS-CoV-2 includes coronavirus cross-reactive and variant-specific components

SARS-CoV-2 provokes a brisk T cell response. Peptide-based studies exclude antigen processing and presentation biology and may influence T cell detection studies. To focus on responses to whole virus and complex antigens, we used intact SARS-CoV-2 and full-length proteins with DC to activate CD8 and CD4 T cells from convalescent persons. T cell receptor (TCR) sequencing showed partial repertoire preservation after expansion. Resultant CD8 T cells recognize SARS-CoV-2-infected respiratory cells, and CD4 T cells detect inactivated whole viral antigen. Specificity scans with proteome-covering protein/peptide arrays show that CD8 T cells are oligospecific per subject and that CD4 T cell breadth is higher. Some CD4 T cell lines enriched using SARS-CoV-2 cross-recognize whole seasonal coronavirus (sCoV) antigens, with protein, peptide, and HLA restriction validation. Conversely, recognition of some epitopes is eliminated for SARS-CoV-2 variants, including spike (S) epitopes in the alpha, beta, gamma, and delta variant lineages.

Clinical study of Huzhang Polou Decoction combined with acupoint application for the children with mycoplasma pneumonia complicated with atelectasis and phlegm-heat obstruction / 国际中医中药杂志

Objective:To evaluate the clinical efficacy of Huzhang Polou Decoction combined with acupoint application in the treatment of children with mycoplasma pneumoniae pneumonia (MPP) complicated with atelectasis.Methods:A total of 105 MPP children with atelectasis and phlegm-heat obstructing lung syndrome in our hospital from August 2019 to March 2022, who met the inclusion criteria, were divided into control group (53 cases) and observation group (52 cases), by random number table method. The control group was given azithromycin sequential therapy on the basis of conventional western medicine treatment, and the observation group was given Huzhang Polou Decoction and acupoint application on the basis of the control group. Both groups were treated for 19 days. TCM syndromes were scored before and after treatment. The FEV1 and peak expiratory flow rate (PEF) were measured by pulmonary function measurement instrument. The CRP was measured by immunoturbidimetry and procalcitonin (PCT) was measured by ELISA. The recovery time of fever, disappearance time of cough and sputum, disappearance time of lung rales, lung recruitment time, and adverse reactions during treatment were recorded, and the clinical efficacy was evaluated.Results:The total effective rate was 96.15% (50/52) in the observation group and 84.91% (45/53) in the control group, and the difference between the two groups was statistically significant ( χ2=3.85, P=0.050). After treatment, the TCM syndrome score of the observation group was significantly lower than that of the control group ( t=22.78, P<0.01). FEV1 [(1.87±0.29) L vs. (1.54±0.28) L, t=5.93] and PEF [(79.82±6.29) L/min vs. (74.32±6.30) L/min, t=4.48] were significantly higher than those in the control group ( P<0.01). The levels of serum CRP [(9.18±2.98) mg/L vs. (12.34±3.00) mg/L, t=5.42] and PCT [(0.60±0.15) ng/L vs. (0.96±0.21) ng/L, t=9.93] were significantly lower than those in the control group ( P<0.01). The recovery time of fever, disappearance time of cough and sputum, disappearance time of lung rale and lung recruitment time in the observation group were significantly earlier than those in the control group ( t=7.27, 6.84, 3.76, 5.87, all Ps<0.01). During treatment, the incidence of adverse reactions was 3.77% (2/53) in the control group and 1.92% (1/52) in the observation group, and there was no significant difference between the two groups ( χ2=0.32, P=0.569). Conclusion:The Huzhang Polou Decoction combined with acupoint application can improve the pulmonary function of children with MPP complicated with atelectasis, reduce the level of serum inflammatory cytokines, improve the clinical efficacy safely.