Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective:To assess the value of cerebral small vessel disease (CSVD) burden in predicting prognosis in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (LVO) after endovascular therapy (EVT).Methods:The study was a cross-sectional study. A total of 242 patients with AIS due to anterior circulation LVO received EVT in the First Affiliated Hospital of Nanjing Medical University from February 2018 to September 2022. The clinical and imaging data of all patients were analyzed retrospectively. On follow-up MRI within 7 days after EVT, CSVD features [white matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed, cerebral atrophy] and CSVD burden score (0-5) was evaluated. Modified Rankin scale (mRS) score at 90 days after EVT was assessed. Patients were categorized into a mild burden group (0-1 points) and a moderate-severe burden group (2-5 points) based on CSVD burden score. Meanwhile, patients were categorized into a good prognosis group (0-2 points) and a bad prognosis group (3-6 points) based on mRS score at 90 days after EVT. Mann-Whitney U test and χ2 test were used to compare the difference of clinical and imaging indexes between the 2 groups, and variables with P<0.1 in the univariate analysis were included in the multifactorial logistic regression to screen for independent factors to predict the prognosis. Results:There were 169 patients in the good prognosis group and 73 patients in the bad prognosis group out of 242 patients. Compared with the good prognosis group, age, incidence of hyperlipidemia, baseline National Institutes of Health Stroke Scale (NIHSS) scores, incidence of hemorrhagic conversion, CSVD burden scores, incidence of periventricular WMH scores of 3 and/or deep WMH scores≥2, and incidence of moderate-severe cerebral atrophy of patients in the bad prognosis group were higher, and the incidence of complete recanalization was lower (all P<0.05). Multivariate analysis showed hyperlipemia ( OR=8.438, 95% CI 1.691-42.119, P=0.009), baseline NIHSS score ( OR=1.103, 95% CI 1.047-1.162, P<0.001), complete recanalization ( OR=0.131, 95% CI 0.038-0.454, P=0.001) and hemorrhage transformation ( OR=1.952, 95% CI 1.031-3.697, P=0.040) were independent factors for the prognosis of EVT in patients with LVO AIS. There were 157 cases in the mild burden group and 85 cases in the moderate-severe burden group. The 90-day mRS score was higher in the moderate-severe burden group compared with the mild burden group ( Z=-2.24, P=0.025). Conclusion:CSVD burden has some clinical implications in predicting the prognosis of EVT in patients with anterior circulation LVO AIS.

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

Illustrated Classic of Materia Medica （Ben Cao Tu Jing）， compiled in 1061， is regarded as the crystallization of the second national survey of Chinese medicinal resources in the history of China after the Newly Revised Materia Medica （Xin Xiu Ben Cao）， which serves as a precious source for exploring the Chinese medicinal resources in the Song Dynasty. The Illustrated Classic of Materia Medica （Ben Cao Tu Jing） covers 50 illustrations for Chinese medicinal materials named after geographical names of Jiangsu Province， 39 of which have been verified in today's Jiangsu Province. To be specific， Chinese medicinal materials in 32 illustrations can be traced back to their species， those in four illustrations to genera， and those in three illustrations to family. The remaining 12 illustrations remain to be further verified. The origins of most Chinese medicinal materials in the illustrations can be traced， which is attributed to their exquisiteness and lifelikeness as well as the detailed descriptions of the characters of the original plants and animals. In the textual research of these illustrations， we have noticed that there are inconsistencies between pictures and texts， and different illustrations may be derived from the same origin. This is believed to be related to SU Song's principle of collation that "for all Chinese medicinal materials presented as examples， if their shapes and categories recorded are not consistent with those in the literature， they will be retained. If there is any connection with the literature， they will be annotated according to literature to make their origins clear". As revealed by the distribution of Chinese medical materials in Jiangsu Province reported in the Illustrated Classic of Materia Medica （Ben Cao Tu Jing）， the utilization and development of Jiangsu medicinal materials during the Northern Song Dynasty were mainly concentrated in the low-altitude valleys and coastal areas. It could be seen from the illustrations of Chinese medicinal materials named after geographical names of today's Jiangsu Province that the production areas with a large number of illustrations were relatively developed in politics， economy， and transportation at that time， which enabled the medicinal resources to be fully utilized.

Child, Preschool ; Humans ; Lymphohistiocytosis, Hemophagocytic ; diagnosis ; genetics ; therapy ; Male

OBJECTIVETo investigate the meaning of pedicle exposure technique for screw fixation on atlas with the vertebral groove height less than 4 mm by using reconstructive computed tomography.

METHODSFrom April 2015 to June 2015, 84 pedicles of 51 patients with groove heights less than 4 mm were studied by digital reconstruction respectively. Parameters of atlas pedicle screw fixation were measured.

RESULTSAmong the 51 cases, the vertebral groove height was (3.28±0.51) mm. Lateral mass heights, lateral mass widths and the transition area heights between lateral mass and posterior arch were fit for 3.5 mm screw implanting. Ideal pedicle screw trajectory lengths from 0° to 15° (0°, 5°, 10°, 15°) were (27.36±1.81), (27.01±1.68), (27.07±1.75), (27.48±1.72) mm, exposed trajectory lengths from 0° to 15°(0°, 5°, 10°, 15°) were(23.44±1.79), (23.87±1.84), (24.58±1.89), (25.56±2.01) mm, trajectory length of lateral mass was (20.78±2.05) mm. The mean CT values on 5 sections through pedicle trajectory and lateral mass trajectory were (701.89±141.48) HU and (599.11±137.33) HU, respectively. There were no significant differences between ideal pedicle trajectory lengths from 0° to 15°(>0.05). Exposed trajectory lengths was significantly increased accompanying with medial angles increasing (<0.05), and was longer than trajectory lengths of lateral mass (<0.05). CT value of pedicle screws was higher than CT value of lateral mass screws significantly (<0.01).

CONCLUSIONSScrews can be implanted in atlas with vertebral groove height less than 4 mm by using pedicle exposure technique. Few trajectory lengths will be sacrificed with favorable pull out strength due to adequate bone mass purchased.

BACKGROUNDContinuous negative pressure drainage (CNPD) is widely used after lower lumbar internal fixation; however, it may cause tremendous blood loss and lead to postoperative hemorrhagic anemia. The present study explored the efficacy and safety of improved intermittent-clamped drainage (ICD) for lower lumbar internal fixation.

METHODSThis was a prospective study that included 156 patients with decompression of the spinal canal and internal fixation for the first time from January 2012 to December 2014. The patients were randomly divided into ICD group and CNPD group, and each group had 78 cases. A drainage tube was placed under the deep fascia in all patients within 10 min after the commencement of wound closure. The postoperative drainage amount at different time points, the hemoglobin level, and postoperative complications were recorded and compared between the two groups. Shapiro-Wilk test, independent samples t-test, and Mann-Whitney U-test were used in this study.

RESULTSThe drainage amount was significantly reduced in the ICD group, as compared with the CNPD group (Z = 10.74, P < 0.01). The mean total drainage amount (in ml) of the single-segment and two-segment procedures was significantly greater in the CNPD group than the ICD group (Z = 10.63 and 10.75, respectively; P < 0.01). For the adverse events, there was no significant difference in postoperative temperature, wound problem, and complications between the two groups.

CONCLUSIONSThe present study showed a statistically significant reduction in postoperative drainage amount between ICD and CNPD groups, and ICD is an effective, convenient, and safe method for routine use in lower lumbar surgery. It is essential to focus on the effect of clamping drainage with long-segment surgical procedure and complex lumbar disease in the further investigation, as well as the effect of clamping on long-term functional outcomes.

Blood Loss, Surgical ; prevention & control ; Drainage ; methods ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Intervertebral Disc Degeneration ; surgery ; Lumbar Vertebrae ; surgery ; Male ; Middle Aged ; Prospective Studies ; Spinal Fusion ; methods ; Treatment Outcome

The feasibility of simultaneously loading both liposoluble and water-soluble components of Salvia miltiorrhiza in emulsion was discussed, in order to provide new ideas in comprehensive application of effective components in S. miltiorrhiza in terms of technology of pharmaceutics. With tanshinone II (A) and salvianolic acid B as raw materials, soybean phospholipid and poloxamer 188 as emulsifiers, and glycerin as isoosmotic regulator, the central composite design-response surface method was employed to optimize the prescription. The coarse emulsion was prepared with the high-speed shearing method and then homogenized in the high pressure homogenizer. The biphasic drug-loading intravenous emulsion was prepared to investigate its pharmaceutical properties and stability. The prepared emulsion is orange-yellow, with the average diameter of 241 nm and Zeta potential of -35.3 mV. Specifically, the drug loading capacity of tanshinone II (A) and salvianolic acid B were 0.5 g x L(-1) and 1 g x L(-1), respectively, with a good stability among long-term retention samples. According to the results, the prepared emulsion could load liposoluble tanshinone II (A) and water-soluble salvianolic acid B simultaneously, which lays a pharmaceutical foundation for giving full play to the efficacy of S. miltiorrhiza.
Chemistry, Pharmaceutical ; instrumentation ; methods ; Drugs, Chinese Herbal ; chemistry ; Emulsions ; chemistry ; Quality Control ; Salvia miltiorrhiza ; chemistry

OBJECTIVETo study the prognostic significance of CD47 in a NOD/SCID mouse model of acute myeloid leukemia (AML) and the best strategy for targeted therapy for this disease.

METHODSCD34(+)CD38(-) leukemia stem cells (LSCs) were separated and transplanted into NOD/SCID mice to establish a mouse model of acute monocytic leukemia (AMoL). Anti-human CD47 antibody, alone or combined with cytosine arabinoside (Ara-C), was used to treat the mice with AMoL for 7-14 days, and therapeutic efficacy was assessed. LSCs were cultured together with mouse macrophages in culture medium containing anti-CD47 or anti-CD45 monoclonal antibody for 2 hours, to observe the phagocytic ability of macrophages to LSCs.

RESULTSCD34(+)CD38(-) LSCs existed among THP-1 cells, with a content of about (0.12 ± 0.06)%, and a mouse model of AML was successfully established after the purified CD34(+)CD38(-) LSCs (97.0% ± 1.7%) were transplanted into NOD/SCID mice. The in vivo experiment showed that mice with AMoL had the most significant decrease in CD33(+)CD45(+) leukemia cells in peripheral blood and bone marrow and survived the longest after being treated with Ara-C (7 days) plus anti-CD47 monoclonal antibody (14 days) (P < 0.01). After 2 hours of in vitro culture, the phagocytic index in the culture medium containing anti-CD47 monoclonal antibody was significantly higher than in the culture medium containing anti-CD45 monoclonal antibody (76.9% ± 12.2% vs 7.60% ± 2.4%; P < 0.05).

CONCLUSIONSHigh expression of CD47 is an adverse prognostic factor in AML. Combination therapy with anti-CD47 monoclonal antibody and Ara-C can effectively eliminate leukemia cells and LSCs, demonstrating great clinical significance in curing AML.

Animals ; Antibodies, Monoclonal ; administration & dosage ; CD47 Antigen ; immunology ; physiology ; Cytarabine ; administration & dosage ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; mortality ; pathology ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Prognosis