ObjectiveTo prepare triptolide-Chuanxiong Rhizoma extract ethanol transfersomes（TP-CX@TESs）， conduct its quality evaluation， and investigate its in vitro anti-inflammatory efficacy and the underlying mechanisms. MethodsTP-CX@TESs was prepared via the ultrasonic injection method. With encapsulation efficiency and particle size as evaluation indicators， Box-Behnken design-response surface methodology（BBD-RSM） was employed to optimize the formulation process. The TP-CX@TESs prepared under the optimal process was characterized and evaluated for in vitro transdermal performance. A lipopolysaccharide（LPS）-induced RAW264.7 cell inflammation model was established. After 24 h of drug intervention， the levels of inflammatory factors such as nitric oxide（NO）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α） in the cell supernatant were detected. Western blot was used to determine the protein expression levels of Janus kinase 2（JAK2）， signal transducer and activator of transcription 3（STAT3）， and α7 nicotinic acetylcholine receptor（α7nAChR）， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was applied to measure the mRNA expression levels of JAK2， STAT3， the encoding gene of α7nAChR（CHRNA7）， and nuclear transcription factor-κB（NF-κB）. ResultsResults of BBD-RSM showed that the optimal formulation for preparing TP-CX@TESs was as follows：egg yolk lecithin content of 2.3%， ethanol volume fraction of 30%， and ratio of polysorbate-80 to egg yolk lecithin of 2∶5. Microscopic characterization revealed that TP-CX@TESs exhibited a spherical-like structure with a particle size of （105.60±3.85） nm， a polydispersity index of 0.19±0.03， and a Zeta potential of （-15.89±0.98） mV. The encapsulation efficiencies of triptolide， ferulic acid， and ligustilide were （76.88±4.40）%， （78.84±4.40）%， and （65.88±0.06）%， respectively. Both in vitro release and transdermal penetration of triptolide， ferulic acid， and ligustilide in TP-CX@TESs all followed the first-order kinetic model， showing a certain sustained-release property. Experimental results in RAW264.7 cells indicated that TP-CX@TESs significantly inhibited the release of NO， TNF-α， and IL-6（P<0.01）， remarkably upregulated the protein expression levels of STAT3 and α7nAChR（P<0.01）， increased the mRNA expression level of CHRNA7， and significantly downregulated the mRNA expression level of NF-κB（P<0.05， P<0.01）. ConclusionThe optimized formulation process of TP-CX@TESs is simple and feasible， along with favorable in vitro release property， good transdermal permeability， and excellent in vitro anti-inflammatory activity， the mechanism is related to the inhibition of NF-κB.

ObjectiveTo prepare triptolide-Chuanxiong Rhizoma extract ethanol transfersomes（TP-CX@TESs）， conduct its quality evaluation， and investigate its in vitro anti-inflammatory efficacy and the underlying mechanisms. MethodsTP-CX@TESs was prepared via the ultrasonic injection method. With encapsulation efficiency and particle size as evaluation indicators， Box-Behnken design-response surface methodology（BBD-RSM） was employed to optimize the formulation process. The TP-CX@TESs prepared under the optimal process was characterized and evaluated for in vitro transdermal performance. A lipopolysaccharide（LPS）-induced RAW264.7 cell inflammation model was established. After 24 h of drug intervention， the levels of inflammatory factors such as nitric oxide（NO）， interleukin-6（IL-6）， and tumor necrosis factor-α（TNF-α） in the cell supernatant were detected. Western blot was used to determine the protein expression levels of Janus kinase 2（JAK2）， signal transducer and activator of transcription 3（STAT3）， and α7 nicotinic acetylcholine receptor（α7nAChR）， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was applied to measure the mRNA expression levels of JAK2， STAT3， the encoding gene of α7nAChR（CHRNA7）， and nuclear transcription factor-κB（NF-κB）. ResultsResults of BBD-RSM showed that the optimal formulation for preparing TP-CX@TESs was as follows：egg yolk lecithin content of 2.3%， ethanol volume fraction of 30%， and ratio of polysorbate-80 to egg yolk lecithin of 2∶5. Microscopic characterization revealed that TP-CX@TESs exhibited a spherical-like structure with a particle size of （105.60±3.85） nm， a polydispersity index of 0.19±0.03， and a Zeta potential of （-15.89±0.98） mV. The encapsulation efficiencies of triptolide， ferulic acid， and ligustilide were （76.88±4.40）%， （78.84±4.40）%， and （65.88±0.06）%， respectively. Both in vitro release and transdermal penetration of triptolide， ferulic acid， and ligustilide in TP-CX@TESs all followed the first-order kinetic model， showing a certain sustained-release property. Experimental results in RAW264.7 cells indicated that TP-CX@TESs significantly inhibited the release of NO， TNF-α， and IL-6（P<0.01）， remarkably upregulated the protein expression levels of STAT3 and α7nAChR（P<0.01）， increased the mRNA expression level of CHRNA7， and significantly downregulated the mRNA expression level of NF-κB（P<0.05， P<0.01）. ConclusionThe optimized formulation process of TP-CX@TESs is simple and feasible， along with favorable in vitro release property， good transdermal permeability， and excellent in vitro anti-inflammatory activity， the mechanism is related to the inhibition of NF-κB.

Acute urinary retention(AUR)occurs frequently among astronauts on orbit.The current treatment is complex and easy to damage the urethra,which seriously affects the life and work of astronauts.In contrast,acupuncture,a traditional Chinese remedy,has shown promising results in managing urinary retention.However,the specific acupoints that could potentially prevent AUR remain uncertain due to the unique physiological conditions experienced by individuals in space compared to those on Earth.To address this gap,our research delved into the mechanisms of AUR and acupuncture within both traditional Chinese medicine and modern medical practices.We conducted a thorough literature review from Pubmed,Web of Science,CNKI,Wanfang database,VIP database and Chinese Medical Code database.A hierarchical evidence-scoring approach was utilized to analyze the included literatures,thus devised acupuncture protocols for the treatment of AUR.The outcomes of our study aim to establish a foundation for the application of acupuncture in managing AUR.

Astronauts are affected by the space environment,and there are health problems in many systems of the body,which seriously affect the on-orbit work efficiency and the health recovery after landing.Although measures have been taken,there are still deficiencies.Acupuncture can regulate the body in a multi-target,multi-level and multi-system way to protect the health of astronauts,which is an effective measure to protect the health problems of astronauts.But there is no acupoint group database for aerospace medical problems,which limits the application of acupuncture in space.The aim of this paper is to solve the possible aerospace medical problems of astronauts by acupuncture.Firstly,the acupuncture indications in aerospace medicine are determined through literature research,expert consultation and expert consensus,and then the evidence collection,evidence evaluation and evidence aggregation are carried out through the"stratified evidence evaluation method"for ancient literature,modern literature and expert experience.Finally,acupoint prescriptions were recommended based on the comprehensive score of acupoints,and acupuncture prescriptions for all acupuncture indications in aerospace medicine were integrated to form an acupoint group database,so as to contribute more Chinese wisdom and solutions to solve aerospace medicine problems.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

Objective:To explore the protective effects of breastfeeding on behavioral problems at 4 years in children born to mothers with gestational diabetes mellitus (GDM).Methods:Based on the Ma' anshan Birth Cohort (MABC) study, 305 GDM women and their children were recruited in this study from Ma' anshan Maternal and Child Health Care Hospital from May 2013 to September 2014. Total breastfeeding duration was followed up at 42 d, 3, 6, 12, and 18 months postpartum as well as the breastfeeding intensity within 6 months. All the subjects were divided into breastfeeding group ( n=256, including exclusive breastfeeding and mixed feeding) or bottle feeding group ( n=49). Internalizing and externalizing behavioral problems at age 4 were assessed using Achenbach Child Behavior Checklist (CBCL/1.5~5) and their association with breastfeeding were analyzed using robust Poisson regression. Controlling false discovery rate was applied for multiple test correction. Results:Compared with bottle feeding, breastfeeding was a protective factor for depression in children ( RR=0.23, 95% CI: 0.05-0.98, q=0.048) when the duration was 4-5 months; for somatic complaints ( RR=0.36, 95% CI: 0.14-0.95, q=0.047) and anxiety ( RR=0.19, 95% CI: 0.06-0.62, q=0.010) with a breastfeeding duration of 6-11 months; and for depression ( RR=0.46, 95% CI: 0.25-0.83, q=0.039) and anxiety ( RR=0.12, 95% CI: 0.03-0.49, q=0.006) with a breastfeeding duration of 12 months and above. Compared with bottle feeding within 6 months, mixed feeding had a protective effect on somatic complaints ( RR=0.29, 95% CI: 0.13-0.64, q=0.026) and anxiety ( RR=0.18, 95% CI:0.07-0.52, q=0.002). Conclusions:The findings suggested that breastfeeding had a protective effect on behavioral problems at age 4 in children exposed to GDM. Women with GDM should be encouraged to breastfeed.

Objective    To compare the surgical efficacy of Da Vinci robot-assisted minimally invasive esophagectomy (RAMIE) and video-assisted minimally invasive esophagectomy (VAMIE) on esophageal cancer. Methods    Online databases including PubMed, the Cochrane Library, Medline, EMbase and CNKI from inception to 31, December 2019 were searched by two researchers independently to collect the literature comparing the clinical efficacy of RAMIE and VAMIE on esophageal cancer. Newcastle-Ottawa Scale was used to assess quality of the literature. The meta-analysis was performed by RevMan 5.3. Results    A total of 14 studies with 1 160 patients were enrolled in the final study, and 12 studies were of high quality. RAMIE did not significantly prolong total operative time (P=0.20). No statistical difference was observed in the thoracic surgical time through the McKeown surgical approach (MD=3.35, 95%CI –3.93 to 10.62, P=0.37) or in surgical blood loss between RAMIE and VAMIE (MD=–9.48, 95%CI –27.91 to 8.95, P=0.31). While the RAMIE could dissect more lymph nodes in total and more lymph nodes along the left recurrent laryngeal recurrent nerve (MD=2.24, 95%CI 1.09 to 3.39, P=0.000 1; MD=0.89, 95%CI 0.13 to 1.65, P=0.02) and had a lower incidence of vocal cord paralysis (RR=0.70, 95%CI 0.53 to 0.92, P=0.009). Conclusion    There is no statistical difference observed between RAMIE and VAMIE in surgical time and blood loss. RAMIE can harvest more lymph nodes than VAMIE, especially left laryngeal nerve lymph nodes. RAMIE shows a better performance in reducing the left laryngeal nerve injury and a lower rate of vocal cord paralysis compared with VAMIE.

Coronavirus disease 2019 (COVID-19) can increase the risk of thrombosis and arterial embolism events in patients. The more serious the condition, the higher the risk. Therefore, many academic groups at home and abroad have successively issued guidelines on the prevention and treatment of thrombosis in patients with COVID-19. Among them, American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19 (ASH guidelines) and its updates are newer and have more detailed recommendations on the application of anticoagulant drugs to prevent venous thromboembolism in acutely and critically ill patients with COVID-19. This review aims to provide reference for clinic through general viewing the ASH guidelines as well as other relevant guidelines at home and abroad.

Coronavirus disease 2019 (COVID-19) can increase the risk of thrombosis and arterial embolism events in patients. The more serious the condition, the higher the risk. Therefore, many academic groups at home and abroad have successively issued guidelines on the prevention and treatment of thrombosis in patients with COVID-19. Among them, American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19 (ASH guidelines) and its updates are newer and have more detailed recommendations on the application of anticoagulant drugs to prevent venous thromboembolism in acutely and critically ill patients with COVID-19. This review aims to provide reference for clinic through general viewing the ASH guidelines as well as other relevant guidelines at home and abroad.