AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.

OBJECTIVE To investigate the pharmacokinetic characteristics of crossbow microemulsion in rabbit skin.METH-ODS The concentrations of chlorogenic acid,benzoyl new aconitine,periplocin and new aconitine were determined by UPLC.The effects of temperature,perfusion speed and mass concentration on the recovery rate of the probe were investigated by incremental and decrement methods,the changes of multi-component content in the dialysate at different time points after transdermal administration of crossbow microemulsion were determined by UPLC,and DAS 2.0 software was used to process the data.RESULTS The recovery rate of the probe increased with increasing temperature,and the higher the flow rate,the lower the recovery rate.The pharmacokinetic parameters of chlorogenic acid,benzoyl new aconitine,periplocin and new aconitine in microemulsion Cmax were(3.24±0.39)(1.04±0.29)(4.78±2.15)(2.86±0.55)μg·mL-1,respectively,and in AUC0-∞ were(52.42±30.84)(7.70±3.73)(42.23±13.93)(22.68±12.51)h·mg·mL-1,respectively.CONCLUSION A real-time in vivo microdialysis sampling technique was first used and a UPLC detection technique was established to study the skin pharmacokinetics of multi-components of crossbow microe-mulsion after transdermal administration,which provides a reference for the follow-up investigation and application of crossbow microe-mulsion.

OBJECTIVE To prepare Lanqin extract/cyclodextrin complexes for probing its effects of different kinds of cyclodextrins on the taste-masking. METHODS Bitter compounds in the extracts were performed on ion exchange resin adsorption combined with HPLC. The formulations of complexes were screened by human taste panel method. The complexes were prepared by spray-drying and characterized through scanning electron microscope, differential scanning calorimetry, and hygroscopicty test. Moreover, the in vitro bitter taste perception of complexes was evaluated by electronic tongue and further valuation the credibility of the results was conducted on human gustatory sensation tests. RESULTS The sulfobutylether-β-cyclodextrin-based combinational formulation with multiple cyclodextrins could significantly inhibit the bitter taste of the extract which mainly caused by its alkaline constituents at a lower dosage. The results of electron scanning microscopy, differential scanning calorimetry, and hygroscopicity indicated that the Lanqin extract and cyclodextrin in the complex may form inclusion complexes rather than physical mixtures. The results of electronic tongue and human gustatory sensation tests showed that, compared with the extract suggested the taste characteristics of the optimal complexes was similar to corresponding excipient while the bitterness significantly reduced. CONCLUSION The Lanqin extract/cyclodextrin complexes prepared in this study are suitable for industrial production for its good flavour, less total amount of cyclodextrins, and simple process. The present study has important significance for the development of related taste masking products of Lanqin.

Objective To investigate the effect of early postoperative abnormal blood glucose on the short-term prognosis of non-small cell lung cancer(NSCLC),and to analyze the clinical characteristics and risk factors related to poor early prognosis.Methods A total of 897 patients with NSCLC who underwent thoracoscopic surgery in Huadong Hospital,Fudan University from Jan 2020 to Aug 2021 were divided into hyperglycemia(HG)group(>7.8 mmol/L)and normal blood glucose(NG)group(≤7.8 mmol/L and≥3.9 mmol/L)according to the early postoperative blood glucose values.Additionally,the patients were divided into higher blood glucose fluctuation group(≥4 mmol/L)and the group with lower blood glucose fluctuation(<4 mmol/L)basing on the fasting blood glucose.Using Logistic regression models,column line charts,ROC curves and other methods,we aimed to clarify the impact of early postoperative blood glucose abnormalities on short-term prognosis,explore clinical characteristics associated with poor short-term outcomes,identify other high-risk factors,and establish relevant risk prediction models.Results Compared with the NG group,the incidence of postoperative pneumonia,thromboembolism,ICU admission rate,total length of hospital stay and hospital cost were significantly higher in the HG group(P<0.05).Higher blood glucose fluctuation group had a greater risk of ICU admission(P=0.003).Logistic regression analysis showed that age,preoperative fasting glucose,white blood cell count and cytokeratin 19 fragment antigen 21-1(CYFRA21-1)were risk factors for postoperative hyperglycemia(P<0.05).Contrary to the effect of BMI,diabetes,male patients,higher blood glucose fluctuation,white blood cell count and age were the risk factors for postoperative adverse events(P<0.05).The AUC of the column line chart model was 0.661(95%CI:0.624-0.698),indicating good discriminative ability for predicting poor short-term prognosis postoperatively.Calibration curves also demonstrated good consistency between predicted and actual probabilities.Conclusion Early postoperative blood glucose fluctuations independently impact the short-term prognosis of thoracoscopic NSCLC patients.Blood glucose combined with gender,BMI,white blood cell count,age and diabetes history can serve as predictive factors for poor short-term prognosis postoperatively.Additionally,a column line chart constructed based on these factors may aid clinicians in early intervention for NSCLC patients with indications.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the effect and mechanism of tetramethylpyrazine(TMP)on cognitive function in mice with post-traumatic stress disorder(PTSD).Methods The mice were randomly divided into normal group,model group and experimental group.Except for the normal group,the PTSD mouse model was established by single prolonged stress(SPS).The experimental group was intraperitoneally injected with 10 mg·kg-1 TMP,and the normal group and the model group were intraperitoneally injected with an equal amount of 0.9％NaCl.The Morris water maze,open field and elevated plus maze tests were used to evaluate the cognitive behavior of the mice.The apoptosis of neurons was detected by Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).The expression of ionized calcium binding adapter molecule-1(Iba-1)protein was detected by immunofluorescence(ICC).The content of oxidative stress inflammatory factors was detected by enzyme-linked immunosorbent assay(ELISA).Results The escape latency of the normal group,model group,and TMP group were(56.50±9.89),(87.16±10.48)and(68.63±10.19)s,respectively;the corner residence time of the open field were(190.37±40.64),(260.39±40.54)and(218.63±38.27)s,respectively;the apoptosis rates were(18.28±2.35)％,(39.36±3.65)％and(30.74±3.58)％,respectively;the fluorescence intensities of Iba-1 were(8.01±2.23)％,(50.87±7.31)％and(7.49±1.41)％;malondialdehyde contents were(5.46±0.95),(12.98±2.06)and(8.31±1.28)nmol·mg-1,respectively;tumor necrosis factor-α contents were(53.59±9.91),(115.46±11.53)and(74.38±10.77)pg·mL-1,respectively.The above indexes in the normal group and the experimental group were statistically significant compared with the model group(P＜0.05,P＜0.01).Conclusion TMP can improve the cognitive function of PTSD mice,and the mechanism may be related to the regulation of inflammation and oxidative stress.

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.
Humans ; Male ; Mice ; Animals ; Orchitis ; Uropathogenic Escherichia coli/metabolism* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Macrophages/metabolism* ; Phenotype ; Infertility, Male/metabolism*

BACKGROUND: Studies have shown that the incidence and severity of corona virus disease 2019 (COVID-19) in patients with lung cancer are higher than those in healthy people. At present, the main anti-tumor treatments for lung cancer include surgery, immunotherapy, chemotherapy, radiotherapy, targeted therapy and anti-angiogenesis therapy. While the effects of different anti-tumor treatments on the occurrence and severity of COVID-19 pneumonia are not uniform. Therefore, we aimed to describe clinical characteristics and antitumor therapy of patients with lung cancer and COVID-19 pneumonia, and examined risk factors for severity in this population. METHODS: From December 1, 2022 to February 15, 2023, a retrospective study was conducted in 217 patients diagnosed with COVID-19 and pathologically confirmed lung cancer in the Jinling Hospital. We collected data about patients' clinical features, antitumor treatment regimen within 6 months, and the diagnosis and treatment of COVID-19. Risk factors for occurrence and severity of COVID-19 pneumonia were identified by univariable and multivariable Logistic regression models. RESULTS: (1) Among the 217 patients included, 51 (23.5%) developed COVID-19 pneumonia, of which 42 (82.4%) were classified as medium and 9 (17.6%) were classified as severe; (2) Univariate and multivariate analysis revealed overweight (OR=2.405, 95%CI: 1.095-5.286) and intrapulmonary focal radiotherapy (OR=2.977, 95%CI: 1.071-8.274) are risk factors for increasing occurrence of COVID-19 pneumonia, while other therapies are not; (3) Chronic obstructive pulmonary disease (COPD) history (OR=7.600, 95%CI: 1.430-40.387) was more likely to develop severe pneumonia and anti-tumor therapies such as intrapulmonary focal radiotherapy, chemotherapy, targeted therapy and immunotherapy did not increase severity. CONCLUSIONS Intrapulmonary focal radiation therapy within 6 months increased the incidence of COVID-19 pneumonia, but did not increase the severity. However, there was no safety concern for chemotherapy, targeted therapy, surgery and immunotherapy.
Humans ; COVID-19 ; Retrospective Studies ; Lung Neoplasms/drug therapy* ; Incidence ; Pneumonia/etiology*

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ² analysis, and a paired χ² test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ²=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ²=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ²=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ²=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ²=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.