Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

Objective:To investigate the correlation between the expression of GLI1 and im-mune invasion and clinical prognosis in gastric cancer.To study the effect of GLI1 expression on drug resistance in gastric cancer.Methods:The expression difference of GLI1 in gastric cancer and normal tissues was analyzed by using TCGA database,and the effect of clinical features and GLI1 gene ex-pression level on prognosis of patients with gastric cancer was analyzed.The correlation between GLI1 gene expression and tumor immune cell infiltration in gastric cancer tissues was analyzed to explore its influence on drug resistance of chemotherapy drugs and targeted drugs.Clinical samples were collect-ed to analyze the difference of GLI1 expression in gastric cancer and paracancer tissues.Results:The expression of GLI1 in gastric cancer tissues was 1.7 times that in normal tissues,and the overall sur-vival and disease-free survival of patients with high expression are shorter than those with low ex-pression(P＜0.05).The interstitial score,immune score and abundance of immunoinfiltrating cells were higher in the high expression of GLI1 in gastric cancer tissues.High expression of GLI1 reduces drug sensitivity and is positively correlated with the expression of immune checkpoint markers PDCD1(P＜0.05).GLI1 expression was significantly increased in patients with subdifferentiated gastric cancer.Conclusions:GLI1 expression is associated with the prognosis and immune infiltration of patients with gastric cancer,and it may lead to poor prognosis of patients by regulating chemotherapy resis-tance,which may be a potential therapeutic target and molecular marker for gastric cancer.

OBJECTIVE To confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA) and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) in the treatment of OA based on high-throughput sequencing technology. METHODS Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation, bipedal balance difference experiment, mechanical foot reflex threshold, Micro-CT observation, and Safranin O-Fast Green staining. SMSCs and ACs were cultured in suitable concentration of drug-containing serum, and mRNA sequencing was performed on ACs in the control, model, and Jintiange capsules groups, as well as miRNA sequencing on SMSC-Exos. Differential expressed mRNAs and miRNAs were screened and target genes were predicted. The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes, and a miRNA-mRNA regulatory network was constructed using Cytoscape software. The expression trend analysis of common differential expressed genes was conducted, as well as the correlation analysis between differential expressed gene mRNA and miRNA, Micro-CT efficacy indicators, and differential expressed gene mRNA. RESULTS Under the pathological state of OA, the expression of miRNA-23a-3p, miRNA-342-3p, miRNA-146b-5p, miRNA-501-3p, and miRNA-214-3p were down-regulated, while miRNA-222-3p, miRNA-30e-3p, miRNA-676-3p, and miRNA-192-5p were up-regulated (P<0.05). The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules. There was a certain correlation between Micro-CT efficacy indicators, mRNA and miRNA. CONCLUSION Jintiange capsule has obvious efficacy in the treatment of OA, and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10, Ntn1, Il1b, Tgm2, Megf10, Il11, Cd40, Slc15a3, Pou2f2 and other genes.

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.

This study aimed to parallelly investigate the cardioprotective activity of Cinnamomi Ramulus formula granules(CRFG) and Cinnamomi Cortex formula granules(CCFG) against acute myocardial ischemia/reperfusion injury(MI/RI) and the underlying mechanism based on the efficacy of "warming and coordinating the heart Yang". Ninety male SD rats were randomly divided into a sham group, a model group, CRFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, and CCFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, with 15 rats in each group. The sham group and the model group were given equal volumes of normal saline by gavage. Before modeling, the drug was given by gavage once a day for 7 consecutive days. One hour after the last administration, the MI/RI rat model was established by ligating the left anterior descending artery(LAD) for 30 min ischemia followed by 2 h reperfusion except the sham group. The sham group underwent the same procedures without LAD ligation. Heart function, cardiac infarct size, cardiac patho-logy, cardiomyocyte apoptosis, cardiac injury enzymes, and inflammatory cytokines were determined to assess the protective effects of CRFG and CCFG against MI/RI. The gene expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain protein 3(NLRP3) inflammasome, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate specific proteinase-1(caspase-1), Gasdermin-D(GSDMD), interleukin-1β(IL-1β), and interleukin-18(IL-18) were determined by real-time quantitative polymerase chain reaction(RT-PCR). The protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD were determined by Western blot. The results showed that both CRFG and CCFG pretreatments significantly improved cardiac function, decreased the cardiac infarct size, inhibited cardiomyocyte apoptosis, and reduced the content of lactic dehydrogenase(LDH), creatine kinase MB isoenzyme(CK-MB), aspartate transaminase(AST), and cardiac troponin Ⅰ(cTnⅠ). In addition, CRFG and CCFG pretreatments significantly decreased the levels of IL-1β, IL-6, and tumor necrosis factor-α(TNF-α) in serum. RT-PCR results showed that CRFG and CCFG pretreatment down-regulated the mRNA expression levels of NLRP3, caspase-1, ASC, and downstream pyroptosis-related effector substances including GSDMD, IL-18, and IL-1β in cardiac tissues. Western blot revealed that CRFG and CCFG pretreatments significantly decreased the protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD in cardiac tissues. In conclusion, CRFG and CCFG pretreatments have obvious cardioprotective effects on MI/RI in rats, and the under-lying mechanism may be related to the inhibition of NLRP3/caspase-1/GSDMD signaling pathway to reduce the cardiac inflammatory response.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Interleukin-18 ; Myocardial Reperfusion Injury ; NLR Family, Pyrin Domain-Containing 3 Protein ; Tumor Necrosis Factor-alpha ; Myocardial Infarction ; Caspase 1

OBJECTIVE: To assess the safety and efficacy of Neuroform Atlas stent used in treatment of unruptured wide-neck intracranial aneurysms. METHODS: Clinical data of 62 patients with unruptured wide-neck intracranial aneurysms undergoing Neuroform Atlas stent-assisted coiling from August 2020 to September 2021 were retrospectively analyzed. There were 64 aneurysms in those 62 patients. Among them, 25 aneurysms were located at the bifurcation of M1 segment on middle cerebral artery, 16 at the anterior communicating artery, 10 at the C7 segment of internal carotid artery, 5 at the C6 segment of internal carotid artery, 4 at the apex of basilar artery, 3 at the A3 segment of anterior cerebral artery, and 1 at the M2 segment of middle cerebral artery. All the patients underwent Neuroform Atlas stent-assisted coiling, including 49 patients with single stent assisted coiling and 15 patients with dual stents assisted coiling (14"Y"style and 1"X"style). After the procedure, the immediate DSA was performed to evaluate the status of aneurysm occlusion and the parent artery patency. The clinical follow-up was performed 3 months after the operation and evaluated based on the modified Rankin Scale(mRS).DSA image was reviewed at 6 months after operation and Raymond grading scale was used to assess the status of aneurysm occlusion and the parent artery patency. RESULTS: A total of 62 patients with 64 aneurysms were all achieved technical success(100%).The immediate post-procedural Raymond scale was assessed, including Raymond Ⅰ in 57 aneurysms(89.1%, 57/64), Raymond Ⅱ in 6 aneurysms(9.3%, 6/64) and Raymond Ⅲ in 1 aneurysm(1.6%, 1/64). The peri-procedural complications rate was 4.8%(3/62), 2 patients developed intraoperative thrombosis and 1 patient suffered from local subarachnoid hemorrhage. Among them, 55 patients obtained 3 months clinical follow-up after operation and all the patients had good outcomes (mRS≤2), 50 patients with 52 aneurysms were followed up with DSA 6 months after operation, including Raymond Ⅰ in 45 aneurysms(86.5%, 45/52), Raymond Ⅱ in 4 aneurysms(7.7%, 4/52) and Raymond Ⅲ in 3 aneurysms(5.8%, 3/52). CONCLUSION Neuroform Atlas stent for the treatment of unruptured wide-neck intracranial aneurysms has high safety and good efficacy, and has its advantages over other traditional stents.
Humans ; Intracranial Aneurysm/etiology* ; Retrospective Studies ; Treatment Outcome ; Embolization, Therapeutic/methods* ; Stents/adverse effects* ; Cerebral Angiography

Pyroptosis is a programmed cell death initiated by the activation of caspases, which is involved in the development and progression of several cardiovascular diseases. The gasdermins, a protein family, are key executive proteins in the development of pyroptosis, which increase cell membrane permeability, mediate the release of inflammatory factors, and aggravate the inflammatory injury. Traditional Chinese medicine(TCM)has shown unique therapeutic advantages in cardiovascular diseases with multi-component and multi-target characteristics. Currently, the effective prevention and treatment of cardiovascular diseases based on the theory of pyroptosis become a new research hotspot in this field. Based on the theories of TCM and modern medicine, this study summarized the role of pyroptosis in cardiovascular diseases such as atherosclerosis, myocardial infarction, diabetic cardiomyopathy, hypertension, and myocarditis. The role of TCM, including active monomers, crude extracts, and compound preparations, in cardiovascular protection through the regulation of pyroptosis was also summarized, providing a theoretical basis for the clinical prevention and treatment of cardiovascular diseases by TCM.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Cardiovascular Diseases/prevention & control* ; Pyroptosis ; Myocardial Infarction/drug therapy*

Objective:To investigate the value of brain functional connectivity density (FCD) derived from resting-state functional magnetic resonance imaging (rs-fMRI) in differentially diagnosing 2 subtypes of Parkinson's disease (PD): tremor dominant (TD) and non-tremor dominant (nTD), as well as its correlation with clinical symptom scores.Methods:A retrospective analysis was performed; 45 PD patients (25 with TD and 20 with nTD), admitted to Department of Neurology, Drum Tower Hospital Affiliated to Medical School of Nanjing University were chosen; and 24 middle-aged and elderly volunteers matched in age, gender and years of education at the same time were chosen as normal controls (NCs). The rs-fMRI data were collected and FCD map of the whole brain was computed. The FCD differences in whole brain and brain regions enjoying different FCD were compared among the 3 groups. ROC curve was used to analyze the differential diagnostic efficacy of FCD in brain regions enjoying different FCD in TD and nTD. Correlations of FCD in brain regions enjoying different FCD with disease course, Hoehn-Yahr (H-Y) grading, unified Parkinson's disease rating scale (UPDRS) III scores, tremor scores and non-tremor scores were analyzed by Pearson or Spearman correlation analyses.Results:Brain regions enjoying different FCD among the TD, nTD, and NC groups were the right lingual gyrus, right orbital medial frontal gyrus, right insula, left superior temporal gyrus, left insula, right anterior central gyrus, left posterior central gyrus, right medial and paracingulate gyrus, and left angular gyrus. FCD in the right orbital medial frontal gyrus and left angular gyrus of TD group was significantly higher than that in the nTD group ( P<0.05); while FCD in the right insula, right anterior central gyrus, left posterior central gyrus and right medial and paracingulate gyrus of TD group was significantly lower than that in the nTD group ( P<0.05). Area under the curve of combined application of FCD in brain regions enjoying different FCD in differentially diagnosing TD and nTD was 0.842, with sensitivity and specificity of 80.0%. FCD in the left superior temporal gyrus and left posterior central gyrus was positively correlated with H-Y grading ( P<0.05), while FCD in the left angular gyrus was negatively correlated with H-Y grading ( P<0.05). FCD in the left superior temporal gyrus was positively correlated with UPDRS III scores ( P<0.05). FCD in the right lingual gyrus, right insula, left insula, right anterior central gyrus, left posterior central gyrus, right medial and paracingulate gyrus was negatively correlated with tremor scores ( P<0.05). FCD in the left superior temporal gyrus, right medial and paracingulate gyrus was positively correlated with non-tremor scores ( P<0.05), whereas that in the left angular gyrus was negatively correlated with non-tremor scores ( P<0.05). Conclusion:Abnormalities in FCD exist in certain brain regions of PD patients, with disparities between TD and nTD. Combined application of FCD in brain regions enjoying different FCD can effectively differentiate TD and nTD, and this FCD is also partially correlated with the symptom scores of PD patients.

Objective:To investigate the clinical effects of expanded flaps in reconstructing scar contracture deformities in the face and neck after extensive burns.Methods:A retrospective observational study was conducted. From May 2016 to September 2022, 17 patients with scar contracture deformities in the face and neck after extensive burns were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital, including 13 males and 4 females, aged 23 to 55 years, with 3 patients having degree Ⅱ cervical contracture, 14 patients having degree Ⅲ cervical contracture, and 12 patients having facial scar contracture deformity. In the first stage, 34 rectangular skin and soft tissue expanders (hereinafter referred to as expanders) with rated capacity of 100-600 mL were inserted into the face, chest, shoulder, and abdomen, and then the normal saline was injected for expansion. In the second stage, the scar tissue was removed and the contracture was released to correct the deformity. Two expanded facial flaps were transplanted in local fashion, 17 expanded flaps were transplanted in pedicled fashion, and 15 expanded flaps were freely transplanted to repair the secondary wounds after release, with artery pressurization was performed in 7 flaps. Indocyanine green fluorescence imaging was used to evaluate the arterial blood perfusion and venous return of the flaps during transplantation. The incision area of 32 flaps except 2 facial flaps was 10 cm×8 cm-36 cm×16 cm. The wounds of 31 flap donor sites were closed by direct suture, and the wound of 1 flap donor site was repaired by autologous split-thickness scalp transplantation. The skin condition of inserted place, expansion time, and total amount of normal saline injection of expanders, complications of skin and soft tissue expansion surgery, and survival of flap after the second stage surgery were observed and recorded. The long-term face and neck reconstruction effect and recovery of flap donor area were followed up. At the last follow-up, the 5-level Likert scale was used to evaluate the efficacy satisfaction of patients.Results:Of the 34 expander inserted places in 17 patients, 22 places were superficial scar skin after deep partial-thickness burns, 8 places were superficial scar skin after multiple skin donations, and 4 places were normal skin. After 4 to 15 months of expansion, the total normal saline injection volume was 238 to 2 000 mL, with no complications occurred. After the second stage surgery, the distal part of 2 pedicled flaps was partially necrotic, and the necrotic wounds were healed after flap dressing and free transplantation of contralateral expanded triangular flaps, respectively; the other flaps survived completely. During 6 to 18 months of follow-up, except for 2 expanded paraumbilical flaps and 1 expanded groin flap, which were bloated and improved by flap thinning, the appearance and texture of the other flaps were good, and all the flap donor sites recovered well. At the last follow-up, the face and neck scar contracture deformities were significantly improved in all patients, and the satisfaction of curative effect of patient was very satisfactory in 8 patients and relatively satisfactory in 9 patients.Conclusions:The expanded flaps of chest, abdomen, and other parts, combined with local advance, pedicled, and free transplantation, can effectively reconstruct scar contracture deformities in the face and neck after extensive burns, restore the function of operative area and improve the appearance simultaneously, with high degree of patient satisfaction, which is worthy of promotion in clinic.

OBJECTIVES: To investigate the prevalence of diabetes mellitus (DM) among Uygur children in Hotan Prefecture of Xinjiang, China, as well as the factors influencing the development of DM. METHODS: The cluster random sampling method was used to select 5 308 children, aged 4-18 years, from the middle and primary schools and kindergartens in Hotan Prefecture of Xinjiang. The survey methods included questionnaire survey and the measurement of height and weight. All subjects were tested for fasting fingertip blood glucose to investigate the prevalence of DM and impaired fasting glucose (IFG). RESULTS: A total of 5 184 valid questionnaires were collected. Fourteen children (0.27%) were found to have DM, among whom 8 had type 1 DM, 2 had type 2 DM, and 4 had unclassified DM. Twenty-nine children (0.56%) were found to have IFG. There was no significant difference in the prevalence rate of DM and IFG between boys and girls (P>0.05). The prevalence rate of DM was 0.18% in the 4-<10 years group, 0.47% in the 10-<15 years group, and 0.07% in the 15-18 years group (P=0.072).The prevalence rate of IFG in the above three age groups was 0.18%, 0.94%, and 0.42%, respectively, with a significant difference among groups (P=0.007). The proportion of family history of DM and the proportion of overweight/obesity in children with DM were significantly higher than those in children without DM (P<0.05), while the proportion of children with DM who preferred coarse grains was significantly lower than that in children without DM (P<0.05). CONCLUSIONS The prevalence of DM and IFG in Uyghur children in Hotan Prefecture of Xinjiang is relatively low. There is no significant difference in the prevalence of DM among children of different genders or age groups, but the prevalence of IFG in children of different age groups is different. A family history of DM, overweight or obesity, and low intake of coarse grains might be associated with the development of DM.
Adolescent ; Blood Glucose ; Child ; Child, Preschool ; China/epidemiology* ; Female ; Humans ; Male ; Pediatric Obesity ; Prediabetic State/epidemiology* ; Prevalence ; Risk Factors