Objective:To develop fluorescent nanoprobes with aggregation-induced emission characteristics and to systematically evaluate their optical properties, biosafety, anti-tumor activity, and imaging capability, thereby assessing their potential for early precision diagnosis and treatment of oral cancer in mice.Methods:Control probes (PEG@TPD) were prepared by encapsulating ( E)-4-(2-(4′-(1-phenyl-2,2-bis(4-methoxyphenyl)vinyl)biphenyl-4-yl)vinyl)-4-(dicyanomethylene)-4 H-chromene (TPD) using 1,2-distearoyl- SN-glycerol-3-phosphoethanolamine- N-polyethylene glycol 2000-maleimide as the carrier. Fluorescent nanoprobes (GE11-PEG@TPD) were subsequently fabricated by surface modification with the targeting GE11 peptide. The morphology and particle size of the nanoprobes were characterized by transmission electron microscopy and dynamic light scattering. The optical properties of the nanoprobes were analyzed using ultraviolet-visible spectrophotometry and fluorescence spectrophotometry. Mouse squamous carcinoma SCC-7 cells were randomly divided into six groups by the random number table method. The PBS, PEG@TPD, and GE11-PEG@TPD groups were not treated with light, while the PBS+L, PEG@TPD+L, and GE11-PEG@TPD+L groups were exposed to white light (25 W/cm 2, 10 min) at a nanoprobe concentration of 20 μg/ml (based on TPD concentration). Cell survival rate was assessed by the cell counting kit-8 assay. Cellular uptake, intracellular reactive oxygen species levels, and cytotoxicity were evaluated using laser scanning confocal microscopy. The apoptosis rate was evaluated by cell apoptosis assay. Twelve 6-week-old female C3H/HeN mice were randomly divided into two groups: PEG@TPD-1 group and GE11-PEG@TPD-1 group, with 6 mice in each group. Subcutaneous oral cancer models were established by injecting SCC-7 cell suspensions into the dorsal region of mice in two groups. Each mouse was intravenously administered 200 μl of PEG@TPD or GE11-PEG@TPD solution (1 mg/ml, based on TPD concentration). Tumor boundaries and scope were visualized using a small animal in vivo imaging system. At the optimal imaging time point, three mice from each group were euthanized, and major organs and tumor tissues were collected to measure probe accumulation. Statistical comparisons between two groups were performed using independent samples t-tests, while one-way or two-way analysis of variance was applied for multiple group comparisons. Results:Both PEG@TPD and GE11-PEG@TPD exhibited a relatively regular sphere, with average particle sizes of (92.76±8.80 and 117.50±6.40) nm, respectively. PEG@TPD showed two obvious absorption peaks at 352 and 444 nm. GE11 peptide showed a polypeptide characteristic absorption peak at 280 nm, GE11-PEG@TPD showed three characteristic absorption peaks at 280, 352 and 444 nm. Under dark conditions, cell survival rate remained above 80% even at a concentration of 160 μg/ml. After light irradiation, cell survival rate in the PEG@TPD+L group at 20 and 40 μg/ml [(68.2±5.2)% and (48.6±7.1)%] were higher than those in the GE11-PEG@TPD+L group [(55.0±2.8)% and (30.0±9.2)%], with statistically significant differences ( P<0.05, 0.01). At incubation time points of 2, 4, and 6 h, the relative fluorescence intensity of the GE11-PEG@TPD group (119.4±10.2, 192.9±14.2, and 234.1±4.8) were higher than those of the PEG@TPD group (98.6±7.5, 163.8±3.1, 204.6±11.2), with statistically significant differences (all P<0.05). The relative fluorescence intensity of the PEG@TPD+L and GE11-PEG@TPD+L group (68.5±4.7 and 86.8±10.0) were higher than those in the PBS, PEG@TPD, GE11-PEG@TPD, and PBS+L groups (6.1±8.0, 7.6±1.8, 4.7±4.2 and 21.1±7.6), with statistically significant differences (all P<0.01). And the difference between the GE11-PEG@TPD+L and PEG@TPD+L groups was also statistically significant ( P<0.05). Viable cell proportions in the PBS, PEG@TPD, GE11-PEG@TPD, and PBS+L groups all exceeded 95.0%, while those in the PEG@TPD+L and GE11-PEG@TPD+L groups decreased to (11.1±3.7)% and (4.3±1.1)%, respectively, with a statistically significant difference between them ( P<0.05). The apoptotic cell proportions in the PEG@TPD+L and GE11-PEG@TPD+L groups [(40.5±4.3)% and (55.3±7.4)%] were higher than those in the PBS, PEG@TPD, GE11-PEG@TPD, and PBS+L groups [(27.3±2.0)%, (28.2±1.9)%, (28.6±1.2)%, and (29.7±3.0)%], with statistically significant differences ( P<0.05, 0.01). Moreover, the difference between the GE11-PEG@TPD+L and the PEG@TPD+L groups was also statistically significant ( P<0.01). The mean fluorescence intensities of the GE11-PEG@TPD-1 group at 1, 3, 5, 8, and 24 h, as well as in ex vivo tumor tissues[(5.2±0.8, 5.9±0.7, 6.6±1.0, 7.9±0.6, 7.8±0.7 and 20.6±3.5)×10 6 p/s/cm 2/sr] were all higher than those in the PEG@TPD-1 group [(3.2±0.7, 4.2±0.7, 4.6±0.9, 5.1±0.9, 4.7±0.9 and 14.2±1.8)×10 6 p/s/cm 2/sr], with statistically significant differences ( P<0.05, 0.01). Conclusions:The fluorescent nanoprobes exhibit uniform particle size, high photostability, and good biocompatibility. They demonstrate significant tumor-killing effects at the cellular level and possess tumor-targeting capability in vivo, showing promising application potential for the early precision diagnosis and treatment of oral cancer.

Objective:To explore the feasibility and advantages of applying visualized thermosensitive color-changing bolus in postmastectomy radiotherapy (PMRT) for breast cancer.Methods:Forty patients with breast cancer treated with PMRT in the Second Affiliated Hospital of Soochow University from June 2023 to June 2024 were prospectively selected. They were randomly divided into test and control groups (also referred to as groups A and B, respectively), with 20 patients in each group. Group A, underwent two CT scans: the first scan without bolus (image A1) and the second scan with visualized thermosensitive color-changing bolus (image A2). They were treated with visualized thermosensitive color-changing bolus. Group B also underwent two CT scans: the first scan without bolus (image B1) and the second scan with conventional commercial bolus (image B2), and then were treated with conventional commercial bolus. In the radiotherapy planning, images A1 and A2 were designed as A1-Plan and A2-Plan, and A3-Plan was created by transferring the A1-Plan onto image A2. Images B1 and B2 were designed as B1-Plan and B2-Plan, and B3-Plan was created by transferring the B1-Plan onto image B2. The radiation fields and target optimization functions were identical. The dosimetric differences and skin toxicity reactions between different plans were compared.Results:In Group A, A1-Plan and A2-Plan manifested no statistically significant differences ( P > 0.05) in the doses to organs at risk (OARs), including the ipsilateral lung ( V5 Gy, V10 Gy, V20 Gy), heart ( Dmean), contralateral breast ( Dmean), and skin ( Dmax and Dmean), target homogeneity index (HI), conformity index (CI), prescription dose volume ( V50 Gy), depth of maximum dose ( Dmax), and monitor unit (MU). In Group B, B3-Plan compared to B1-Plan showed reduced V50 Gy (89.9% vs. 95%), HI (0.153 vs. 0.136), and CI (0.817 vs. 0.810), while the two plans displayed no statistically significant differences in doses to OARs. In contrast, A3-Plan and B3-Plan exhibited statistically significant differences ( t = 2.78, 2.29, -0.47, 0.51, 3.13, P < 0.05) in V50 Gy (94.05% vs. 89.90%), Dmax (5 665.4 cGy vs. 5 632.7 cGy), HI (0.148 vs. 0.163), CI (0.83 vs. 0.82), and skin Dmean (5 153.6 cGy vs. 5 048.2 cGy). Compared to the conventional commercial bolus of the same thickness, the visualized thermosensitive color-changing bolus yielded a significantly reduced air cavity volume (3 833 mm 3vs. 21 498 mm 3,t = -9.65, P < 0.05). Both groups experienced only grade I skin toxicity reactions. Conclusions:Compared to the conventional commercial bolus of the same thickness, the visualized thermosensitive color-changing bolus shows a more effective dosimetric distribution in terms of target coverage, HI, and CI, a higher fit to the skin, highly visualized air cavity, and higher positional repeatability in fractionated radiotherapy, demonstrating high practicality and safety.

Objective:To explore the feasibility and advantages of applying visualized thermosensitive color-changing bolus in postmastectomy radiotherapy (PMRT) for breast cancer.Methods:Forty patients with breast cancer treated with PMRT in the Second Affiliated Hospital of Soochow University from June 2023 to June 2024 were prospectively selected. They were randomly divided into test and control groups (also referred to as groups A and B, respectively), with 20 patients in each group. Group A, underwent two CT scans: the first scan without bolus (image A1) and the second scan with visualized thermosensitive color-changing bolus (image A2). They were treated with visualized thermosensitive color-changing bolus. Group B also underwent two CT scans: the first scan without bolus (image B1) and the second scan with conventional commercial bolus (image B2), and then were treated with conventional commercial bolus. In the radiotherapy planning, images A1 and A2 were designed as A1-Plan and A2-Plan, and A3-Plan was created by transferring the A1-Plan onto image A2. Images B1 and B2 were designed as B1-Plan and B2-Plan, and B3-Plan was created by transferring the B1-Plan onto image B2. The radiation fields and target optimization functions were identical. The dosimetric differences and skin toxicity reactions between different plans were compared.Results:In Group A, A1-Plan and A2-Plan manifested no statistically significant differences ( P > 0.05) in the doses to organs at risk (OARs), including the ipsilateral lung ( V5 Gy, V10 Gy, V20 Gy), heart ( Dmean), contralateral breast ( Dmean), and skin ( Dmax and Dmean), target homogeneity index (HI), conformity index (CI), prescription dose volume ( V50 Gy), depth of maximum dose ( Dmax), and monitor unit (MU). In Group B, B3-Plan compared to B1-Plan showed reduced V50 Gy (89.9% vs. 95%), HI (0.153 vs. 0.136), and CI (0.817 vs. 0.810), while the two plans displayed no statistically significant differences in doses to OARs. In contrast, A3-Plan and B3-Plan exhibited statistically significant differences ( t = 2.78, 2.29, -0.47, 0.51, 3.13, P < 0.05) in V50 Gy (94.05% vs. 89.90%), Dmax (5 665.4 cGy vs. 5 632.7 cGy), HI (0.148 vs. 0.163), CI (0.83 vs. 0.82), and skin Dmean (5 153.6 cGy vs. 5 048.2 cGy). Compared to the conventional commercial bolus of the same thickness, the visualized thermosensitive color-changing bolus yielded a significantly reduced air cavity volume (3 833 mm 3vs. 21 498 mm 3,t = -9.65, P < 0.05). Both groups experienced only grade I skin toxicity reactions. Conclusions:Compared to the conventional commercial bolus of the same thickness, the visualized thermosensitive color-changing bolus shows a more effective dosimetric distribution in terms of target coverage, HI, and CI, a higher fit to the skin, highly visualized air cavity, and higher positional repeatability in fractionated radiotherapy, demonstrating high practicality and safety.

Integrase inhibitors (INSTIs) are the newest class of antiretroviral drug which are available to people living with the human immunodeficiency virus (HIV). Since 2007, five types of INSTIs have been marketed: Raltegravir, Elvitegravir, Dolutegravir, Bictegravir and Cabotegravir, all of which were approved by the US Food and Drug Administration (FDA) for use in the initiation of antiretroviral therapy (ART) in treatment-na?ve individuals. Compared with other types of antiretroviral drugs, INSTIs have better efficacy and tolerability, so many countries around the world have listed INSTIs-containing regimens as the preferred regimen for HIV ART. In recent years, with the widespread use of INSTIs, some research data suggest that INSTIs may have some adverse effects (AEs), such as central nervous system symptoms, abnormal lipid metabolism, weight gain, abnormal liver and kidney function, etc. This review summarizes the current use of INSTIs in people living with the HIV, and highlights the clinical efficacy and their AEs among the five types of INSTIs in China.

Objective: To investigate the association between frailty and type 2 diabetes mellitus (T2DM) using a bidirectional two-sample Mendelian randomization (MR) analysis, so as to provide the evidence for the prevention and control of frailty and T2DM. Methods: Frailty status was assessed using the Fried Frailty Score (FFS), with aggregated data sourced from 386 565 European samples in the UK Biobank. The T2DM data were obtained from the summary results of genome-wide analysis published by the Diabetes Genetics Replication and Meta-analysis Consortium, excluding the UK Biobank data, including 455 313 European samples. Eligible single nucleotide polymorphism site were selected from the FFS and T2DM summary data as instrumental variables. The bidirectional MR analysis was performed using the inverse-variance weighted method. The heterogeneity was assessed using the modified Cochran Q test. The horizontal pleiotropy of instrumental variables was examined using MR-Egger regression. The robustness of the results was evaluated using the leave-one-out method. The bias was tested using funnel plot. Results: The forward MR analysis revealed a statistically significant association between increased FFS and an increased risk of T2DM (OR=2.280, 95%CI: 1.169-4.447). The reverse MR analysis showed a statistically significant association between T2DM and increased FFS (β=0.026, 95%CI: 0.012-0.041). Both bidirectional MR results were robust, with no horizontal pleiotropy of the instrumental variables was found (all P>0.5); and the funnel plots did not show significant basis. Conclusion The study found a bidirectional causal association between frailty and T2DM.

Objective:To investigate the impact of early blood glucose fluctuations after acute multiple injuries on post-traumatic stress disorder (PTSD).Methods:This study was a case-control study. From March 2022 to March 2023, patients with acute multiple injuries who were admitted to the ICU of the Affiliated Hospital of Xuzhou Medical University were selected. According to whether complicated with traumatic brain injury (TBI), the patients were divided into TBI group and non-TBI group. Early post-traumatic blood glucose fluctuations were observed, including stress-induced hyperglycemia (SIH), initial blood glucose value on admission, blood glucose extreme, short-term glycemic variability (GV) and other related indicators. The 72-hour glucose coefficient of variation (Glu-CV) was used to reflect short-term GV. After 1 month, the PTSD checklist for DSM-5 (PCL-5) was used to assess the patient's symptoms of PTSD. The patients were divided into PTSD group and non-PTSD group according to PCL-5 score ≥38. The differences in short-term glucose fluctuations in each groups were compared; the risk factors of PTSD were analyzed by logistic regression; the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of related indicators on the incidence of PTSD.Results:159 patients with acute multiple injuries were selected and defined as the TBI group ( n=94) and non-TBI group ( n=65). The incidence of PTSD, PCL-5 scale scores, the incidence of SIH and 72 h Glu-CV in the TBI group were significantly higher than the non-TBI group (all P<0.05). The incidence of SIH and 72 h Glu-CV in the PTSD group were significantly higher than the non-PTSD group (both P<0.05). Multivariate logistic regression analysis showed that 72 h Glu-CV ( OR=1.333, 95% CI: 1.028-1.727, P=0.030) was the independent risk factor for PTSD after acute multiple injuries, and the area under the ROC curve was 0.861 (95% CI: 0.789-0.933, P<0.001), the sensitivity was 62.9% and the specificity was 93.5%. Conclusion:Patients with acute multiple injuries with TBI are more likely to have early glucose fluctuations and develop PTSD, and increased short-term glucose variability is the independent risk factor for PTSD after acute multiple injuries.

Objective To comprehensively review the clinical research on the treatment of hyperlipidemia with traditional Chinese Medicine(TCM)through the evidence mapping,and to understand the distribution of evidence in this field. Methods Databases including CNKI,Wangfang,VIP,SinoMed,PubMed,Cochrane Library,and Embase were searched from January 2004 to December 2023 to collect clinical studies,systematic reviews/meta-analyses,guidelines and clinical pathways related to the treatment of hyperlipidemia with TCM. The results were analyzed and displayed in charts and graphs according to the screening criteria,and the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool and the Preferred Reporting Item for Systematic Review and Meta-analysis of Chinese herbal medicine (PRISMA-CHM) were used to evaluate the quality of the systematic review/meta-analysis. Results A total of 1223 studies were included in the analysis according to Population,Intervention,Comparison,Outcome and Study design(PICOS) principles,involving 920 RCTs,249 non-RCTs,49 systematic reviews/meta-analyses,and 5 guidelines/expert consensus. In recent years,the overall number of clinical research publications has shown a downward trend. Hyperlipidemia frequently occurs in middle-aged and elderly people,and age of onset tends to be younger. The sample size of randomized controlled studies is mostly concentrated in 60-300 cases. There are many types of clinical treatment regimens for the treatment of hyperlipidemia with TCM,among which TCM decoction (50.13％) and Chinese patent medicine (38.41％) account for a relatively high proportion,and TCM exercise therapy (0.51％) is the lowest treatment. Jiangzhi Decoction has attracted more attention in trial group of TCM decoction,while Xuezhikang Capsule has attracted more attention in trial group of Chinese patent medicine. In terms of methodological design,199 papers(21.63％) explicitly mentioned the method of generating random sequence,17 papers(1.85％) mentioned allocation concealment,37 papers (4.02％) mentioned blinding. The control group was dominated by the statins,including simvastatin and atorvastatin. The outcome indicators mainly include the total effective rate,TCM syndrome score,blood lipid level,coagulation index,and adverse reactions,while the attention of TCM characteristic efficacy,inflammation,oxidative stress,and vascular endothelial index were low. The methodological and reporting quality of the systematic review/Meta-analysis were generally not high. AMSTAR-2 evaluation was extremely low,and the average PRISMA-CHM score was 15. Conclusion TCM has certain advantages in the treatment of hyperlipidemia,but there is a lack of high-quality evidence-based proof,and more high-quality clinical studies are still needed to further provide evidence supports in the future. It has been suggested that more large-sample and multi-center clinical studies should be carried out in the future. We should formulate systematic reviews/Meta analysis and guidelines/expert consensus according to the guidelines of clinical practice issues,also consult international standards and regulations,enhance normativity and reliability to improve the quality of their evidence.

In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.

Objective:To analyze the application and regularity of acupoint selection of Sanyinjiao (SP 6) based on data mining.Methods:Search for literatures in CNKI, Wanfang, VIP, and Pubmed, the clinical researches of acupuncture on Sanyinjiao (SP 6) point were selected, according to the inclusion and exclusion criteria, and the retrieval period was from database construction to September 30th, 2021. Excel 2016, SPSS Statistics 25.0, SPSS Modeler 18.0 were used to perform descriptive analysis, association analysis and cluster analysis.Results:After literature screening, a total of 261 literatures were included, involving 73 kinds of diseases, mainly including mental and behavioral disorders, genitourinary diseases, endocrine and nutritional metabolism diseases and nervous system diseases. The most frequently used acupoints in Sanyinjiao (SP 6) compatibility are Zusanli (ST 36), Baihui (GV 20), Guanyuan (CV 4) and Taichong (LR 3), most of which focus on stomach meridian, conception channel, governor channel and bladder meridian. Seven categories were extracted among high-frequency acupoints by cluster analysis. The association rule analysis showed that the commonly used combination of Sanyinjiao (SP 6) were Zusanli (ST 36)-Sanyinjiao (SP 6), Baihui (GV 20)-Sanyinjiao (SP 6), and Guanyuan (CV 4)-Sanyinjiao (SP 6).Conclusions:Sanyinjiao (SP 6) is widely used in clinical application, and it is always compatible with stomach meridian, conception vessel, governor channel acupoints, especially those acupoints on the outer and inner meridians and the upper and lower parts. Sanyinjiao (SP 6) combined with other acupoints can treat diseases of multiple systems, such as insomnia, stroke, anxiety and depression, dysmenorrhea, infertility, etc. Clustering and association analysis found the core compatibility law of Sanyinjiao (SP 6), which can be used as a reference for clinical acupoint selection.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.