Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the therapeutic efficacy and disruptive effects of Meropenem（MEM）-loaded microbubbles（MBs）combined with ultrasound targeted microbubble destruction（UTMD）technology on Escherichia coli and its biofilm.Methods:MEM-MBs were prepared using the thin-film hydration method，and their characterization was assessed using a Zeta potential analyzer，with morphological observations conducted under an optical microscope. An in vitro biofilm model of periprosthetic joint infection（PJI）caused by Escherichia coli was constructed，and the morphology of the biofilm and the distribution of MEM-MBs in the bacterial biofilm were observed under a laser confocal microscope after staining the biofilm with SYTO59 staining and DIL staining for Microbubbles. The biofilm morphology and the distribution of MEM-MBs in bacterial biofilm were observed under laser confocal microscope. The biofilms were randomly divided into 5 groups using a random number table：control，Meropenem（MEM），MEM-MBs，UTMD，and MEM-MBs+UTMD，with 12 samples per group. After applying the respective interventions，scanning electron microscopy（SEM）and laser scanning confocal microscopy（LSCM）were employed to observe the effects on the morphology and structure of Escherichia coli and its biofilm. Crystal violet staining was utilized to determine and compare the biofilm density among groups using a microplate reader. LSCM was also used to observe the biofilm thickness，while both LSCM and spread plate counting were employed to assess bacterial viability differences across groups.Results:①MEM-MBs meeting the experimental requirements were successfully constructed.②A dense Escherichia coli biofilm visible under both the naked eye and LSCM was established，with a thickness of（10.61 ± 0.17）μm and a proportion of dead bacteria within the biofilm of（16.8 ± 0.8）%.③MEM-MBs were observed to penetrate into all layers of the biofilm using LSCM.④The results of crystal violet staining showed a decreasing trend in the biofilm density of the control group，the MEM group，the MEM-MBs group，the UTMD group，and the MEM-MBs+UTMD group. There was no significant difference between the MEM group and the MEM-MBs group（ P＞0.05），while there was a significant difference in biofilm density between the other groups，as revealed by pairwise comparison（all P＜0.05）.⑤UTMD technique and MEM-MBs+UTMD could significantly disrupt the biofilm of Escherichia coli. LSCM results showed that，compared to the control group，the thickness of the biofilm was reduced in all other groups，with only the UTMD group and the MEM-MBs+UTMD group showing an increase in porosity（both P＜0.05）. In comparison with the MEM group and the MEM-MBs group，the UTMD group showed an increase in porosity，while the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05）. Additionally，compared to the UTMD group，the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05），based on laser confocal microscopy results.⑥The results of the plate counting and LSCM showed that，compared with the control group，clump counts decreased，and the proportion of dead cells increased in the MEM group，the MEM-MBs group，and the MEM-MBs+UTMD group（all P＜0.05）. Compared with MEM group and MEM-MBs group，the clump counts of UTMD group increased，the proportion of dead cells decreased（all P＜0.05）；the clump counts of MEM-MBs+UTMD group decreased，and the proportion of dead cells increased（all P＜0.05）.Compared with UTMD group（all P＜0.05），the clump counts of MEM-MBs+UTMD group decreased，while the proportion of dead cells increased（all P＜0.05）.⑦The results of scanning electron microscopy revealed that the network structure of Escherichia coli was completely destroyed in the MEM-MBs+UTMD group. Conclusions:UTMD technology combined with MEM-MBs exerts a significant disruptive effect on the morphology and structure of Escherichia coli biofilm and significantly enhances bactericidal efficacy.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the therapeutic efficacy and disruptive effects of Meropenem（MEM）-loaded microbubbles（MBs）combined with ultrasound targeted microbubble destruction（UTMD）technology on Escherichia coli and its biofilm.Methods:MEM-MBs were prepared using the thin-film hydration method，and their characterization was assessed using a Zeta potential analyzer，with morphological observations conducted under an optical microscope. An in vitro biofilm model of periprosthetic joint infection（PJI）caused by Escherichia coli was constructed，and the morphology of the biofilm and the distribution of MEM-MBs in the bacterial biofilm were observed under a laser confocal microscope after staining the biofilm with SYTO59 staining and DIL staining for Microbubbles. The biofilm morphology and the distribution of MEM-MBs in bacterial biofilm were observed under laser confocal microscope. The biofilms were randomly divided into 5 groups using a random number table：control，Meropenem（MEM），MEM-MBs，UTMD，and MEM-MBs+UTMD，with 12 samples per group. After applying the respective interventions，scanning electron microscopy（SEM）and laser scanning confocal microscopy（LSCM）were employed to observe the effects on the morphology and structure of Escherichia coli and its biofilm. Crystal violet staining was utilized to determine and compare the biofilm density among groups using a microplate reader. LSCM was also used to observe the biofilm thickness，while both LSCM and spread plate counting were employed to assess bacterial viability differences across groups.Results:①MEM-MBs meeting the experimental requirements were successfully constructed.②A dense Escherichia coli biofilm visible under both the naked eye and LSCM was established，with a thickness of（10.61 ± 0.17）μm and a proportion of dead bacteria within the biofilm of（16.8 ± 0.8）%.③MEM-MBs were observed to penetrate into all layers of the biofilm using LSCM.④The results of crystal violet staining showed a decreasing trend in the biofilm density of the control group，the MEM group，the MEM-MBs group，the UTMD group，and the MEM-MBs+UTMD group. There was no significant difference between the MEM group and the MEM-MBs group（ P＞0.05），while there was a significant difference in biofilm density between the other groups，as revealed by pairwise comparison（all P＜0.05）.⑤UTMD technique and MEM-MBs+UTMD could significantly disrupt the biofilm of Escherichia coli. LSCM results showed that，compared to the control group，the thickness of the biofilm was reduced in all other groups，with only the UTMD group and the MEM-MBs+UTMD group showing an increase in porosity（both P＜0.05）. In comparison with the MEM group and the MEM-MBs group，the UTMD group showed an increase in porosity，while the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05）. Additionally，compared to the UTMD group，the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05），based on laser confocal microscopy results.⑥The results of the plate counting and LSCM showed that，compared with the control group，clump counts decreased，and the proportion of dead cells increased in the MEM group，the MEM-MBs group，and the MEM-MBs+UTMD group（all P＜0.05）. Compared with MEM group and MEM-MBs group，the clump counts of UTMD group increased，the proportion of dead cells decreased（all P＜0.05）；the clump counts of MEM-MBs+UTMD group decreased，and the proportion of dead cells increased（all P＜0.05）.Compared with UTMD group（all P＜0.05），the clump counts of MEM-MBs+UTMD group decreased，while the proportion of dead cells increased（all P＜0.05）.⑦The results of scanning electron microscopy revealed that the network structure of Escherichia coli was completely destroyed in the MEM-MBs+UTMD group. Conclusions:UTMD technology combined with MEM-MBs exerts a significant disruptive effect on the morphology and structure of Escherichia coli biofilm and significantly enhances bactericidal efficacy.

Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensi-tivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen"green"natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression.Considering the high GST levels in HCC patients,this compound demon-strated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

Objective To investigate the relationship between cognitive impairment and sleep parameters in acute ischemic stroke patients with obstructive sleep apnea(OSA).Methods A total of 343 patients with acute ischemic stroke and OSA were selected.The cognitive function was assessed using the simple mental state examination scale(MMSE).Patients were divided into the stroke with OSA and cognitive impairment group(MMSE＜27 points,n=119)and the stroke with OSA without cognitive impairment group(MMSE≥27 points,n=224).General data,TOAST etiological classification and distribution of cerebral infarction lesions were collected.The intelligent sleep monitoring system was used to calculate apnea hypopnea index(AHI)and evaluate OSA.Objective sleep monitoring parameters were collected at night.Sleep monitoring was conducted within 24 h of admission and continuous monitoring for≥3 nights.Continuous monitoring duration≥7 h every night to obtain night sleep structure parameters.Multifactor Logistics regression was used to analyze the relationship between cognitive impairment and sleep parameters in stroke patients with OSA.Results Compared with the stroke with OSA without cognitive impairment group,the proportion of age,diabetes history and HHcy history,the proportion of patients with infarct lesions located in frontal,temporal,parietal,occipital,thalamus,basal ganglia,brainstem and hemioval center increased in the stroke with OSA and cognitive impairment group,and the number of years of education decreased,the number of waking times,the proportion of light sleep and AHI increased,the nighttime sleep efficiency and deep sleep period decreased(P＜0.05).Logistics regression analysis showed that after controlling for years of education,age and other interference factors,nighttime sleep efficiency and AHI were strongly associated with cognitive impairment in acute ischemic stroke patients with OSA(P＜0.05).The increased nighttime sleep efficiency was protective factor for cognitive impairment,and increased AHI was risk factor for cognitive impairment.Conclusion Cognitive impairment in acute ischemic stroke patients with OSA is closely related to sleep parameters,in which the increased sleep efficiency at night is a protective factor for cognitive impairment,and the increased AHI is a risk factor.

CUDC-101, an effective and multi-target inhibitor of epidermal growth factor receptor (EGFR), histone deacetylase (HDAC), and human epidermal growth factor receptor 2 (HER2), has been reported to inhibit many kinds of cancers, such as acute promyelocytic leukemia and non-Hodgkin's lymphoma. However, no studies have yet investigated whether CUDC-101 is effective against myeloma. Herein, we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma (MM) cell lines and induces cell apoptosis in a time- and dose-dependent manner. Moreover, CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase (PI3K) and HDAC, and regulated the cell cycle G2/M arrest. Moreover, we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug. Bortezomib is one of the important drugs in MM treatment, and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib. The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; Bortezomib/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; ErbB Receptors/antagonists & inhibitors* ; G2 Phase Cell Cycle Checkpoints ; Histone Deacetylase Inhibitors/pharmacology* ; Histone Deacetylases/metabolism* ; M Cells ; Multiple Myeloma/drug therapy*

Background::Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achieving the new target of 95-95-95-95 by 2025. This study reported the characteristics of newly diagnosed primary HIV-1 infection in Shenzhen.Methods::This is a real-world retrospective study. Eighty-seven newly diagnosed primary HIV-1-infected patients were recruited from January 2021 to March 2022 at the Third People’s Hospital of Shenzhen. Demographic, epidemiological, diagnostic, drug resistance, and medical data were described and analyzed.Results::Overall, 96.6% (84/87) of the newly identified primary HIV-1-infected patients were male, including 88.5% (77/87) men have sex with men (MSM), with a median age of 29.0 years (Q 1-Q 3: 24.0-34.0 years); of these, 85.1% (74/87) reported high-risk sexual behaviors with casual partners. The rate of condom usage was only 28.7% (25/87). The overall rate of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) was 8.0% (7/87, including 4 PrEP and 3 PEP cases) around the potential exposure, although 41.4% of the patients had prior awareness of such interventions. Moreover, only 19.5% (17/87) had previously used PrEP or PEP. Of those, 58.8% (10/17) of the patients obtained drugs from the internet, and only 35.3% (6/17) reported good compliance. A total of 54.0% (47/87) of subjects were diagnosed by the HIV nucleic acid test. Acute retroviral syndrome appeared in 54.0% (47/87) of patients. The prevalence of transmitted drug resistance (TDR) mutation was 33.9% (19/56), including 6 (10.7%) against nucleoside reverse transcriptase inhibitor (NRTI) plus non-nucleoside reverse transcriptase inhibitor (NNRTI), 8 (14.3%) against NNRTI, and 5 (8.9%) against protease inhibitor (PI) only. Conclusions::Owing to the low utilization rate and incorrect usage of PrEP and PEP, massive efforts are needed to promote HIV-preventive strategies in the MSM population. The extremely high prevalence of TDR mutation in this population implies the need for future pretreatment drug resistance surveillance.

Objective:To investigate the efficiency, safety and complication of 0.7 mg dexamethasone sustained release agent (Ozurdex ?) vitreous cavity implantation for macular edema secondary to vitrectomy. Methods:A total of 15 patients (16 eyes) were included in this retrospective case series study. There were 7 males (8 eyes) and 8 females (8 eyes). Age ranged from 47 to 72 years old with an average age of (60.2±8.6)years. Among them, 8 cases were diabetic retinopathy (6 cases combined cataract surgery). 4 cases were silicone oil removal after retinal detachment surgery (all combined cataract surgery). 2 cases were epi-macular membrane (all combined with cataract surgery) and 1 case was vitreous hemorrhage (combined with cataract surgery). Ozurdex ? was implanted for macular edema after vitrectomy. The number of implantation was from 1 to 3 times (mean 1.67 times). The follow-up time was from 3 to 12 months, with an average of (7.33±3.50)months. Results:The best corrected visual acuity (BCVA) was improved in 10 cases (11 eyes), unchanged in 4 cases and decreased in 1 case within 3 months after Ozurdex ? implantation in the 15 cases (16 eyes). The macular edema was significantly improved in all cases. The central macular thickness (CMT) measured by optical coherence tomography (OCT) was from 350 to 1 370 γm before surgery with average thickness (621.60±235.48)γm, and the CMT postoperative was 118 to 556 γm with average thickness (269.87±118.14)γm, with statistically significant difference ( P<0.001). Cataract was not progressive after Ozurdex ? implantation. Macular edema was recurrent in 7 cases after first implantation and stable for additional 1-2 injections. Intraocular pressure elevation occurred in 3 cases 1 to 2 months after implantation with the highest intraocular pressure of 36 mmHg, which were controlled by local anti-glaucoma eye drops. Drugs entered into the anterior chamber in 2 cases and was taken out in 1 case. Conclusions:The efficiency of Ozurdex ? vitreous cavity implantation is definite and the complications are controllable, so it is a safe and effective method to treat macular edema after vitrectomy.