Objective To explore the influences of long-chain noncoding RNA DHRS4-AS1 (lncRNA DHRS4-AS1) on the proliferation, invasion, migration, and apoptosis of thyroid cancer (TC) cells by regulating the microRNA-221-3p (miR-221-3p)/suppressor of cytokine signaling 3 (SOCS3) signaling axis. Methods Quantitative real-time PCR (qRT-PCR) was applied to detect the expression of lncRNA DHRS4-AS1, miR-221-3p, and SOCS3 mRNA in TC cell lines, and the optimal cell line was selected for subsequent experiments. FTC-133 cells were divided into five groups: control group, pcDNA-NC group, DHRS4-AS1 group, DHRS4-AS1 combined with agomir NC group, and DHRS4-AS1 combined with miR-221-3p-agomir group. Transfection efficiency was assessed using qRT-PCR. Dual luciferase reporter assays were applied to verify the targeting interaction between lncRNA DHRS4-AS1, SOCS3, and miR-221-3p. Western blot analysis was used to detect the expression of SOCS3 in FTC-133 cells. EdU method was used to measure cell proliferation. Flow cytometry was applied to measure the apoptosis of FTC-133 cells. Scratch experiment was applied to measure the migration of FTC-133 cells. Transwell chamber was applied to detect the invasion of FTC-133 cells. Nude mouse transplantation tumor experiment was used to observe the effect of lncRNA DHRS4-AS1 on the growth of TC transplantation tumors. Results Dual luciferase reporter assays showed a targeting relationship between lncRNA DHRS4-AS1, miR-221-3p, and SOCS3. LncRNA DHRS4-AS1 and SOCS3 were downregulated and miR-221-3p was upregulated in FTC-133 cells. Overexpression of lncRNA DHRS4-AS1 inhibited proliferation, migration, and invasion of FTC-133 cells, while inducing apoptosis. Conversely, miR-221-3p overexpression reversed these inhibitory effects, and suppressed the apoptosis. Nude mouse transplantation experiment observed that overexpression of lncRNA DHRS4-AS1 resulted in a decrease in tumor tissue quality and volume, and a decrease in miR-221-3p expression and an increase in SOCS3 expression. Conclusion LncRNA DHRS4-AS1 is downregulated in FTC-133 cells. Overexpression of lncRNA DHRS4-AS1 can inhibit the proliferation, invasion, and migration of TC cells and induce apoptosis by regulating the miR-221-3p/SOCS3 signaling axis.
MicroRNAs/metabolism* ; Suppressor of Cytokine Signaling 3 Protein/metabolism* ; Humans ; RNA, Long Noncoding/metabolism* ; Apoptosis/genetics* ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Thyroid Neoplasms/physiopathology* ; Animals ; Signal Transduction/genetics* ; Cell Line, Tumor ; Mice, Nude ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic ; Mice ; Mice, Inbred BALB C

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective:To explore the real experience and needs of lymphoma patients during chimeric antigen receptor T cell (CAR-T) therapy, so as to provide guidance for developing nursing intervention strategies.Methods:The phenomenological research method was used to conduct semi-structured interviews with 13 lymphoma patients receiving CAR-T therapy, and the interview data was analyzed using the Colaizzi 7-step analysis method.Results:Three themes were extracted, including diverse symptom perception (systemic symptoms such as fever and fatigue, as well as multiple system symptoms such as breathing, digestion, and nerves), complex emotional experience interweaving (coexistence of hope and doubt, changes and loss of environmental adaptability, and a variety of negative emotions), and urgent social needs (treatment related information needs, desire for medical and nursing staff's attention and help, family emotional support, and home rehabilitation continuing care) .Conclusions:Lymphoma patients experience significant physical and mental pain during CAR-T therapy. Medical and nursing staff should provide patients with comprehensive support to help them identify and improve physical discomfort symptoms, reduce psychological burden, meet physical and mental needs, and promote disease recovery.

Radix Bupleuri has been used in traditional Chinese medicine for over 2000 years with functions of relieving exterior syndrome,clearing heat,regulating liver-qi,and lifting yang-qi.Its medicinal properties have been widely used in Eurasia and North Africa.As the main bioactive compounds in Radix Bupleuri,saikosaponins(especially saikosaponin A and saikosaponin D)have anti-inflammatory,anti-tumor,antioxidant,antivirus,immune regulatory,and liver protective effects.This article reviews the pharmacological activity,mechanism of action,and current applica-tion status of saikosaponins,in order to provide new insights for further research and development of Radix Bupleuri.

OBJECTIVE To identify the role of mixed lineage kinase domain like protein(MLKL)in cerebral small vessel disease(CSVD)and explore the underlying mechanism.METHODS Transient bilateral common carotid artery occlusion(tBCCAO)was used to establish a mouse model of CSVD.Immunofluorescence staining and Western blotting were used to observe the expres-sions of RIPK3/MLKL signaling molecules in brain tissues at 7,14 and 28 d after tBCCAO.Open field test,rotarod test,Y-maze and novel object recognition test were used to observe the effect of MLKL knockout on cognitive func-tion after tBCCAO.Blood-brain barrier(BBB)disruption was observed by sodium fluorescein permeability test and the expressions of tight junction proteins.Immunoflu-orescence staining and Western blotting were used to detect the expression of microglia marker Iba-1,astro-cyte marker GFAP,and NLRP3/Caspase-1 signaling mol-ecules in the hippocampus of CSVD mice.ELISA was used to detect the level of inflammatory factors(TNF-α,IL-1β,IL-18)in hippocampus.RESULTS The expres-sions of RIPK3/MLKL signaling molecules increased in cortex and hippocampus after tBCCAO,especially on day 14.The expression of pMLKL mainly increased in neurons,glia cells and endothelial cells in CSVD mice.MLKL knockout improved the cognitive functions such as motor learning,spatial learning and working memory,and object recognition ability in CSVD mice.MLKL knock-out alleviated the leakage of sodium fluorescein and attenuated the down-regulation of tight junction proteins at 1 d and 14 d after tBCCAO.At 14 d after tBCCAO,MLKL knock out inhibited the activations of microglia and astrocytes,attenuated the expressions of NLRP3/cas-pase-1 molecules,and decreased the levels of inflamma-tory factors in the hippocampus of mice.CONCLUSION Genetic inhibition of MLKL exerts protective effects against cognitive impairment by ameliorating BBB dam-age and neuroinflammation in a mouse cerebral small vessel disease model.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Objective:To investigate the efficiency and safety of pneumatic retinopexy for rhegmatogenous retinal detachment (RRD).Methods:A prospective case series study. From January 2020 to December 2021, 27 eyes of 27 RRD patients in Joint Shantou International Eye Center were included. Among them, there were 10 males and 17 females; the mean age was 36.0±11.8 years old. There was recurrent retinal detachment in 4 eyes. Best corrected visual acuity (BCVA) and optical coherence tomography were performed. According to whether the retina was successfully reattached after a single intravitreal injection, the patients were divided into a single operation group and a second operation group. All eyes underwent pneumatic retinopexy, the patients received intravitreal injection of 0.3-0.5 ml 100% C 3F 8. On the next day, laser photocoagulation was performed around the retinal breaks. The mean follow-up time was 15.0±6.0 months. Outcome measures included single operation success rate, the BCVA at the last follow up and complications. The age, gender, extent of retinal detachment, number of retinal breaks, and preoperative and postoperative BCVA of patients in the single operation group and the second operation group were compared using Mann-Whiteney test or Fisher's exact test. Results:Twenty of the 27 eyes (74.1%, 20/27) had retinal reattachment after single operation, 7 of the 27 eyes (25.9%, 7/27) had retinal reattachment after the second operation. Among the 7 eyes, retinal detachment recurrence after operation, retinal detachment recurrence after tear opening, and retinal detachment recurrence with new tears occurred in 1, 4, and 2 eyes, respectively; retinas were all reattached after scleral buckling or vitrectomy. The BCVA was stable and improved in 14 and 13 eyes, respectively. Compared with the single operation group, the retinal detachment in the second operation group was wider and the BCVA before operation was worse, the differences were statistically significant ( Z=-2.842,-2.233; P<0.05). Transient intraocular pressure elevation occurred in 5 eyes; no complications such as infectious endophthalmitis, intraocular hemorrhage and lens damage occurred. Conclusion:Pneumatic retinopexy is safe and effective in the treatment of RRD.

Objective:There is currently no consensus on the ideal plane for implant placement in breast reconstruction. This meta-analysis provides a comparison of prepectoral breast reconstruction (PBR) vs. subpectoral breast reconstruction (SBR), with primary outcomes of surgical efficacy and patient safety, to find out the best surgical approach.Methods:PubMed, Cochrane, Web of Science, and Embase databases were searched from January 1st, 2019, to April 1st, 2022, to retrieve studies that compared PBR with SBR after mastectomies. The main outcomes were surgical complications and satisfaction with breasts domain. The literature was screened according to the inclusion and exclusion criteria, the data was extracted and the methodological quality of the included studies was assessed by 2 reviewers independently. Meta-analysis was performed using RevMan 5.3.Results:A total of 14 comparative studies with 2 355 patients were included. The meta-analysis showed no statistical differences in seroma, implant removal, flap necrosis, capsular contracture, and wound dehiscence between PBR and SBR groups. PBR patients demonstrated lower hematoma, animation deformity rates, and higher BREAST-Q scores compared to SBR groups.Conclusions:Surgical efficacy and patient safety are similar between PBR and SBR groups. PBR patients have lower hematoma, animation deformity rates and are more satisfied with breasts domain. Further well-designed multi-center prospective studies are required to increase the robustness of the findings.

Objective:There is currently no consensus on the ideal plane for implant placement in breast reconstruction. This meta-analysis provides a comparison of prepectoral breast reconstruction (PBR) vs. subpectoral breast reconstruction (SBR), with primary outcomes of surgical efficacy and patient safety, to find out the best surgical approach.Methods:PubMed, Cochrane, Web of Science, and Embase databases were searched from January 1st, 2019, to April 1st, 2022, to retrieve studies that compared PBR with SBR after mastectomies. The main outcomes were surgical complications and satisfaction with breasts domain. The literature was screened according to the inclusion and exclusion criteria, the data was extracted and the methodological quality of the included studies was assessed by 2 reviewers independently. Meta-analysis was performed using RevMan 5.3.Results:A total of 14 comparative studies with 2 355 patients were included. The meta-analysis showed no statistical differences in seroma, implant removal, flap necrosis, capsular contracture, and wound dehiscence between PBR and SBR groups. PBR patients demonstrated lower hematoma, animation deformity rates, and higher BREAST-Q scores compared to SBR groups.Conclusions:Surgical efficacy and patient safety are similar between PBR and SBR groups. PBR patients have lower hematoma, animation deformity rates and are more satisfied with breasts domain. Further well-designed multi-center prospective studies are required to increase the robustness of the findings.