Cancer is a major global health issue. Effective therapeutic strategies can prolong patients’ survival and reduce the costs of treatment. Drug repurposing, which identifies new therapeutic uses for approved drugs, is a promising approach with the advantages of reducing research costs, shortening development time, and increasing efficiency and safety. Disulfiram (DSF), a Food and Drug Administration (FDA)-approved drug used to treat chronic alcoholism, has a great potential as an anticancer drug by targeting diverse human malignancies. Several studies show the antitumor effects of DSF, particularly the combination of DSF and copper (DSF/Cu), on a wide range of cancers such as glioblastoma (GBM), breast cancer, liver cancer, pancreatic cancer, and melanoma. In this review, we summarize the antitumor mechanisms of DSF/Cu, including induction of intracellular reactive oxygen species (ROS) and various cell death signaling pathways, and inhibition of proteasome activity, as well as inhibition of nuclear factor-kappa B (NF-κB) signaling. Furthermore, we highlight the ability of DSF/Cu to target cancer stem cells (CSCs), which provides a new approach to prevent tumor recurrence and metastasis. Strikingly, DSF/Cu inhibits several molecular targets associated with drug resistance, and therefore it is becoming a novel option to increase the sensitivity of chemo-resistant and radio-resistant patients. Studies of DSF/Cu may shed light on its improved application to clinical tumor treatment.

Objective:To compare the differences in surgical safety and postoperative cosmetic effects between endoscopic nipple-sparing mastectomy with immediate prepectoral prosthesis breast reconstruction and conventional nipple-sparing mastectomy with immediate subpectoral prosthesis breast reconstruction.Methods:The clinical data of early breast cancer patients admitted to the Department of Breast Surgery of Peking University Peoples Hospital from Oct 1, 2022 to Sep 13, 2023 was retrospectively analyzed.Results:According to the surgical method, the patients were divided into endoscopic surgery group (30 cases) and traditional surgery group (46 cases). There were no significant differences in the basic clinicopathological data, and the number of sentinel lymph nodes taken and axillary lymph nodes dissected between the patients in two groups (all P>0.05). Compared with that in traditional surgery group, the patients in endoscopic surgery group had longer operation time and more wound drainage volumes 3 days after surgery (all P<0.05). There was no significant differences in the probability of postoperative complications between the patients in two groups (all P>0.05), however, the proportion of nipple-areola complex necrosis in patients of endoscopic surgery group (10.0%) was lower than that of traditional surgery group (26.1%). Conclusions:The single-port insufflation technique-assisted endoscopic nipple-sparing mastectomy with immediate prepectoral prosthesis breast reconstruction maximize the cosmetic effect. Under the premise of strict selection of indications, it can be an optional surgical method.

Objective:To analyze the gene mutation type and clinical phenotype of patients with PRRT2 mutation, and explore their relations with prognosis. Methods:A total of 18 patients with PRRT2 gene mutation (1 patient with novel mutation in PRRT2 gene, and 17 probands in 17 families with PRRT2 gene mutation) were enrolled in Department of Neurology, First Affiliated Hospital of Air Force Medical University from January 2018 to July 2023. Serum of the patients was collected for whole exon sequencing, and mutation sites and types of PRRT2 gene were analyzed. SWISS-MODEL website was used to predict the changes in protein structure caused by PRRT2 gene mutation. The relations of gene mutation type and clinical phenotype with prognosis of these patients were analyzed. Results:(1) All 18 patients with PRRT2 gene mutation were heterozygous mutation, including 12 frameshift mutations, 5 missense mutations, and 1 integer mutation. The clinical phenotype included benign familial infantile epilepsy (BFIE) in 5 patients, epilepsy in 6 patients, exercise-induced paroxysmal kinesigenic dyskinesia (PKD) in 5 patients, and infantile convulsion and choreoathetosis (ICCA) in 2 patients. A total of 8 mutation sites were found in 18 patients with PRRT2 gene mutation, of which 3 mutation sites have been reported, and 5 mutation sites have not been reported, including c.647(exon2)C>A, c.647(exon2)C>G, c.170(exon2)delC, c.981(exon3)C>G, and lossl(EXON: 2)(all). (2) Eighteen patients mainly accepted oxcarbazepine, levetiracetam, and sodium valproate in combination or monotherapy. Among them, 5 BFIE patients, 2 ICCA patients and 3 epilepsy patients were seizure-free after treatment. PKD patients did not respond well to oxcarbazepine. (3) Three frameshift mutations (mutation sites: c.649 [exon2]_c.650 [exon2] insC, c.640 [exon2]_c.641 [exon2] insC, and c.170 [exon2] delC) led to premature termination of protein translation, resulting in significant changes in protein structure. Four missense mutations (mutation sites: c.640[exo2]G>C, c.647[exon2]C>A, c.647[exon2]C>G, and c.981[exon3]C>G) had little effect on protein structure changes. No relation was found between changes of protein structure caused by different mutation types and prognosis. Conclusion:PRRT2 gene mutation patients with clinical phenotypes of BFIE and ICCA have good prognosis, but the mutation type is not related with the prognosis of patients.

Objective To retrieve,evaluate and summarize the relevant evidence on malnutrition management among maintenance hemodialysis(MHD)patients to provide clinical medical staff with evidence-based guidelines for managing malnutrition in MHD patients.Methods Using the"6S"pyramid model of evidence,We searched UpToDate,BMJ best clinical practice,the Australian JBI evidence-based health care centre database(JBI),Medive,the International Guidelines Collaborative Network(GIN),Agency for Healthcare Research and Quality Network,the UK National Institute of Clinical Medicine Guidance Library(NICE),Scottish Inter-College Guide Collaboration network,the Ontario Registered Nurses Association(RNAO),Guidelines Network of International Society of Nephrology,American Nephrology Foundation Guidenet,British Nephrology Society,Society of Nephrology,Chinese Medical Association,Improving Kidney Disease Outcomes Worldwide,International Society of Renal Nutrition and Metabolism,American Society for Parenteral Enteral Nutrition,European Society for Clinical Nutrition and Metabolism,Chinese Nutrition Society,PubMed,Web of Science,Embase,Cochrane Library,CNKI,Wanfang,VIP and CBM,to collect relevant guidelines,expert consensus,clinical decision,evidence summary,recommended practice,best practice,systematic evaluation and clinical practice,from the establishment to the date of April 10th,2023,for literature on malnutrition management of MHD patients.The literature included guidelines,expert consensuses,clinical decision-making studies,evidence summaries,recommended practices,best practices,and systematic reviews.Two researchers independently evaluated,extracted,and integrated the evidence.The evidence was graded by the evidence pre-grading system of the Evidence-based Healthcare Center of Joanna Briggs Institute(JBI).Results A total of 16 articles were included and summarized,comprising 5 guidelines,3 expert consensuses,1 clinical decision-making study,1 evidence summary,and 6 systematic reviews.Thirty-nine pieces of the best evidence were integrated,covering 5 key aspects(39 evidences):screening and assessment,nutritional requirements,nutritional supplement,other interventions,and monitoring and education.Conclusions The best evidence summary of malnutrition management among MHD patients in this study is scientifically rigorous and systematic.Clinical medical staff can use the best evidence to develop personalized malnutrition management programs for MHD patients.

Circular RNA has the advantages of a simple synthesis method,high stability,and continuous and stable expression over linear mRNA,and has great potential for application in microbial infection vaccines,tumor vac-cines,protein replacement therapy,etc.In recent years,circular RNA has become a hotspot in the field of nucleic acid drugs.The cyclization technique of RNA is the key to the synthesis of circular RNA in vitro.The cyclization strategy has an important impact on cyclization efficiency,immunogenicity,protein expression,etc.,which limits the basic research and clinical application of circular RNA.This paper provides a systematic review of several cyclization strategies including the chemical method,enzyme method,and ribozyme method.The reaction conditions,cyclization process,cyclization ef-ficiency,and immunogenicity of each cyclization technology were analyzed.At present,the ideal circular RNA formation strategy still faces many challenges.However,studies have confirmed that circular RNA has better stability and stronger immune effects than linear mRNA in the fields of coronavirus disease 2019(COVID-19)vaccine and anti-tumor vaccine.Consequently,circular RNA has become a novel nucleic acid drug molecule with great potential.This research provides valuable insights for optimizing and expanding the research and clinical application of circular RNA.

Rheumatoid arthritis （RA） is a systemic autoimmune disease with local joint pain as the main clinical manifestation. It is one of the diseases specifically responding to traditional Chinese medicine （TCM）. The occurrence of RA is not only related to innate factors like genetic disorder but also associated with environmental factors， such as diets and microbial infection. The intestine， a vital human organ with digestive and immune functions， is a place where microorganisms colonize and exert intestinal metabolism-improving， barrier-protecting， and immunomodulatory effects. As the research on the onset and treatment of RA is deepening， the potential relationship of intestinal structural and functional abnormalities with the pathogenesis and progression of RA has been revealed. As clinical and experimental studies indicated， joint inflammation coexists with the impaired barrier function， imbalanced immune cells， and disordered gut microbiota. The theory of the gut-joint axis in the pathogenesis， progression， and treatment of RA is highly consistent with the holistic view in TCM. The recent pharmacological studies have shown that Chinese medicine prescriptions and active components can inhibit inflammation， protect joints， and maintain the intestinal function. This article summarizes the basic connotation of the gut-joint axis in RA and the mechanism by which TCM protect the intestinal barrier and modulate the immunity by regulating the gut microbiota structure and improving microbial metabolism in the treatment of RA. This review gives insights into the future research on the gut-joint axis in RA.

Perimenopausal syndrome （MPS）， a common endocrine system disease， is one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in endocrinology， gynecology， and interdisciplinary fields of both Western and Chinese medicine to discuss the advantages and challenges of diagnosing and treating MPS with Western medicine， TCM， and integrative medicine. Experts at the conference believe that MPS is initiated by estrogen decline and rooted in deficiency， with the pathogenesis being imbalance between Yin and Yang in the kidney. The hormone replacement therapy in Western medicine for menopause can rapidly alleviate related symptoms by quickly restoring the estrogen level and timely detect and delay complications of menopause， whereas such a therapy has certain risks， necessitating close monitoring of adverse reactions. Moreover， the various contraindications and precautions limit the clinical application of the hormone replacement therapy. TCM has advantages in synergistically alleviating symptoms such as hot flashes， sweating， sleep disorders， and emotional abnormalities of MPS without causing obvious adverse reactions. However， its efficacy is slower than the hormone replacement therapy， and the TCM evidence for preventing and treating complications of menopause remains unclear. Three suggestions were proposed for the future development of both Western and TCM for ameliorating MPS. First， an integrated diagnosis and treatment system for MPS with both Western and Chinese medicine should be established. Second， high-quality evidence-based interventions for MPS should be developed with TCM alone or in combination with Western medicine. Third， efforts should be made to promote the new TCM drug development and the interdisciplinary cooperation for treating MPS.

Background and objective The proportion of patients carrying driver gene mutations is notably high among individuals with non-small cell lung cancer(NSCLC)in China.However,the current neoadjuvant treatment strategies for these patients lack evident benefits.This study aims to investigate the efficacy and adverse reactions of neoadjuvant immu-nochemotherapy in patients with driver gene-positive NSCLC,thereby exploring its potential therapeutic value.Methods A total of 50 patients from two centers were retrospectively collected to compare the efficacy and adverse reactions among driver gene-positive NSCLC patients after different treatments and further explore the response to neoadjuvant immunochemo-therapy among different EGFR-sensitive subtypes.Results A total of 50 patients from two centers were included in this study.Among the 40 patients from Peking University People's Hospital(PKUPH),21 received neoadjuvant immunotherapy,with 57.1％ showing partial response on imaging.The major pathological response(MPR)rate after neoadjuvant immunochemo-therapy was 38.1％ ,and pathological complete response(pCR)was only observed in this group.No significant differences were noted in adverse events or their impact on surgical difficulty among different treatments.Additionally,10 patients from Hunan Cancer Hospital(HNCA)were included to analyze the differences in efficiency among EGFR-sensitive subtypes under various neoadjuvant strategies.No significant radiological response differences were observed between neoadjuvant immunotherapy and targeted therapy.However,patients with the L858R mutation exhibited MPR and pCR only after receiving immuno-therapy,surpassing targeted therapy outcomes,while no significant differences were found among 19del patients.Conclusion Under the premise of not exacerbating adverse effects,neoadjuvant immunochemotherapy achieved superior rates of MPR and pCR,with long-term survival comparable to targeted therapy.

Objective:To evaluate the impact of orthopedic robotic assistance and conventional freehand methods on surgical strategies, the safety of pedicle screw placement, and clinical efficacy in patients with upper cervical spine diseases.Methods:From January 2017 to March 2023, a total of 63 cases with upper cervical spine disease, were divided into two groups based on the screw placement technique: the robot-assisted pedicle screw placement (RA) group (41 cases) and the conventional freehand pedicle screw placement (CF) group (22 cases), were retrospectively included. These patients in the RA and CF groups underwent two types of posterior cervical surgery, including occipitocervical fusion (9 cases and 8 cases) and fixation and fusion of atlantoaxial and distal vertebrae (32 cases and 14 cases). The outcome parameters, including the disease course, surgical time, intraoperative blood loss, fluoroscopy frequency, radiation dose, hospital stay, treatment costs, complications, the rate of the pedicle screw placement, accuracy of upper cervical pedicle screw placement, and the risk factors that possibly affected the accuracy were recorded and analyzed. Postoperative follow-up was conducted for at least 6 months, and the efficacy of patients was assessed using imaging parameters, ASIS classification, VAS, and JOA scores.Results:Both groups had no screw-related complications and no spinal cord or vertebral artery injuries. In the RA group, the pedicle screw placement rates for the patients with occipitocervical fusion, and fixation and fusion of atlantoaxial and distal vertebrae were 100% (48/48) and 89.6% (138/154), respectively, far exceeding the placement rate in the CF group 42.9% (18/42) and 78.3% (54/69) (χ 2=37.403, P<0.001; χ 2=5.128, P=0.024). The fluoroscopic exposure dose and operation time of the two types of surgical patients in the RA group were both higher than those in the CF group ( P<0.05). Compared with the CF group, the accuracy of C 1 screws in the RA group increased from 42% (11/26) to 80% (51/64), with statistical significance (χ 2=13.342, P=0.004); while the accuracy of C 2 screws improved from 77% (33/43) to 88% (63/72) with no statistical difference (χ 2=2.863, P=0.413). Non-parametric correlation analysis found a significant correlation between the accuracy of C 1 and C 2 pedicle screw placement and the order of guide wire insertion in the RA group ( r=0.580, P<0.001; r=0.369, P=0.001). Postoperatively, both groups showed significant differences in cervicomedullary angle (CMA), Chamberlain angle (CL), McGregor angle, Boogard angle, Bull angle, clivus-canal angle (CCA), occipitocervical (C 0-C 2) angle, posterior occipitocervical angle (POCA), C 2-C 7 angle, and anterior atlantodental interval (ADI) ( P<0.05). The ASIA classification improved to varying degrees for both groups postoperatively, but there were no statistically significant differences between preoperative, postoperative, and last follow-up evaluations. VAS and JOA scores significantly improved for both groups postoperatively and at the last follow-up ( P<0.05). Conclusion:Both orthopedic robotic-assisted and conventional freehand pedicle screw placement techniques achieved satisfactory therapeutic effects in the treatment of upper cervical spine diseases. The orthopedic robot can effectively ensure the accuracy of upper cervical pedicle screw placement, the increase placement rate of pedicle screws in the upper cervical spine, and reduce fluoroscopy exposure. However, it is necessary to avoid the vertebral displacement caused by the priority insertion of the guide needle, which may affect the accuracy of subsequent planning.

Objective: To identify the functional connectivity characteristics of insula, sensory and social related brain regions in boys with autism spectrum disorder(ASD), to explore the central nervous basis of sensory abnormality affecting core symptoms in boys with ASD. Methods: Resting state functional magnetic resonance imaging (rs fMRI) data were collected from 34 boys with ASD and 29 typical development boys (TD group). Based on functional connectivity analysis, the sensory related brain regions, insula, and social related brain regions were taken as regions of interest to calculate the functional connectivity (FC) level between the regions of interest, the differences between the two groups were compared and the results were corrected by FDR. The Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS) and Autism Spectrum Quotient-Children s Version (AQ-Child) were used to assess the core phenotypes of boys with ASD. Results: Compared with the TD group, the levels of FC between tactile brain regions and insula, olfactory brain regions and insula, auditory brain regions and insula in boys with ASD group were significantly increased. The level of FC between the insula and bilateral amygdala，insula and the medial prefrontal cortex(mPFC) were significantly increased( P <0.05).Pearson correlation analysis showed that the level of FC between auditory brain region(BA42)and left insula in ASD group was negatively correlated with the scores of communication subscale of ADOS( r =-0.44)，social interaction subscale of ADOS( r =-0.43), communication & social interaction subscale of ADOS( r =-0.49),attention to details subscale of AQ-Child( r =-0.41). The level of FC between the right insula and right amygdala was positively correlated with the attention switch subscale of AQ-Child( r =0.38), the level of FC between right insula and mPFC was positively correlated with the scores of repetitive behavior subscale of ADOS( r =0.48), the attention switch subscale of AQ-Child( r =0.49), total scale subscale of AQ-Child( r =0.41), total scale of CARS( r =0.41)( P < 0.05 ). Conclusion The levels of FC between insula and sensory related, social related brain regions are abnormal in children with ASD, which have significant correlations with clinical symptoms. In depth studies can be conducted to explore underlying neutral mechanisms.