Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

Objective To systematically evaluate the therapeutic effects of video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracic surgery (RATS) in treating mediastinal tumors. Methods A computer search was conducted on PubMed, Embase, Cochrane Library, Web of Science, Wanfang, CNKI, CBM, VIP databases for literature comparing the clinical efficacy of VATS and RATS in treating mediastinal tumors, with the search time from inception to March 31, 2024. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included cohort studies, and Review Manager 5.4 software was used to perform a meta-analysis. Results A total of 32 articles were included, with 7868 patients. The NOS scores of the included cohort studies were all≥7 points. Meta-analysis results showed that compared with the VATS group, the RATS group had less intraoperative blood loss [MD=−16.71, 95%CI (−23.88, −9.54), P<0.001], lower conversion rate to open thoracotomy [OR=0.41, 95%CI (0.26, 0.67), P=0.003], lower overall postoperative complication rate [OR=0.66, 95%CI (0.48, 0.92), P=0.01], shorter postoperative drainage time [MD=−0.64, 95%CI (−0.92, −0.36), P<0.001], and shorter postoperative hospital stay [MD=−1.03, 95%CI (−1.28, −0.78), P<0.001]. There was no statistical difference between the two groups in terms of tumor size [MD=−0.06, 95%CI (−0.31, 0.19), P=0.64] or operation time [MD=5.52, 95%CI (−2.35, 13.40), P=0.17]. The RATS group had higher hospitalization costs than the VATS group [MD=1.69, 95%CI (1.26, 2.13), P<0.001]. Conclusion In mediastinal tumors resection, RATS is superior to VATS in terms of intraoperative blood loss, conversion rate to open thoracotomy, overall postoperative complication rate, postoperative drainage time, and postoperative hospital stay, but it increases hospitalization costs.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

To investigate the effectiveness of a self-developed intelligent medical record writing assistant in enhancing the efficiency of discharge record writing and improving the quality of discharge records, and to assess physicians' satisfaction with the assistant.

This paper conducts a pooled analysis of information related to orphan drugs approved for marketing in 2024 by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan. It systematically sorts out the scope of indications, therapeutic area distribution, and special review and approval pathways of these drugs, as well as their research and development progress and marketing status in China, thus providing a reference for researchers, regulatory authorities, and industry stakeholders in the field of rare disease drugs.

Ketamine is a dissociative anesthetic.It is clinically used as a surgical anesthetic or anes-thetic inducer and has a certain degree of mental dependence.Its abuse can lead to nerve damage,ad-verse emotional reactions and other toxic side effects.The primary mechanism by which ketamine exerts its pharmacological effects is to block N-methyl-D-aspartate receptors(NMDAR).It also functions through pathways such as α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid receptors(AMPAR),opioid receptors,γ-aminobutyric acid(GABA)receptors,monoaminergic receptors,cholinergic recep-tors,hyperpolarization-activated cyclic nucleotide-gated(HCN)channels,voltage-gated sodium channels,and L-type voltage-dependent calcium channels(VDCC).This article summarizes the molecular mecha-nism and toxic effects of ketamine's pharmacological functions,in order to provide a basis for foren-sic applications such as the identification of symptomatic phenotypes of ketamine toxic effects and the identification of ketamine abuse.

Objective To investigate the expression of E6-associated protein(E6AP)and BRG1-associated factor 155(BAF155)in patients with hepatitis B virus-related hepatocellular carcinoma(HBV-HCC)and its clinical prognostic significance.Methods A total of 126 patients with HBV-HCC diagnosed and treated in the First Affiliated Hospital of Harbin Medical University from January 2019 to February 2021 were retrospec-tively collected as the research subjects.The expressions of E6AP and BAF155 in cancer tissues and adjacent tissues of HBV-HCC patients were detected by real-time fluorescence quantitative PCR and immunohisto-chemistry.To analyze the relationship between the levels of E6AP mRNA and BAF155 mRNA and the clini-copathological characteristics of patients with HBV-HCC.The survival curve was plotted using the Kaplan-Meier method to analyze the effects of E6AP mRNA and BAF155 mRNA levels on the survival prognosis of patients with HBV-HCC.COX regression analysis was conducted to analyze the factors influencing the surviv-al prognosis of patients with HBV-HCC.Results Compared with adjacent tissues,the positive rates of E6AP mRNA and protein in cancer tissues of HBV-HCC patients were lower,while the positive rates of BAF155 mRNA and protein were higher,and the differences were statistically significant(P<0.05).Compared with the stage I of the China Liver Cancer Staging(CNLC),the maximum tumor diameter<5 cm and HBV-DNA negative,the E6AP mRNA was lower and the BAF155 mRNA was higher in the HBV-HCC cancer tissues of the CNLC stage Ⅱ—Ⅲ,the maximum tumor diameter≥5 cm and the HBV-DNA positive,the difference was statistically significant(P<0.05).The 3-year survival rates of the high-expression group and the low-expres-sion group of E6AP mRNA were 67.19%(43/64)and 38.71%(24/62),respectively,and the difference was statistically significant(Log rank χ2=10.540,P=0.001).The 3-year survival rates of the high-expression group and the low-expression group of BAF155 mRNA were 42.62%(26/61)and 63.08%(41/65),respec-tively,and the difference was statistically significant(Log rank χ2=6.876,P=0.009).The results of multi-variate COX analysis showed that CNLC stage Ⅱ—Ⅲ and BAF155 mRNA were risk factors affecting the prognosis of HBV-HCC,while E6AP mRNA was a protective factor.Conclusion The expression of E6AP is down-regulated and the expression of BAF155 is up-regulated in patients with HBV-HCC.Detecting the ex-pressions of E6AP and BAF155 is helpful for evaluating the prognosis of patients with HBV-HCC.

Objective:To explore the application effect of fine skin care in patients with psoriasis, and provide evidence-based theoretical basis for the development of skin care in patients with psoriasis.Methods:A randomized controlled trial was conducted. Patients with psoriasis admitted to the People′s Hospital of Wenshan Zhuang and Miao Autonomous Prefecture, Yunnan Province from December 2022 to March 2024 were selected as the research subjects by the convenience sampling method and divided into the control group and the experimental group by the random number table method. The control group was given routine care. The experimental group was given fine skin care on the basis of control group. Before and after the intervention, the itching symptoms, skin lesions, comfort and quality of life were evaluated using 12-item Pruritus Severity Scale (12-PSS), Psoriasis Area and Severity Index (PASI), General Comfort Questionnaire (GCQ), 36-item Short Form (SF-36) and compared between the two groups. The incidence of complications and recurrence rate in the two groups were counted 3 months after intervention.Results:Finally, 96 patients were included in the study, including 48 patients in the experimental group, 28 males and 20 females, aged (59.31 ± 17.31) years old; 48 cases in the control group, 29 males and 19 females, aged (61.54 ± 18.11) years old. Before the intervention, there were no statistically significant differences in the scores of 12-PSS, PASI, GCQ and SF-36 between the two groups (all P>0.05). After the intervention, the scores of 12-PSS and PASI in the experimental group were (3.65 ± 2.96), (5.08 ± 1.15) points respectively, which were lower than (8.29 ± 2.00), (7.37 ± 1.34) points in the control group, the differences were statistically significant ( t=9.00, 8.99, both P<0.05). The scores of GCQ and SF-36 in the experimental group were (41.42 ± 4.01), (95.08 ± 4.47) points respectively, which were higher than (33.94 ± 5.74) and (84.19 ± 8.52) points in the control group, the differences were statistically significant ( t=7.40, 7.84, both P<0.05). The total incidence of complications and recurrence rate in the experimental group were 4.17% (2/48), 2.08% (1/48) respectively, which were lower than 18.75% (9/48), 14.58% (7/48) in the control group, the differences were statistically significant ( χ2=5.03, 4.91, both P<0.05). Conclusions:Fine skin care can improve the itching symptoms of patients with psoriasis and reduce the severity of skin lesions. It can also improve the comfort and quality of life of patients and reduce the incidence of complications and recurrence rate, and the clinical application effect is good.

Prescription sequence symmetry analysis (PSSA) is one of the important methods for post-marketing pharmacovigilance based on the real-world medical prescription databases. It can be used to detect prescription cascades and mine adverse drug reaction (ADR) signals, which has been verified by many studies. PSSA shows high specificity and medium sensitivity in identifying ADR. It can quantify the correlation or risks of ADR. It is easy to use and simple in algorithm, and it has good robustness to some non time-dependent confounding factors. However, the results may be affected by some human confounding factors and data quality. This paper reviews the principle, calculation method, application scope, and precaution of PSSA by reviewing related literature on PSSA domestically and abroad, in order to provide reference for pharmacovigilance in China.

Objective:To understand the application situation and role of prescription sequence symmetry analysis (PSSA) in pharmacovigilance.Methods:The relevant databases at home and abroad were searched (up to April 30, 2024), and the original articles using PSSA as the research method were collected. The basic information of the literature (first author, publication year, country, etc.), the purpose and main content of the study, the index drugs as well as the marker drugs or medical diagnoses involved in the adverse drug reactions (ADRs) were extracted. Descriptive statistical analysis was carried out.Results:A total of 66 articles were included in the analysis. The first article was published in 1996, the number of articles published in recent years has increased significantly, and those published after 2016 accounted for 68.2% (45/66). The top 3 countries in terms of published literature quantity were the United States, Denmark, and Japan. The index drugs most commonly studied were those for the cardiovascular system and the neuropsychiatric system, in 18 and 14 articles respectively. The drugs studied in 3 or more papers were hypolipidemic drugs, antihypertensive drugs, antipsychotics, antiepileptics, proton pump inhibitors, hypoglycemic drugs and anticoagulants. The targeted ADRs/diseases most studied were those about the neuropsychiatric system (in 13 studies), followed by those about the endocrine and metabolic system (in 12 studies). The research objective in 47 articles was to explore the association between index drugs and ADRs/diseases through PSSA. Finally, the associations between 21 ADRs and index drugs were identified in 24 articles, of which 9 were new ADRs not recorded in drug instructions; benefits or potential preventive and therapeutic effects of index drugs on certain diseases were found in 7 studies. Ten studies were conducted to explore ADR information of specific drugs or detect suspicious drugs that cause specific ADRs, and some correlation signals between drugs and ADRs that previously unknown were detected. Nine studies evaluated the prescribing cascades, including the use of antitussive drugs after ACEI, the prescribing cascades related to drug-induced lower urinary tract symptoms and edema, the prescription cascades of statins, and the prescribing cascade relic.Conclusion:PSSA is a useful method for identifying potential prescribing cascades and mining ADR signals using medical prescription databases, especially suitable for the safety monitoring of long-term medication for chronic diseases and the signal detection of ADR that causal relationships are difficult to determine.