Colorectal cancer （CRC） is one of the most common cancers， with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages， CRC lacks specific symptoms， and most patients are diagnosed at advanced stages， making it a major research focus in the field of gastrointestinal tumors. Currently， clinical CRC treatments face several common challenges， including high surgical risks， frequent metastasis and recurrence， drug resistance， and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine （TCM）， it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation， invasion， migration， and angiogenesis， and promote apoptosis and autophagy， thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects， including activating blood circulation to dispel blood stasis， unlocking meridians to relieve pain， clearing heat to calm irritability， and cooling blood to reduce abscesses. It contains a variety of chemical components， including diterpenoids， phenolic acids， flavonoids， polysaccharides， nitrogen-containing compounds， steroids， and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms， including cell cycle arrest， promotion of apoptosis， inhibition of cell invasion and migration， induction of autophagy， suppression of tumor angiogenesis， and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.

OBJECTIVE: To explore the genetic basis of a child with Chanarin-Dorfman syndrome (CDS) manifesting as ichthyosis. METHODS: A child who had presented at Henan Provincial People's Hospital in June 2023 was selected as study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and her parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. Relevant literature was searched in databases using key words "Chanarin-Dorfman syndrome" and "ABHD5 gene". The clinical manifestations and variant sites of previously reported cases were compiled and analyzed for correlations. This study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital [Ethics No.: (2019) Jun Shen No. (134)]. RESULTS: WES revealed that the child has harbored compound heterozygous variants of the ABHD5 gene, namely c.99_103del (p.H34*) in exon 2 and c.770C>G (p.P257R) in exon 5, which were inherited from her father and mother, respectively. Bioinformatic analysis suggested that both variants were pathogenic. Literature review indicated that the affected organs in CDS are ranked from most to least including liver, eyes, ears, nervous system, muscles, spleen, and kidneys. The c.594insC and c.594dupC variants are most common. CONCLUSION The identification of the two novel ABHD5 gene variants has enriched the mutation spectrum of CDS. c.594insC or c.594dupC are hotspot mutations of this disease, albeit with no definitive correlation between the genotype and phenotype.
Humans ; Female ; Ichthyosiform Erythroderma, Congenital/genetics* ; Lipid Metabolism, Inborn Errors/genetics* ; Phenotype ; 1-Acylglycerol-3-Phosphate O-Acyltransferase/genetics* ; Mutation ; Muscular Diseases/genetics* ; Exome Sequencing ; Child ; Male ; Child, Preschool

Stroke ranks as the third leading cause of death and the fourth leading cause of disability worldwide. Its high disability rate and prolonged recovery period not only severely impact patients' quality of life but also impose a significant burden on families and society. Primary prevention is the cornerstone of stroke control, as early intervention on risk factors can effectively reduce its incidence. Therefore, the development of predictive models for first-ever stroke risk holds substantial clinical value. In recent years, advancements in big data and artificial intelligence technologies have opened new avenues for stroke risk prediction. This article reviews the current research status of traditional methods and machine learning models in predicting first-ever stroke risk and outlines future development trends from three perspectives: First, emphasis should be placed on technological innovation by incorporating advanced algorithms such as deep learning and large models to further enhance the accuracy of predictive models. Second, there is a need to diversify data types and optimize model architectures to construct more comprehensive and precise predictive models. Lastly, particular attention should be given to the clinical validation of models in real-world settings. This not only enhances the robustness and generalizability of the models but also promotes physicians' understanding of predictive models, which is crucial for their application and dissemination.

In recent years, with the endless emergence of meibomian gland dysfunction(MGD)diagnostic equipment, rich treatment methods, and in-depth clinical and basic research on MGD at home and abroad, the understanding of MGD has entered a new stage. MGD-related dry eye is considered to be the main cause of lipid abnormal dry eye, and its occurrence and development is a chronic and multi-factorial pathological process. This article reviews the pathogenesis, imaging analysis and clinical treatment progress of MGD-related dry eye, in order to provide scientific evidence and ideas for clinical diagnosis and therapy of MGD-related dry eye.

Objective To explore the efficacy of endoscopic therapy for esophageal and gastric variceal bleeding(EGVB),investigate the risk factors for rebleeding within 1 year,and establish a predictive model accordingly.Methods A retrospective study was conducted using the clinical and follow-up data of 120 EGVB patients who underwent endoscopy at our hospital between January 2021 and December 2022.The efficacy of endoscopic therapy was analyzed,and the patients were divided into a bleeding group and a non-bleeding group based on whether rebleeding occurred within 1 year after treatment.The factors influencing rebleeding within 1 year after treatment were analyzed,and a predictive model was established using logistic regression analysis.The model's goodness of fit was evaluated using the Hosmer-Lemeshow test,and its clinical value was analyzed using the receiver operating characteristic(ROC)curve.Results The hemostasis success rate within 72 hours after endoscopic therapy was 100％in all 120 patients.Four weeks after endoscopic treatment,endoscopic reexamination showed that the complete and partial disappearance rate of varices was 75.83％(91/120),with rebleeding occurring in 10 cases(8.33％).There were 34 cases(28.33％)of cumulative rebleeding at 6 months and 63 cases(52.50％)at 1 year after endoscopic therapy.Nine patients(7.50％)died within 1 year after endoscopic therapy,all of whom were rebleeding cases.A total of 63 patients with rebleeding were included in the bleeding group,and 57 patients without rebleeding were included in the non-bleeding group.Serum sodium＜135 mmol/L(odds ratio[OR]=3.837,95％confidence interval[CI]:1.095-13.445),Child-Pugh grade C(OR=3.835,95％CI:1.137-12.935),esophageal varices degree G3(OR=5.113,95％CI:1.565-16.707),and main portal vein diameter＞12 mm(OR=5.964,95％CI:2.295-15.497)were identified as risk factors of rebleeding within 1 year after endoscopic therapy in EGVB patients(P＜0.05).The risk prediction model for rebleeding within 1 year after endoscopic therapy in EGVB patients was shown as P=1/{1+e[-(-3.815+1.345×serum sodium+1.344×Child-Pugh grade+1.786×main portal vein diameter+1.632×esophageal varices degree)]}.The Hosmer-Lemeshow x2 was 3.158(P=0.856).The area under the curve(AUC)for predicting rebleeding within 1 year after endoscopic therapy in EGVB patients was 0.815,indicating good predictive performance.Clinical validation showed that the model had an accuracy of 82.30％,with sensitivity and specificity being 81.03％and 83.63％,respectively.Conclusion Endoscopic therapy for EGVB achieves a high rate of acute bleeding control,but patients remain at risk of rebleeding.Rebleeding is associated with serum sodium＜135 mmol/L,Child-Pugh grade C,main portal vein diameter＞12 mm,and esophageal varices degree G3.The logistic regression model can effectively predict the probability of rebleeding within 1 year after endoscopic therapy.

Objective To investigate the effect of dexmedetomidine(DEX)on cognitive func-tion in rats with cerebral ischemic stroke(CIS)and analyze its potential underlying mechanisms.Methods A rat model of CIS was established using the middle cerebral artery occlusion(MCAO)method.The rats were randomly divided into sham-operation group,model group,low-dose DEX group(25 mg/kg DEX solution,administered by gavage),high-dose DEX group(50 mg/kg DEX solution,administered by gavage),and edaravone group(3.2 mg/kg edaravone solution,adminis-tered by gavage).After treatment,cognitive function was assessed using the neurological deficit score and the novel object recognition test.Brain infarction area and histopathological damage in brain tis-sue were detected using triphenyltetrazolium chloride(TTC)staining and hematoxylin and eosin(HE)staining,respectively.The expression of the microglial marker ionized calcium-binding adapter molecule 1(Iba-1)was analyzed using immunohistochemical staining.The levels of interleukin(IL)-6,IL-18,and IL-1β in brain tissue were measured using ELISA kits.The expression of proteins related to the toll-like receptor 4/nuclear factor KB/NOD-like receptor thermal protein do-main-containing protein 3(TLR4/NF-κB/NLRP3)signaling pathway was detected using western blot.Results Compared with the sham-operation group,the model group exhibited increased or enlarged neurological scores,brain infarction area,levels of IL-6,IL-1β,IL-18,Iba-1,TLR4,p-NF-κB,NLRP3,Cleaved Caspase-1,and GSDMD-N,as well as a decreased novel object discrimination in-dex.Compared with the model group,the low-dose DEX,high-dose DEX,and edaravone groups showed decreased or shrinked neurological scores,brain infarction area,levels of IL-6,IL-1β,IL-18,Iba-1,TLR4,p-NF-κB,NLRP3,Cleaved Caspase-1,and GSDMD-N,along with an increased novel object discrimination index.Compared with the low-dose DEX and edaravone groups,the high-dose DEX group demonstrated further decreases in neurological scores,brain in-farction area,levels of IL-6,IL-1β,IL-18,Iba-1,TLR4,p-NF-κB,NLRP3,Cleaved Caspase-1,and GSDMD-N-terminal domain(GSDMD-N),as well as an increased novel object discrimination index.The differences among the aforementioned groups were all statistically significant(P＜0.05).Conclusion DEX improves cognitive function in rats with CIS by inhibiting the activation of the TLR4/NF-κB/NLRP3 signaling pathway,thereby suppressing neuronal pyroptosis and micro-glial activation and alleviating the inflammatory response.

A 48-year-old woman was treated with toripalimab for triple negative breast cancer.She developed symptoms of pollakiuria and urinary urgency after 1st cycle of toripalimab,and was hospitalized for severe abdominal pain after 2nd circle of treatment,after symptomatic treatment,the condition improved.However,after the 3rd,4th,and 5th cycles of medication,the symptoms recurred.The symptoms did not reappear after discontinuing toripalimab.Therefore,ureteritis associated with immune checkpoint inhibitors(ICI)was considered based on case characteristics,urine routine,urine culture,ultrasound and CT findings.According to Naranjo's Assessment Scale,the association between toripalimab and ureteritis was considered"definite".The possibility of ureteritis associated with ICI should be considered if symptoms of urinary tract irritation occur during the use of toripalimab,and urine analysis,urine culture,and imaging examination should be conducted to detect such adverse reactions earlier.

Objective:To investigate clinical characteristics and genetic variations in a case of self-improving collodion ichthyosis in the adult stage.Methods:An adult patient with clinically suspected self-improving collodion ichthyosis was collected from the Department of Dermatology, Henan Provincial People′s Hospital in April 2023. Clinical data were collected from the patient and her parents. Peripheral blood samples were obtained from them, and whole blood DNA was extracted. Whole-exome sequencing was performed to screen genetic variation sites, which were then verified by Sanger sequencing. The deleteriousness of the identified variants was assessed using pathogenicity analysis software.Results:The 54-year-old female patient presented with facial and neck flushing, mild dry skin on the trunk and limbs, sheepskin-like skin of the dorsal hand, and short fingers. Genetic testing identified two in-frame deletion mutations c.406_408del (p.E136del) and c.769_801del (p.H257_Q267del) in the non-repetitive region of the ALOX12B gene in the patient, which were inherited from her father and mother respectively. Bioinformatics analysis revealed that both genetic variations were deleterious pathogenic mutations.Conclusions:Two in-frame deletion mutations c.406_408del (p.E136del) and c.769_801del (p.H257_Q267del) were identified in the non-repetitive region of the ALOX12B gene in the patient with self-improving collodion ichthyosis, which may contribute to the clinical phenotype of the patient. The mutation c.769_801del had not been reported in literature.

To report 3 cases of acute generalized exanthematous pustulosis (AGEP) caused by hydroxychloroquine. All the 3 patients were females, aged 23, 30, and 28 years respectively. In cases 1 and 3, the rashes appeared 4 days and 12 days respectively after the treatment with hydroxychloroquine for systemic lupus erythematosus; case 2, who was 8 weeks pregnant, developed rashes 10 days after starting hydroxychloroquine treatment for antiphospholipid syndrome. All the 3 patients had high fever, and clinically presented with generalized round or oval-shaped edematous erythema on the face, neck, trunk and limbs, covered with a large number of pinhead-sized pustules, and with multiple erythema multiforme-like lesions on the trunk and both upper limbs, including targetoid lesions. Mutations in the IL36RN gene were identified in all the 3 patients: a homozygous mutation c.115+6T>C in the IL36RN gene was found in case 1, and her parents were heterozygous carriers; case 2 inherited the heterozygous mutation c.115+6T>C in the IL36RN gene from her mother; the heterozygous mutation c.115+6T>C found in case 3 was a de novo mutation. A diagnosis of AGEP was made in all the 3 cases. Cases 1 and 2 received subcutaneous injections of adalimumab in addition to the treatment of their underlying diseases, and skin lesions markedly regressed after 1 week of treatment; case 3 was treated with high-dose glucocorticoids, and lesions subsided after 4 weeks; no significant adverse reactions were observed in cases 1 and 2, however, femoral head necrosis was noted in case 3. During a follow-up period of 42 months, none of the patients experienced recurrence, and case 2 gave birth to a healthy baby boy after 8-month treatment.

Objective:To analyze the genetic characteristics of the prevalent strains of Varicella-Zoster virus (VZV) in the population of Dali, Yunnan, and to understand its evolutionary status in the population of Dali.Methods:Herpes fluid and 163 sera were collected from 249 patients clinically suspected to have varicella or herpes zoster in the Department of Dermatology of the Second People′s Hospital of Dali city, Yunnan province, China, from 2023 to 2024. The levels of VZV-specific IgG and IgM antibodies in serum were detected using enzyme-linked immunoassay. Viral DNA was extracted from the herpes fluid, and the cycle threshold ( Ct) of the samples was detected using quantitative real-time polymerase chain reaction (qPCR), and some samples with Ct ≦ 22 were selected for sequencing by next-generation sequencing technology (next-generation sequencing). Next-generation sequencing (NGS) was used to obtain 90 whole genome sequences of VZV, and the sequencing result were compared with the sequences of reference strains for multiple sequence comparison and evolutionary analysis. Snapgene was used to translate the nucleotides into amino acids, and the result were compared with the amino acid sequences of the reference strain. Results:Of the 90 VZV whole-genome sequences, one whole-genome sequence was from an adult varicella patient, and the remaining 89 whole-genome sequences were from herpes zoster patients. The serum-specific IgG antibody positivity rate was 99.4%, and the IgM antibody positivity rate was 52.8%. The result of both single nucleotide polymorphism (SNPs) site typing and genome-wide phylogenetic tree analysis showed that 83 of the 90 VZV whole-genome sequences in this study were on the same branch as Clade 2, and 7 VZV whole-genome sequences were on the branch of Clade 9.Conclusions:The main endemic branch in Dali region in 2023-2024 was Clade 2, with the emergence of Clade 9 branch; there were amino acid mutations in the proteins encoded by ORF22 and ORF68 in 83 VZV whole genome sequences of Clade 2 branch, and the mutations did not cause significant changes to the protein structure.