Objective To discuss the efficacy of transcatheter arterial chemoembolization(TACE)in combination with targeted therapy and immune checkpoint inhibitors for advanced hepatocellular carcinoma(HCC),and to identify the influencing factors.Methods A total of 60 patients with advanced HCC,who were admitted to the Air Force Medical Center of China from January 2016 to December 2022,were enrolled in this study.Thirty patients received TACE combined with targeted therapy and immune checkpoint inhibitors(TACE-L-P group),and the other 30 patients received TACE combined with targeted therapy(TACE-L group).The progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and objective response rate(ORR)were compared between the two groups.Results In the TACE-L group and TACE-L-P group,the median PFS(mPFS)was 7 months and 10 months respectively(P=0.011),the median OS(mOS)was 15.5 months and 29 months respectively(P=0.014).Child-Pugh class B(HR=3.89,95％CI:1.27-11.94,P=0.018)and Barcelona Clinic Liver Cancer(BCLC)stage C(HR=2.83,95％CI:1.32-6.03,P=0.007)were the independent risk factors for OS,while micro wave ablation(HR=0.21,95％CI:0.07-0.63,P=0.005)and TACE-L-P(HR=0.09,95％CI:0.03-0.3,P=0.001)were the independent protection factors for OS.Besides,elevated bilirubin level(HR=1.03,95％CI:1-1.06,P=0.032)and elevated gamma-glutamyl transferase(GGT)level(HR=1.01,95％CI:1-1.01,P=0.002)were the independent risk factors for disease progression,and TACE-L-P(HR=0.27,95％CI:0.09-0.79,P=0.017)was the independent protection factor for disease progression.The ORR and DCR in TACE-L-P group were remarkably higher than those in TACE-L group,which were 43.4％vs 13.3％and 63.4％vs 23.3％respectively,the differences between the two groups were statistically significant(both P＜0.05).Conclusion In treating advanced HCC,TACE combined with targeted therapy and immune checkpoint inhibitors is superior to TACE combined with targeted therapy in therapeutic efficacy.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Oral-facial-digital syndrome type Ⅰ(OFDSⅠ). METHODS: A child with OFDSⅠ who received treatment at the Women and Children's Hospital Affiliated to Ningbo University in March 2023 was selected as the study subject. A retrospective research method was used to collect the clinical data of the child. Peripheral venous blood samples were collected from the child, her parents and sister. Genomic DNA was extracted, and whole exome sequencing (WES) was performed. Candidate variants were validated using Sanger sequencing for familial verification. According to the Standards and Guidelines for the Interpretation of Sequence Variants developed by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines"), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Ningbo University Affiliated Women and Children's Hospital (Ethic No.: EC 2024-063). RESULTS: The child was a prematurely born female with deformities of the oral cavity, fingers, and toes. She was admitted to the Neonatal Department of the Hospital where she was born due to shortness of breath 15 minutes after birth. The WES results indicated that the child has harbored a heterozygous c.710dup (p.Y238Vfs*2) frameshifting variant of the OFD1 gene. Sanger sequencing confirmed that neither of the child's parents nor her sister had carried the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+PS4_Moderate+PM2-Supporting+PM6_Supporting+PP4). CONCLUSION Children with OFDSⅠ have clinical features such as oral, finger, and toe deformities. The c.710dup (p.Y238Vfs*2) variant of the OFD1 gene probably underlay the OFDSⅠ in this child. Above result has enriched the mutational spectrum of the OFD1 gene.
Humans ; Female ; Orofaciodigital Syndromes/genetics* ; Exome Sequencing ; Retrospective Studies ; Mutation ; Child ; Proteins

Objective:To investigate the variations in infrared radiation at Taichong(LR3),Taixi(KI3),and control points before and after menstruation and to examine the infrared radiation patterns associated with Yuan-primordial points of Zang-Fu organs during the physiological menstrual cycle. Methods:Using a point infrared radiation spectrum detection system,we detected the infrared radiation spectra of Taichong(LR3),Taixi(KI3),and the control points located 1 cm away from the two points,in a range of 1.50-18.00 μm wavelengths during the premenstrual,menstrual,and postmenstrual phases in 32 healthy adult women.Subsequently,data mining and analysis were conducted. Results:Before,during,and after menstruation,the infrared spectral shapes of bilateral Taichong(LR3),Taixi(KI3),and their control points were generally consistent,with characteristic infrared spectral wavelengths located at 11.25 μm.Prior to menstruation,the total intensity of infrared radiation at the right Taixi(KI3)was significantly lower than that at the control point(P<0.05),and that at the left Taichong(LR3)was significantly lower than that at the control point(P<0.01).During and after menstruation,the total infrared radiation intensity at both Taixi(KI3)was significantly lower than that of the control point(P<0.05).The wavelength points exhibiting significant differences in the infrared radiation intensity between points and control points were concentrated at the primary peak of 7.50-14.25 μm and the secondary peak of 15.00-17.25 μm. Conclusion:During different menstrual phases,the infrared radiation spectra of Taichong(LR3)and Taixi(KI3)exhibited distinct point specificity,mainly evident in the infrared radiation intensity and wavelength.

Objective:To study the changes in serum small molecule metabolites after brucella infection in humans using untargeted metabolomics methods, and screening representative biomarkers. Methods:A total of 109 serum samples collected from January 2019 to December 2021 at the Brucellosis Clinic of the Baotou Center for Disease Control and Prevention were divided into acute phase group ( n = 40), chronic phase group ( n = 35) of brucellosis, and healthy group ( n = 34) based on clinical diagnosis. Ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry technology was used to test serum samples and screen for differential metabolites. Receiver operating characteristic curve was used to evaluate the predictive ability of differential metabolites for brucellosis. Enriched pathways were screened using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to identify metabolic pathways significantly affected. Results:A total of 17 differential metabolites were screened between the acute phase group and the healthy group, and 12 differential metabolites were screened between the chronic phase group and the healthy group. There were a total of 5 differential metabolites (oleamide, linoleamide, stearamide, palmitoleic acid, α-linolenic acid) statistically significant among the three groups ( F = 16.84, 17.52, 14.31, 13.01, 20.76, P < 0.05). KEGG pathway analysis showed that the differential metabolites in the acute phase group were enriched in metabolic pathways such as ether lipid metabolism, glycerophosphate metabolism, sphingolipid signal and sphingolipid metabolism. The differential metabolites in the chronic phase group were enriched in metabolic pathways such as glycerophosphate metabolism, ether lipid metabolism, protein digestion and absorption metabolism. Conclusion:Untargeted metabolomics methods can screen out serum small molecule metabolites that undergo changes after brucella infection in the human body, including oleamide, linoleamide, stearamide, palmitoleic acid, α-linolenic acid can serve as potential biomarkers to distinguish brucellosis patients from healthy people.

Early-stage diagnosis of liver cancer is challenging, with an overall poor prognosis. The tumor microenvironment of primary liver cancer is complex, exhibiting significant heterogeneity both interpersonally and intratumorally. Therefore, it is of paramount importance to dynamically analyze biological markers in the tumor microenvironment of primary liver cancer in vivo. In recent years, significant progress has been made in the imaging diagnosis and treatment of liver cancer with the development of molecular imaging. Molecular imaging techniques utilize specific nano-imaging probes to evaluate pathological changes of liver cancer at the molecular and cellular levels in real-time. These techniques enable precise imaging to reveal key molecular biomarkers involved in the occurrence and progression of liver cancer, exploring their associations with cancer progression and outcomes. This article focuses on molecular imaging, emphasizing the current research status and latest advancements in the field of liver cancer diagnosis and therapy using techniques such as CT, MRI, optical imaging, PET imaging, and multimodal imaging. It also identifies important future directions and significant challenges for further development.

Antimicrobial resistance has become a major public health issue of global concern. Conjugation is an important way for fast spreading drug-resistant plasmids, during which the type Ⅳ pili plays an important role. Type Ⅳ pili can adhere on the surfaces of host cell and other medium, facilitating formation of bacterial biofilms, bacterial aggregations and microcolonies, and is also a critical factor in liquid conjugation. PilV is an adhesin-type protein found on the tip of type Ⅳ pili encoded by plasmid R64, and can recognize the lipopolysaccharid (LPS) molecules that locate on bacterial membrane. The shufflon is a clustered inversion region that diversifies the PilV protein, which consequently affects the recipient recognition and conjugation frequency in liquid mating. The shufflon was firstly discovered on an IncI1 plasmid R64 and has been identified subsequently in plasmids IncI2, IncK and IncZ, as well as the pathogenicity island of Salmonella typhi. The shufflon consists of four segments including A, B, C, and D, and a specific recombination site named sfx. The shufflon is regulated by its downstream-located recombinase-encoding gene rci, and different rearrangements of the shufflon region in different plasmids were observed. Mobile colistin resistance gene mcr-1, which has attracted substantial attentions recently, is mainly located in IncI2 plasmid. The shufflon may be one of the contributors to fast spread of mcr-1. Herein, we reviewed the discovery, structure, function and prevalence of plasmid mediated shufflon, aiming to provide a theoretical basis on transmission mechanism and control strategy of drug-resistant plasmids.
Plasmids/genetics* ; Proteins/genetics* ; Bacteria/genetics* ; Recombinases ; Genes, Bacterial ; Anti-Bacterial Agents

Purpose: Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. Materials and Methods: Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. Results: At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. Conclusion Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Objective To investigate the rules of Traditional Chinese Medicine in the treatment of perimenopausal syndrome (PMS) and provide a theoretical basis for the clinical treatment of PMS. Methods The literature related to PMS were collected from China Knowledge Network (CNKI), Wanfang database and Weipu database in the past 20 years, the herbal compound prescriptions for the treatment of PMS were screened and a relevant database were established and analyzed by SPSS. Results The relevant literatures contains 184 Chinese medicine prescriptions/proprietary Chinese medicines, 122 flavors of traditional Chinese medicines, and the drug categories were mainly tonic drugs, antipyretic drugs, astringent drugs, and tranquilizers. The core single-flavor Chinese medicines were Baishao(Radix Paeoniae Alba), Shudihuang(Rehmannia glutinosa ), Danggui(Radix Angelicae Sinensis), Fuling (Indian Buead). The property and flavor covered sweet, bitter, cold, etc.; and the channel tropism belonged to the liver, kidneys, heart, lungs, spleen and meridians. The cluster analysis of high-frequency Traditional Chinese Medicine obtained two main combinations. Conclusion TCM treatment of PMS focused on replenishing qi, soothing the liver, nourishing the kidneys, nourishing blood and calming the heart, and then according to clinical compatibility with drugs such as soothing the nerves, clearing heat and removing dampness; most of its clinical treatment were Xiaoyaosan, Liuwei Dihuang pills, and Zhibo Rehmanniae decoction and other prescriptions which were added and subtracted.

Objective:To investigate the value of transperineal ultrasound assessment of levator hiatal antero-posterior (LHap) diameter changes in the diagnosis of pelvic floor dysfunction.Methods:The clinical data of 246 patients with suspected pelvic floor dysfunction who received treatment in Yuyao People's Hospital of Zhejiang Province from October 2020 to June 2021 were retrospectively analyzed. All these patients underwent clinical examination and modified Oxford score (MOS) evaluation. They were divided into observation group (low pelvic floor muscle contractility) and control group (normal pelvic floor muscle contractility) according to MOS. All patients were subjected to ultrasound examination and LHap diameter measurement under three conditions (at rest, pelvic floor muscle contraction, and maximal Valsalva maneuver). The percentage of shortening of LHap diameter (PDC%) and the percentage of elongation of LHap diameter (PIV%) were calculated. The differences of PDC% and PIV% were compared between the observation and control groups. The receiver operating curve was used to evaluate the values of PDC% and PIV% in the diagnosis of pelvic floor dysfunction.Results:Age, body mass index, the proportion of parturient women among included patients, and the proportion of patients who underwent vaginal delivery were significantly higher in the observation group than those in the control group (all P < 0.001). LHap diameters measured when patients were at rest, pelvic floor muscle contraction, and maximal Valsalva maneuver as well as PIV% in the observation group were (45.23 ± 5.74) mm], (37.71 ± 8.44) mm, (51.03 ± 7.41) mm and (11.42 ± 4.79)%, respectively, which were significantly higher than those in the control group [(41.78 ± 4.56) mm, (29.15 ± 4.64) mm, (44.28 ± 4.87) mm, (6.05 ± 2.13)%, t = -4.62, -8.29, -7.26, -9.36, all P < 0.001]. PDC% in the observation group was significantly lower than that in the control group [(17.52 ± 5.58)% vs. (32.19 ± 4.27)%, t = 20.39, P < 0.001]. MOS was positively correlated with PDC% ( r = 0.56, P < 0.001) and it was negatively correlated with PIV% ( r = -0.49, P < 0.001). Taking PDC% < 35.36% as the cut-off value, the area under the receiver operating curve was 0.85, the sensitivity, specificity and accuracy values were 66.40%, 97.38%, and 73.90%, respectively. Taking PIV% > 5.18% as the cut-off value, the area under the curve was 0.70, and the sensitivity, specificity and accuracy values were 71.45%, 57.90% and 68.15%, respectively. When PDC% and PIV% were used together, the area under the curve was 0.73 and the sensitivity, specificity and accuracy values were 84.57%, 55.05% and 77.32%, respectively. Conclusion:Transperineal ultrasound assessment of LHap diameter changes are of certain value in the prediction of pelvic floor dysfunction and can provide objective and quantitative data support for clinicians to diagnose pelvic floor dysfunction. This study is highly innovative and scientific.

Emergence of the colistin resistance gene,mcr-1,has attracted worldwide attention.Despite the prevalence of mcr-1-positive Escherichia coli(MCRPEC)strains in human carriage showing a significant decrease between 2016 and 2019,genetic differences in MCRPEC strains remain largely unknown.We therefore conducted a comparative genomic study on MCRPEC strains from fecal samples of healthy human subjects in 2016 and 2019.We identified three major differences in MCRPEC strains between these two time points.First,the insertion sequenceISApll1 was often deleted and the percentage of mcr-1-carrying IncI2 plasmids was increased in MCRPEC strains in 2019.Second,the antibiotic resistance genes(ARGs),aac(3)-Ⅳa and blaCTX-M-1,emerged and coexisted with mcr-1 in 2019.Third,MCRPEC strains in 2019 contained more viru-lence genes,resulting in an increased proportion of extraintestinal pathogenic E.coli(ExPEC)strains(36.1％)in MCRPEC strains in 2019 compared to that in 2016(10.5％),implying that these strains could occupy intestinal ecological niches by competing with other commensal bacteria.Our results suggest that despite the significant reduction in the prevalence of MCRPEC strains in humans from 2016 to 2019,MCRPEC exhibits increased resistance to other clinically important ARGs and contains more virulence genes,which may pose a potential public health threat.