In recent years,immune checkpoint inhibitor(ICI)has led to substantial advances in the treatment of recurrent or metastatic advanced cutaneous melanoma(CM),significantly prolonging overall survival.However,due to the biological heterogeneity across melanoma subtypes,the degree of immune responsiveness varies considerably.In particular,acral melanoma(AM)(the predominant melanoma subtype in Asian populations,including China)has demonstrated limited benefit from ICI therapy,especially in the context of monotherapy.Currently,no systematic staging and standardized treatment guidelines are available for AM,and clinical evidence supporting the use of ICI in this rare subtype remains insufficient.In the neoadjuvant setting,several large phase Ⅱ/Ⅲ international trials in CM,including SWOG 1801 and NADINA,have shown that ICI-based neoadjuvant combination therapy significantly improves pathological response rates compared with traditional adjuvant approaches.Nevertheless,neoadjuvant treatment in AM remains in the exploratory stage.Early-phase clinical studies in resectable stage Ⅲ/Ⅳ AM suggest that toripalimab combined with intratumoral oncolytic virus therapy,or camrelizumab in combination with apatinib and temozolomide,may offer clinical benefit;however,confirmation of long-term survival benefit requires further validation in larger,prospective cohorts.In the adjuvant setting,for AM patients with BRAF mutations,real-world data from China have shown no significant difference in survival outcomes between dabrafenib plus trametinib and programmed death-1(PD-1)inhibitor monotherapy in high-risk resectable stage Ⅲ/Ⅳ disease,although direct head-to-head comparisons are lacking.For patients with resectable stage Ⅲ/Ⅳ wild-type AM,combination adjuvant regimens incorporating PD-1 inhibitors may provide superior recurrence risk reduction and survival benefit compared to monotherapy.In the advanced disease setting,in Chinese populations,the objective response rates of PD-1 inhibitors such as pembrolizumab,toripalimab and penpulimab remain suboptimal in AM.ICI-based combination strategies(including those with chemotherapy,anti-angiogenic agents,dual or triple immune checkpoint blockade)may improve the immune microenvironment and clinical prognosis,but concerns regarding safety and tolerability persist.For patients with ICI-refractory AM,various novel approaches combining immunotherapy,targeted agents and chemotherapy are under investigation.Additionally,several next-generation immunotherapeutic modalities[including T-cell receptor-engineered(TCR-T)therapies,therapeutic cancer vaccines,chimeric antigen receptor T(CAR-T)cell therapy and antibody-drug conjugate(ADC)]are currently in development.This review aimed to provide a comprehensive overview of current clinical evidence on the use of ICI in acral melanoma across the neoadjuvant,adjuvant,and advanced disease settings.We highlighted the efficacy and safety of existing strategies,exploreed emerging combination regimens and predictive biomarkers,and discussed key areas for future research to inform clinical decision-making and optimize outcomes in this challenging melanoma subtype.

In recent years,immune checkpoint inhibitor(ICI)has led to substantial advances in the treatment of recurrent or metastatic advanced cutaneous melanoma(CM),significantly prolonging overall survival.However,due to the biological heterogeneity across melanoma subtypes,the degree of immune responsiveness varies considerably.In particular,acral melanoma(AM)(the predominant melanoma subtype in Asian populations,including China)has demonstrated limited benefit from ICI therapy,especially in the context of monotherapy.Currently,no systematic staging and standardized treatment guidelines are available for AM,and clinical evidence supporting the use of ICI in this rare subtype remains insufficient.In the neoadjuvant setting,several large phase Ⅱ/Ⅲ international trials in CM,including SWOG 1801 and NADINA,have shown that ICI-based neoadjuvant combination therapy significantly improves pathological response rates compared with traditional adjuvant approaches.Nevertheless,neoadjuvant treatment in AM remains in the exploratory stage.Early-phase clinical studies in resectable stage Ⅲ/Ⅳ AM suggest that toripalimab combined with intratumoral oncolytic virus therapy,or camrelizumab in combination with apatinib and temozolomide,may offer clinical benefit;however,confirmation of long-term survival benefit requires further validation in larger,prospective cohorts.In the adjuvant setting,for AM patients with BRAF mutations,real-world data from China have shown no significant difference in survival outcomes between dabrafenib plus trametinib and programmed death-1(PD-1)inhibitor monotherapy in high-risk resectable stage Ⅲ/Ⅳ disease,although direct head-to-head comparisons are lacking.For patients with resectable stage Ⅲ/Ⅳ wild-type AM,combination adjuvant regimens incorporating PD-1 inhibitors may provide superior recurrence risk reduction and survival benefit compared to monotherapy.In the advanced disease setting,in Chinese populations,the objective response rates of PD-1 inhibitors such as pembrolizumab,toripalimab and penpulimab remain suboptimal in AM.ICI-based combination strategies(including those with chemotherapy,anti-angiogenic agents,dual or triple immune checkpoint blockade)may improve the immune microenvironment and clinical prognosis,but concerns regarding safety and tolerability persist.For patients with ICI-refractory AM,various novel approaches combining immunotherapy,targeted agents and chemotherapy are under investigation.Additionally,several next-generation immunotherapeutic modalities[including T-cell receptor-engineered(TCR-T)therapies,therapeutic cancer vaccines,chimeric antigen receptor T(CAR-T)cell therapy and antibody-drug conjugate(ADC)]are currently in development.This review aimed to provide a comprehensive overview of current clinical evidence on the use of ICI in acral melanoma across the neoadjuvant,adjuvant,and advanced disease settings.We highlighted the efficacy and safety of existing strategies,exploreed emerging combination regimens and predictive biomarkers,and discussed key areas for future research to inform clinical decision-making and optimize outcomes in this challenging melanoma subtype.

OBJECTIVE To understand the prevalence of non-bacterial pathogens infections among the children who were hospitalized in pediatrics department due to acute respiratory tract infections(ARTI)from 2020 to 2024.METHODS The children who were hospitalized in pediatrics department of Lishui People's Hospital due to ARTI from Mar.2020 to Feb.2024 were enrolled in the study,the results of tests of 13 items of respiratory tract patho-gens for the children were retrospectively analyzed.The positive isolation rates of respiratory tract pathogens and epidemiological characteristics were observed and compared among the children according to the gender,age and season.RESULTS A total of 12,291 children were enrolled in the study,6508 of whom were tested positive for re-spiratory tract pathogens,and the total positive isolation rate was 52.95％.Rhinovirus(HRV),Mycoplasma pneumoniae and respiratory syncytial virus(RSV)ranked the top 3 pathogens tested positive.The total positive rate of isolation of the male children was 54.43％(3707/6810),higher than 51.10％(2801/5481)of the female children(x2=13.524,P＜0.001);the positive rates of HRV and RSV of the male children were higher than those of the female children(P＜0.05),while the positive rate of MP of the female children was higher than that of the male children(P＜0.05).There was significant difference in the total positive rate of isolation of respirato-ry tract pathogens among the age groups(x2=59.924,P＜0.001).The positive rates of RSV,HRV and MP of the infant group,the toddler group,the preschool age group and the school age group were relatively high.The total positive rate of isolation of the respiratory tract pathogens showed an upward trend with the change of sea-sons(x2=145.887,P＜0.001);there was significant difference in the prevalence of pathogens among the seasons(P＜0.05).CONCLUSIONS HRV,MP and RSV are dominant among the respiratory tract non-bacterial patho-gens isolated from the children who are hospitalized in Lishui People's Hospital from 2020 to 2024.There are sig-nificant differences in the positive rates of the respiratory tract pathogens among the genders,age,and seasons.

OBJECTIVE To understand the prevalence of non-bacterial pathogens infections among the children who were hospitalized in pediatrics department due to acute respiratory tract infections(ARTI)from 2020 to 2024.METHODS The children who were hospitalized in pediatrics department of Lishui People's Hospital due to ARTI from Mar.2020 to Feb.2024 were enrolled in the study,the results of tests of 13 items of respiratory tract patho-gens for the children were retrospectively analyzed.The positive isolation rates of respiratory tract pathogens and epidemiological characteristics were observed and compared among the children according to the gender,age and season.RESULTS A total of 12,291 children were enrolled in the study,6508 of whom were tested positive for re-spiratory tract pathogens,and the total positive isolation rate was 52.95％.Rhinovirus(HRV),Mycoplasma pneumoniae and respiratory syncytial virus(RSV)ranked the top 3 pathogens tested positive.The total positive rate of isolation of the male children was 54.43％(3707/6810),higher than 51.10％(2801/5481)of the female children(x2=13.524,P＜0.001);the positive rates of HRV and RSV of the male children were higher than those of the female children(P＜0.05),while the positive rate of MP of the female children was higher than that of the male children(P＜0.05).There was significant difference in the total positive rate of isolation of respirato-ry tract pathogens among the age groups(x2=59.924,P＜0.001).The positive rates of RSV,HRV and MP of the infant group,the toddler group,the preschool age group and the school age group were relatively high.The total positive rate of isolation of the respiratory tract pathogens showed an upward trend with the change of sea-sons(x2=145.887,P＜0.001);there was significant difference in the prevalence of pathogens among the seasons(P＜0.05).CONCLUSIONS HRV,MP and RSV are dominant among the respiratory tract non-bacterial patho-gens isolated from the children who are hospitalized in Lishui People's Hospital from 2020 to 2024.There are sig-nificant differences in the positive rates of the respiratory tract pathogens among the genders,age,and seasons.

African swine fever virus (ASFV) infection leads to a mortality rate of up to 100%, causing devastating disasters to the pig industry. Understanding the ASFV infection and replication is therefore of great importance. ASFV has more than 150 open reading frames, among which the inner coat protein p17 encoded by the D117L gene is involved in the formation of the icosahedral structure of the virus. However, little is known about the mechanism how p17 regulates host cell function. In this study, the potential host proteins interacting with ASFV p17 were screened by immunoprecipitation technique combined with protein profiling analysis. The interactions of p17 with mitochondrial membrane protein TOMM70 and heat shock protein HSPA8 were confirmed by co-immunoprecipitation technique and laser confocal experiments. This study provides important information for further exploring the function of p17 during ASFV infection.
African Swine Fever ; African Swine Fever Virus/metabolism* ; Animals ; Open Reading Frames ; Swine ; Viral Proteins/metabolism*

Objective:To investigate the role of long-chain non-coding RNA MEG3 and DNA demethylase TET2 in the invasive growth of pituitary growth hormone (GH) adenomas, and provide research directions for the subsequent exploration of molecular biological mechanisms.Methods:All of 60 patients with GH pituitary adenomas diagnosed in Dalian Central Hospital from January 2016 to November 2019 were collected, and the normal anterior pituitary tissue samples of 10 patients with traumatic brain injury without neurological or endocrine system diseases were collected as control group. Real-time reverse transcription-polymerase chain reaction (qPCR) was used to detect the expression of lnc RNA MEG3 and TET2 in normal pituitary tissue as well as invasive and non-invasive pituitary growth hormone adenomas, and the differences between each groups were analyzed. At the same time, age and gender were included in the research, and the effects of age and gender on the invasive growth of pituitary GH adenomas were analyzed.Results:The aggressive growth of MEG3 and TET2 was independent of patients′ age and gender. The expression of lncRNA MEG3 in invasive pituitary GH adenoma and non-invasive pituitary GH adenoma was significantly lower than that in normal control brain tissue. Analysis of the differences between the groups found that the expression level of lncRNA MEG3 in normal trauma control pituitary tissues, non-invasive GH adenomas, and invasive GH adenomas were sequentially decreased, and MEG3 expression level was related to the aggressive growth behavior of pituitary GH adenomas ( P<0.05). The expression levels of DNA demethylase TET2 in invasive pituitary GH adenomas and non-invasive pituitary GH adenomas were significantly lower than those in the normal control brain tissue, and the expression levels in the three groups of samples gradually decreased ( P<0.05). It suggested that the expression of lncRNA MEG3 was positively correlated with the expression of DNA demethylase TET2. Conclusions:The low expression of lncRNA MEG3 and DNA demethylase TET2 is closely related to the aggressiveness of pituitary growth hormone adenoma.

Objective: To understand the health literacy and relevant factors of cancer prevention consciousness in Chinese urban residents from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The self-designed questionnaire was used to collect the information of demographic characteristics and cancer prevention consciousness focusing on nine common risk factors, including smoking, alcohol, fiber food, food in hot temperature or pickled food, chewing betel nut, helicobacter pylori, moldy food, hepatitis B infection, estrogen, and exercise. The logistic regression model was adopted to identify the influencing factors. Results: The overall health literacy of the cancer prevention consciousness was 77.4% (24 980 participants), with 77.4% (12 018 participants), 79.9% (6 406 participants), 77.2% (1 766 participants) and 74.5% (4 709 participants) in each group (P<0.001). The correct response rates for nine risk factors ranged from 55.2% to 93.0%. The multivariate logistic regression analysis showed that compared with community residents, people with primary school level education or below, and the number of people living together in the family <3, the cancer risk assessment/screening intervention population, cancer patients, those with junior high school level educationor above and the number of people living in the family ≥3 had better health literacy of the cancer prevention consciousness (all P values <0.05). Compared with females, 39 years old and below, government-affiliated institutions or civil servants, from the eastern region, males, older than 40 years, company or enterprise employees, and from the middle or western region had worse health literacy of the cancer prevention consciousness (all P values <0.05). Conclusion The health literacy of the cancer prevention consciousness in Chinese urban residents should be improved. The cancer screening intervention, gender, age, education, occupation, the number of people co-living in the family, and residential region were associated with the health literacy of the cancer prevention consciousness.

Scutellaria baicalensis (S. baicalensis) and Scutellaria barbata (S. barbata) are common medicinal plants of the Lamiaceae family. Both produce specific flavonoid compounds, including baicalein, scutellarein, norwogonin, and wogonin, as well as their glycosides, which exhibit antioxidant and antitumor activities. Here, we report chromosome-level genome assemblies of S. baicalensis and S. barbata with quantitative chromosomal variation (2n = 18 and 2n = 26, respectively). The divergence of S. baicalensis and S. barbata occurred far earlier than previously reported, and a whole-genome duplication (WGD) event was identified. The insertion of long terminal repeat elements after speciation might be responsible for the observed chromosomal expansion and rearrangement. Comparative genome analysis of the congeneric species revealed the species-specific evolution of chrysin and apigenin biosynthetic genes, such as the S. baicalensis-specific tandem duplication of genes encoding phenylalanine ammonia lyase and chalcone synthase, and the S. barbata-specific duplication of genes encoding 4-CoA ligase. In addition, the paralogous duplication, colinearity, and expression diversity of CYP82D subfamily members revealed the functional divergence of genes encoding flavone hydroxylase between S. baicalensis and S. barbata. Analyzing these Scutellaria genomes reveals the common and species-specific evolution of flavone biosynthetic genes. Thus, these findings would facilitate the development of molecular breeding and studies of biosynthesis and regulation of bioactive compounds.
Evolution, Molecular ; Flavonoids/biosynthesis* ; Genome, Plant ; Plant Extracts/genetics* ; Scutellaria/metabolism* ; Whole Genome Sequencing

Objective To evaluate the prognostic significance of extent of resection (EOR) in patients with gradeⅢglioma, and the MRI sequence best related with tumor volume. Methods Ninety-six cases were studied retrospectively who were diagnosed as glioma of grade Ⅲ gliomas at Dalian Medical University Affiliated Hospital of Dalian Municipal Central Hospital during the period from 2010 to 2015. EOR was calculated using preoperative and postoperative contrast-enhanced T1-weighted and T2-weightedfluid attenuated inversion recovery (T2Flair) MR images. Univariate and multivariate analyses were performed to evaluate the correlation between EOR and overall survival (OS). Results The results of univariate analysis showed that patients with age<50 years(P=0.032), preoperative KPS>80 scores (P<0.01), no edema (P=0.005), postoperative chemotherapy (P<0.01) and T2Flair EOR≥68% (P<0.01) had better prognosis. Cox multivariate regression analysis showed that age(P=0.008), edema (P＝0.003), postoperative chemotherapy(P=0.000) and T2Flair EOR (P=0.004) were independent factors of prognosis for grade Ⅲ glioma patients. Conclusions T2Flair-EOR is one of the most significant prognostic predictors in patients with grade Ⅲ gliomas. An important survival advantage is associated with T2Flair-EOR≥68% for patients with gradeⅢgliomas.

OBJECTIVETo evaluate the clinical therapeutic effects and safety on rheumatoid arthritis (RA) treated with acupuncture at the points detected with thermosensitive moxibustion in medicine combined with western medication.

METHODSA total of 168 RA patients in compliance with the inclusive criteria were collected and randomized into an observation group and a control group, 84 cases in each one. In the control group, in reference to the updated guideline of new drugs by the European League Against Rheumatism (EULAR) in 2013, the medication scheme was formulated for oral administration, methotrexate tablet 7.5 mg, once a week; salazosulfapyridine enteric-coated tablets, 100 mg, twice a day; hydroxychloroquine sulfate tablets, 20 mg, twice a day; and meloxicam tablets, 15 mg, once a day. In the observation group, besides the treatment as the control group, the acupuncture therapy at the points detected with thermosensitive moxibustion in medicine was given. The mild moxibustion was applied near to the affected joint with the moxa material of herbal medicine to detect the sensitization points. Afterwards, the acupuncture technique of medicine was given on those points, without any manipulation applied. The needles were retained for 30 min, once daily. The treatment for 2 weeks was as one course, continuously for 2 courses. The indexes were observed before and after treatment in the two groups including gripping power, the time of morning stiffness, the swollen joint count 28 (SJC 28), the tender joint count 28 (TJC 28), the disease activity score 28 (DAS 28), the score of patient global assessment of disease activity (PtGA) and the score of provider global assessment of disease activity (PhGA), as well as rheumatoid factors (RF), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anti-cyclic peptide containing citrulline (A-CCP). The clinical therapeutic effects were evaluated in the two groups.

RESULTSAfter 4-week treatment, a total of 163 patients accomplished the clinical trial, 81 cases in the observation group and 82 cases in the control group. The results of gripping power, the time of morning stiffness, SJC 28, TJC 28, PtGA, PhGA, DAS 28, RF, CRP, ESR and A-CCP were all improved as compared with those before treatment (all <0.05). In 4 weeks of treatment, the results of gripping power, the time of morning stiffness, SJC 28, TJC 28, PtGA, PhGA, DAS 28, as well as CRP and ESR in the observation group were better than those in the control group (all <0.05). The results of RF and A-CCP were not different significantly between the two groups (both >0.05). The total effective rate was 85.19% (69/81) in the observation group, higher than 70.73% (58/82) in the control group (<0.05).

CONCLUSIONThe acupuncture therapy at the points detected with thermosensitive moxibustion in medicine achieves the satisfactory clinical effects with few adverse effects.