This paper summarizes the clinical experience in the syndrome differentiation and treatment of rosacea using the method of venting heat and resolving stagnation. It is considered that the key pathogenesis of rosacea is the accumulation of heat with stagnation. Accordingly， the method of venting heat and resolving stagnation is proposed， which vents and disperses constraint heat by applying approaches such as dredging defensive qi， clearing qi， venting ying （营） level， and cooling blood， while eliminating stagnation and masses through regulating qi， resolving dampness， dispelling phlegm and removing stasis. In clinical practice， a core prescription for venting heat and resolving stagnation is formulated， with flexible modifications made according to the clinical characteristics of different rosacea subtypes， including erythematotelangiectatic， papulopustular， phymatous， and ocular types， thereby providing therapeutic insights for the treatment of rosacea with traditional Chinese medicine.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Objective:The SARS-CoV-2 has a high natural mutation rate, and dynamic monitoring of virus variants remains a key focus in current COVID-19 prevention and control efforts.Methods:In this study, a sensitive and rapid method for detecting SARS-CoV-2 omicron variant nucleic acid was established based on the BMD-PCR technology.Results:This method showed good specificity, and had no cross-reactivity with 11 common viruses transmitted via the respiratory and gastrointestinal tracts, and the limit of detection is 555 copies/ml. Compared with SARS-CoV-2 whole-genome sequencing result, among 50 samples with original Ct values ≤32 tested for the Omicron variant, 49 samples tested positive for the N679K mutation site using BMD-PCR Omicron variant detection, achieving a concordance rate of 98.00%. For 30 samples JN.1 lineage, 29 samples tested positive for the K356T mutation site using BMD-PCR JN.1 lineage detection, with a concordance rate of 96.67%. For 10 samples with original SARS-CoV-2 detection Ct values between 35 and 32, 7 samples tested positive for the N679K mutation site using BMD-PCR Omicron variant detection, Resultsing in a detection rate of 70.00%. For samples with SARS-CoV-2 nucleic acid detection Ct values>35, the detection rate for the N679K mutation site in the BMD-PCR Omicron variant was 20.00%.Conclusions:This method can serve as a high-throughput supplementary approach for the preliminary identification of SARS-CoV-2 variant genotypes.

Objective:To examine the near-complete genomic analysis of norovirus (NoV) subtype GⅡ.17 [P17] outbreaks in Beijing Chaoyang District from 2014 to 2024.Methods:Data and specimens related to outbreaks of the NoV aggregation in Beijing′s Chaoyang District from 2014 to 2024 were collected. The NoV was identified using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). Specimens with positive nucleic acid were amplified by standard PCR, whole genome sequencing and evolutionary analysis. Amino acid site variations were compared.Results:In Chaoyang District, from 2014 to 2024, a total of 637 aggregated outbreaks caused by the NoV infection were reported, of which 584 were successfully typed. The epidemic caused by the GⅡ.17 [P17] subtype accounted for 8.79% (56/637), which was the dominant epidemic gene subtype in 2014-2015, sporadic in 2016-2019, reappeared in 2022, and significantly increased in 2024 (27.27%, 24/88). Outbreaks caused by the GⅡ.17 [P17] subtype occurred mainly from October to December, with the main sites of occurrence in primary schools and kindergartens. This study yielded 53 near-complete genome sequences of the GⅡ.17 [P17] subtype from 46 incidents in Chaoyang District. The GⅡ.17 [P17] subtype sequences of Chaoyang District from 2014 to 2024 were segmented into three subgroups on the evolutionary tree, with sequences from 2014 to 2019, 2022 to April 2024, and May to December 2024 clustered into the d, e, and b subgroups, respectively. In the VP1 region′s P2 area, particularly at the HBGA binding site, subgroups b and e exhibited mutations in 22 and two sites, while subgroups b and e showed mutations in four and one sites, predominantly in the RdRp region.Conclusion:The outbreak caused by the NoV GⅡ.17 [P17] subtype in Chaoyang District from 2014 to 2024 continues, with a significant increase in 2024, and it becomes the dominant gene subtype from October to December. The sequence formation of the NoV GⅡ.17 [P17] subtype in Chaoyang District from January to April 2022 and from May to December 2024 shows two different evolutions, with specific mutation sites, requiring continuous monitoring of the NoV GⅡ.17 [P17] subtype.

Objective:To investigate the effects of musculoskeletal ultrasound(MSUS)-guided shoulder joint capsule hydraulic expansion method combined with rotator interval(RI)injection method on ultrasound imaging indicators,shoulder function,and serum inflammatory factors in treating patients with early primary frozen shoulder(PFS).Methods:A total of 168 patients with early PFS admitted to Jiangbei District of The Frist Affiliated Hospital to Army Medical University between June 2021 and June 2023 were selected.They were randomly divided into a control group and an observation group by using a random number table,with 84 patients in each group.The control group received the therapy with MSUS-guided shoulder joint capsule hydraulic expansion.The observation group received the therapy with RI injection on the basis of the control group.After 5 weeks of treatment,the changes of the following parameters were compared and analyzed between the two groups:Visual Analog Scale(VAS)score for shoulder pain,Simple Shoulder Test(SST)score,Constant-Murley Score(CMS),thickness of the glenohumeral joint capsule at the axilla of ultrasound imaging,thickness of coracohumeral ligament(CHL),RI thickness,positivity rate of RI blood flow,passive range of motion(ROM)of the shoulder joint,and serum inflammatory factor levels including tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)and interleukin-6(IL-6).Results:At 5th week after treatment,both groups showed VAS scores decreased,and SST and CMS scores increased.The VAS score(1.34±0.30)of observation group was significantly lower than(1.97±0.46)of control group,and the SST score and CMS score were significantly higher than those of control group(t=10.514,9.597,7.910,P<0.05),respectively.Both groups showed decreases in thickness of the glenohumeral joint capsule at the axilla,CHL thickness,RI thickness,and positivity rate of RI blood flow,and these indicators of observation group were significantly lower than them of control group,with statistically significant differences(t=5.518,16.106,9.050,25.211,P<0.05).The ranges of backward extension and outward rotation of observation group were larger than those of control group,and the differences were statistically significant(t=9.209,12.447,P<0.05).The serum levels of TNF-α,IL-6 and CRP of observation group were significantly lower than those of control group,and the differences were statistically significant(t=10.523,17.750,19.995,P<0.05),respectively.Conclusion:The treatment of MSUS-guided shoulder joint capsule hydraulic expansion combined with RI injection can effectively alleviate the degrees of shoulder pain and dysfunction in patients with early PFS,and improve indicators of ultrasound imaging,the ROM values of outward rotation and backward extension,and reduce serum levels of inflammatory factors,which have favorable therapeutic effects.

Objective:To establish a fluorescent quantitative RT-PCR assay based on N_sgRNA of SARS-CoV-2 and preliminarily apply it on real samples.Methods:Recombinant plasmid, specific primers and probes of N_sgRNA were designed and synthesized based on Wuhan-Hu-1/2019_MN908947 and synthesis mechanism of subgenomic RNA (sgRNA). Using recombinant plasmid as amplification templates, the optimal reaction conditions and reaction system were screened according to the Ct value, fluorescence intensity, and shape of amplification curve and was evaluated for sensitivity, reproducibility, and specificity. Meanwhile, the possibility of practical application of the method was explored by testing 172 clinical samples and 256 municipal wastewater samples. Results:A qRT-PCR assay for N_sgRNA in SARS-CoV-2 was initially established. The detection limit of the assay was 20 copies/mL, and the variation coefficients of in-batch (0.002%~0.767%) and batch to batch repetition (0.016%~0.752%) were less than 1%. Only N_sgRNA recombinant plasmid was detected in the specificity assay. So the method is more highly sensitive, specific and reproducible. The RatiosgRNA/ gRNA of clinical samples HK.3, EG.5.1, JN.1 and their sub-lineages and their corresponding urban sewage samples in epidemic period were significantly different ( P<0.05). There is a strong correlation between the median of RatiosgRNA/ gRNA in clinical samples and sewage samples in the same period (correlation coefficient r=1.000, P=0.010). Conclusions:In this study, a qRT-PCR method for detecting N_sgRNA of SARS-CoV-2 was established and the method has the characteristics of higher sensitivity, stronger specificity and better repeatability, and it can be used to detect SARS-CoV-2 infectivity.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

To analyze the distribution of serotypes and antimicrobial resistance of clinical Salmonella isolates from multiple centers across China.

Objective:To construct and evaluate the predictive performance of a multiphase ultrasound radiomics model for microvascular invasion（MVI）in hepatocellular carcinoma（HCC）.Methods:A total of 126 patients with pathologically confirmed HCC were retrospectively enrolled from 4 medical centers between May 2018 and July 2025，including the First Hospital of Shanxi Medical University，Shanxi Province Third People's Hospital，Changzhi People's Hospital，and the Organ Transplant Center of the Affiliated Hospital of Qingdao University. A total of 630 ultrasound images of the lesions in different phases were collected，from which 1 561 radiomic features were extracted. The patients from medical institutions in Shanxi Province were chosen as the training set（ n=91），and the patients from the Organ Transplant Center of the Affiliated Hospital of Qingdao University were chosen as the validation set（ n=35）. In the training set，37.4%（34/91）patients presented MVI（+），whereas in the validation set，54.3%（19/35）patients presented MVI（+）. Radiomics features were extracted from ultrasound images，and features related to the MVI（+）were selected through dimensionality reduction analysis. Five multiple machine learning algorithms were used to construct predictive models，which were then evaluated using an external validation set. The Radscore was calculated，and a nomogram was constructed combining Radscore with ultrasound and clinical characteristics to predict MVI. Results:The model combining radiomics features from the portal venous phase and the delay phase showed the best predictive performance in both the training and validation sets，with area under curve（AUC）values of 0.835 and 0.727，respectively. The prediction model developed using radiomics Radscore and clinical indicators could be represented and presented as a nomogram.Conclusions:The radiomics model based on multi-phase ultrasound offers a novel approach for non-invasive preoperative prediction of MVI in liver cancer. Furthermore，its integration with clinical features aids in optimizing clinical treatment strategies.

Objective To study the application of autologous natural killer(NK)cells in the treatment of advanced renal cell carcinoma and the changes of immune function and tumor markers in patients.Methods 61 patients with advanced renal cell carcinoma admitted to Gansu Wuwei Tumour Hospital from March 2023 to April 2024 were divided into targeting group(31 cases,given supportive treatment combined with sunitinib malate capsules)and cell group(30 cases,autologous NK cells combined with targeting group)according to the patient's willingness to treat combined with propensity score matching.6 weeks was a treatment cycle,and all patients were treated for 4 cycles.The clinical efficacy of the two groups after 4 cycles of treatment and the occurrence of adverse reactions during treatment were statistically analyzed.The levels of serum cytokines,tumor markers,lymphocyte function and immune function were compared between the two groups before and after 4 cycles of treatment.Results After 4 cycles of treatment,the objective remission rate and disease control rate in the cell group were higher than those in the targeting group(P<0.05).After 4 cycles of treatment,the levels of serum hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),platelet-derived growth factor(PDGF),carcinoembryonic antigen,carbohydrate antigen 125,carbohydrate antigen 199 and alpha-fetoprotein in the two groups were lower than those before treatment,and those in the cell group were lower than those in the targeting group(P<0.012 5).After 4 cycles of treatment,the levels of serum interleukin-2,interleukin-6,tumor necrosis factor-β,interferon-γ,peripheral blood CD3+,CD4+,NK cells and CD4+/CD8+in the two groups were higher than those before treatment.The levels of serum interleukin-2,tumor necrosis factor-β,interferon-γ,peripheral blood CD3+and NK cells in the cell group were higher than those in the targeting group(P<0.012 5).The level of CD8+in peripheral blood was lower than that before treatment(P<0.012 5),but there was no significant difference between the two groups(P>0.012 5).During the treatment,there was no significant difference in the incidence of diarrhea,nausea and vomiting,alopecia,liver function damage,decreased platelet level and decreased neutrophil level between the cell group and the targeting group(P>0.05).Conclusion The treatment of advanced renal cell carcinoma with autologous NK cells could improve the level of serum cytokines,reduce the level of tumor markers,regulate the function of lymphocytes and immune function,and had a good therapeutic effect.At the same time,it would not increase the incidence of adverse reactions,and the safety was good.