ObjectiveTo investigate the mechanism of topical treatment of allergic contact dermatitis （ACD） mice with Portulacae Herba based on the nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/nuclear factor-κB （NF-κB） signaling pathway. MethodsA total of 70 6-week-old specific pathogen free （SPF） female Kunming mice were adaptively fed for 1 week and randomly divided into blank group， model group， compound dexamethasone acetate cream group （2.075×10^-2 g·g^-1）， blank matrix cream group， low-dose Portulacae Herba cream group （0.1 g·g^-1）， high-dose Portulacae Herba cream group （0.2 g·g^-1）， and Portulacae Herba + inhibitor group （0.2 g·g^-1 + 30 mg·kg^-1 ML385）， with 10 mice in each group. One day before the experiment， the mice were shaved on the neck and back. Except for the blank group， the mice in the other groups were treated with 2，4-dinitrochlorobenzene （DNCB） to establish an ACD model. After respective administration， the skin lesion of the mice was scored， and the histopathological changes of the skin were stained with hematoxylin-eosin （HE）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， reactive oxygen species （ROS）， superoxide dismutase （SOD） activity， and malondialdehyde （MDA） in serum of mice. The expression of Nrf2/HO-1/NF-κB signaling pathway-related proteins in mouse skin tissue was detected by immunohistochemistry （IHC）， Western blot， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， the mice in the model group had an increased skin lesion score （P<0.01）， severe pathological damage to skin tissue， increased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and decreased content of SOD （P<0.01）. In addition， the mRNA and protein expression levels of Nrf2， HO-1， and nuclear factor-κB inhibitor α （IκBα） in skin tissue were up-regulated （P<0.01）， while the protein expression levels of phosphorylated （p）-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.01）. Compared with the model group and the blank matrix cream group， the mice treated with Portulacae Herba had a decreased skin lesion score （P<0.01）， reduced pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in their serum （P<0.01）， and increased content of SOD （P<0.01）. Additionally， the mRNA and protein expression levels of Nrf2， HO-1， and IκBα in skin tissue were down-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were up-regulated （P<0.05，P<0.01）. Compared with the Portulacae Herba + inhibitor group， the high-dose Portulacae Herba cream group had a decreased skin lesion score （P<0.01）， alleviated pathological damage to skin tissue， decreased content of IL-1β， IL-6， ROS， and MDA in the serum of mice （P<0.05，P<0.01）， and increased content of SOD （P<0.01）. The protein expression levels of Nrf2， HO-1， and IκBα and the mRNA expression of Nrf2 and HO-1 in skin tissue were up-regulated （P<0.05，P<0.01）， and the protein expression levels of p-IκBα and p-NF-κB p65 and the mRNA expression of NF-κB p65 were down-regulated （P<0.05）. ConclusionPortulacae Herba can improve DNCB-induced ACD skin damage in mice by regulating the Nrf2/HO-1/NF-κB signaling pathway.

OBJECTIVE To study the effects and mechanism of Portulaca oleracea cream on skin pruritus and barrier function in allergic contact dermatitis （ACD） mice. METHODS Low-concentration and high-concentration P. oleracea creams were prepared， with the P. oleracea extract solution （1 g/mL， calculated by crude drug） concentrations of 10% and 20%. Sixty BALB/c mice were randomly allocated into blank group， model group， Mometasone furoate cream group （positive control）， blank matrix cream group， P. oleracea low-concentration and high-concentration cream groups. Except for blank group， ACD model was induced in each group using 2，4-dinitrochlorobenzene solution. The blank group and model groups received normal saline， while the remaining groups were treated with their respective creams， once a day， at a dose of approximately 0.5 g per application， continuously for 14 days. At 24 h post-final administration， skin lesions of mice were observed and scored； pathological changes of skin tissue were observed； serum levels of immunoglobulin E（IgE） and tumor necrosis factor-α （TNF-α） were quantified. mRNA expression of MAS-related G protein-coupled receptors （including MrgprA3， MrgprC11， and MrgprD） in dorsal root ganglion （DRG） was assessed； while protein expressions of skin barrier function-related proteins Claudin-1 and Occludin in skin tissues were determined. RESULTS Compared with blank group， mice in the model group exhibited severe skin damage， characterized by loss of epidermal architecture， hyperkeratosis of the skin tissue， and the infiltration of a large number of inflammatory cells. The skin injury scores， as well as the serum levels of IgE and TNF-α， and the mRNA expression levels of MrgprA3， MrgprC11， and MrgprD in DRG， were all significantly elevated compared to the blank group （P＜0.05 or P＜0.01）； in contrast， the protein expression levels of Claudin-1 and Occludin in the skin tissue were markedly reduced （P＜0.05）. Compared with model group， mice in P. oleracea low-concentration and high- concentration cream groups demonstrated significant alleviation of skin damage， as evidenced by reduced epidermal hyperplasia， mitigated spongiosis in the dermis， and decreased infiltration of inflammatory cells； these quantitative indicators were almost significantly reversed （P＜0.05 or P＜0.01）. No significant differences were observed in the aforementioned skin injuries， pathological alterations， or quantitative indicators between the blank matrix cream group and the model group. CONCLUSIONS P. oleracea may ameliorate skin lesions and restore skin barrier function of ACD mice， the mechanism of which may be associated with downregulating mRNA expressions of MrgprA3， MrgprC11 and MrgprD in DRG， and up-regulating the protein expressions of Claudin-1 and Occludin in skin tissue.

Objective To understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.

AIM:To investigate the effect of icari-in on renal fibrosis and injury in hypertension through Cx32-Nox4 signaling pathway.METHODS:Models of hypertensive nephropathy(HN)were es-tablished in spontaneously hypertensive rats(SHRs).The experiment was divided into 4 groups:normal control group(WKY rats),model group(SHR),icariin 10 mg·kg-1·d-1 group(icariin once dai-ly),icariin 30 mg·kg-1·d-1 group(icariin once daily),n=10.The expression of fibrosis-related proteins was detected in vivo.NRK-52E cells exposed to An-gⅡ were selected to observe the effects of icariin on kidney injury.Extracellular matrix(ECM)levels,including α-smooth muscle actin(α-SMA),collagenⅠ(Col-Ⅰ)and fibronectin(FN)expression were mea-sured by Western blot and immunohistochemistry.The expressions of oxidative stress markers includ-ing superoxide dismutase(SOD)and malondialde-hyde(MDA)were determined by the test kit.RE-SULTS:Icariin reduced renal fibrosis in SHR rats in vivo.Icariin down-regulated the expression of α-SMA,FN,and Col-Ⅰ and protected hypertension-damaged kidney tissue from progressive fibrosis(P＜0.05).Icariin increased the total SOD activity and decrease the MDA level in kidney and serum of SHR rats(P＜0.05).In addition,icariin increased the expression of Cx32 and decreased the expression of Nox4 in the kidneys of SHR rats(P＜0.05).Icariin had a protective effect on AngⅡ-mediated NRK-52E cell damage and fibrosis.CONCLUSION:Icariin can improve renal tubulointerstitial fibrosis and delay the progression of HN.Renal protection may be at-tributed to the regulation of oxidative stress medi-ated by the Cx32-Nox4 signaling pathway.

Objective:To investigate the predictive value of thyroid peroxidase antibody(TPOAb), thyroglobulin antibody(TgAb), and thyrotropin receptor antibody(TRAb) status prior to the first 131I treatment in the development of hypothyroidism in patients with Graves′ disease after 131I administration. Methods:The cohort of 89 males and 351 females, with a median age of 34 years (IQR 28-44) who underwent initial 131I therapy at Peking Union Medical College Hospital from December 2019 to December 2021 was established. Participants were classified into TPOAb-positive, TgAb-positive, TRAb-positive, and their respective negative groups based on pre-treatment serum levels of thyroid autoantibody. Sex, age, medical history, thyroid hormone level, thyroid autoantibodies, iodine uptake rate, thyroid estimation and 131I treatment dose were recorded. The 131I treatment dose was determined using the calculated dose method. Patients were followed up for one-year post-treatment to evaluate efficacy. Mann- Whitney U test and χ 2 test were used to compare and analyze the data between groups, and logistic regression was used to analyze the influencing factors of permanent hypothyroidism after treatment. Results:(1) In the TPOAb-positive group, transient hypothyroidism and permanent hypothyroidism occurred in 8.1%(26/321) and 44.9%(144/321), both of which were significantly higher than those in the TPOAb-negative group at 2.5%(3/119) and 31.9%(38/119); In the TRAb-negative group, permanent hypothyroidism occurred in 56.8%(25/44), which was significantly higher than that in the TRAb-positive group 39.5%(152/385). (2) After the first 131I treatment, males ( OR=0.518, 95% CI 0.314-0.855, P=0.010), TPOAb-positive ( OR=1.002, 95% CI 1.001-1.003, P=0.001), and TRAb-negative( OR=0.973, 95% CI 0.957-0.990, P=0.002) were independent influence factor, of permanent hypothyroidism. Conclusion:In the calculated dose method for treating GD, male, TPOAb-positivity, and TRAb-negativity prior to initial 131I treatment are associated with a higher likelihood of developing permanent hypothyroidism post-treatment.

Port-wine stains (PWS) are one of the common congenital vascular malformations in dermatology, clinically manifesting as pink or red irregular patches occurring on the skin or mucosa at birth or shortly thereafter, which are often not elevated above the skin surface. In a minority of patients, vascular malformations not only affect the skin, but also involve the eyes, brain, limbs and viscera. These patients are at risk for glaucoma, epilepsy, limb pain, and other clinical conditions. In general, these conditions are referred to as PWS-associated syndromes. These syndromes are rare diseases, can affect multiple systems and exhibit a variety of clinical manifestations, which pose challenges in their diagnosis and treatment. This review focuses on the clinical manifestations, diagnoses, pathogenesis and treatment of PWS-associated syndromes.

Port-wine stains (PWS) are vascular malformations characterized by dilated capillaries and postcapillary venules in the skin. Clinically, they mainly manifest as pink or red irregular patches, most of which may become thickened, darkened in color, or even develop into nodules over age, making treatment more challenging. The mechanisms underlying the development and progression of PWS are not very clear, and may be related to heredity, gene mutations, abnormal ratios of blood vessels to nerves, etc. This review summarizes research progress in the mechanisms underlying the development and progression of PWS, so as to provide a theoretical basis for their treatment.

Objective To explore the comparison of the predictive value of three risk assessment tools on the chemotherapy-induced nausea and vomiting(CINV)in cancer patients.Methods From January 2022 to December 2022,convenience sampling was used to select 626 cancer patients with Intravenous chemotherapy in the Department of Hepatobiliary Pancreatic Oncology of Zhejiang Cancer Hospital as the research object.CINV risk assessment of patients was performed using George teams acute CINV prediction tool,Dranitsari's CINV risk assessment and CINV nomogram model.Area under curve(AUC),sensitivity,specificity and Youden index were used to compare the predictive value of the three tools.Results Totally 622 patients were ultimately included in the study,with an overall effective rate of 99.36%.There were 51.13%(318/622)patients who experienced CINV.Specifically,patients with grade 2 or higher acute CINV accounted for 18.17%(113/622).When using the three tools for acute CINV risk assessment,the AUC was respectively 0.591,0.616 and 0.558.And Dranitsari's CINV risk assessment has the highest sensitivity,acute and delayed chemotherapy-induced nausea and vomiting prediction tool has the highest specificity.Comparatively,Dranitsari's CINV risk assessment on the Yorden index is better.Conclusion The incidence of CINV in cancer patients is at a high level.The three tools can not effectively predict the risk of acute CINV.We need to develop a localized,multi-disease,standardized CINV risk assessment model for hospital.

Objective To investigate the habits of eye rubbing and sleeping posture of patients with keratoconus(KC)and analyze the correlation of the onset and severity of KC with eye rubbing and sleeping posture.Methods In this retrospective case-control study,KC patients who received diagnosis and treatment in the Eye Hospital of Shandong First Medical University from January 2018 to June 2022 were collected as the KC group,and myopia patients with matching ages and sexes who visited our hospital from February to June 2022 were recruited as the control group.All patients were inves-tigated by questionnaire and the details of eye rubbing,sleeping posture and related habits were recorded.According to the severity of the disease(corneal curvature),KC patients were divided into different stages,and the eye rubbing and sleep-ing posture of KC patients in different stages were compared.Results In this study,406 KC patients and 394 myopia pa-tients were included.It was found that 67.98％of KC patients and 24.87％of myopia patients rubbed their eyes,with a sig-nificant difference(P＜0.001);45.32％of KC patients and 24.87％of myopia patients were accustomed to sleeping on their side or stomach,with a significant difference(P＜0.001).The multivariate binary logistic regression analysis indica-ted that the following variables showed significant differences:patients with eyes at the later stages(steeper eyes)were more likely to rub eyes[odds ratio(OR)=3.547,95％CI:2.02-6.24,P＜0.001],sleep on side or stomach(OR=10.725,95％CI:5.77-19.94,P＜0.001),and turn head to the steeper eye when sleeping(OR=12.171,95％CI:7.23-20.49,P＜0.001).The statistical analysis demonstrated that the proportion of KC patients at the IV stage who were habitu-ated to rub their steeper eyes and turn their heads to the steeper eyes when sleeping was significantly higher than that of pa-tients at stages Ⅰ to Ⅲ(all P＜0.001).Conclusion Eye rubbing and sleeping on the side or stomach are risk factors for the onset of KC and are related to the severity of the disease.

Objective:To understand the gene carrying rate of neonatal genetic deafness in Dalian area, and to analyze the pedigree of 6 newborns with positive deafness gene test, to provide a reference basis for preventing genetic deafness.Methods:A total of 1 536 newborns born in Dalian Women′s and Children′s Medical Center (Group) from January to October in 2022 were retrospectively enrolled to detect the 4 genes of hereditary deafness, including GJB2, GJB3, SLC26A4 (PDS) and MT-RNRI (12SrRNA). Among them, 6 newborns with hereditary deafness were tested for NGS Panel gene.Results:A total of 85 deafness gene mutations were detected in 1 536 newborns, with the total carrying rate of 5.53% (85/1 536). Thirty-two cases of GJB2 mutations with carrying rate of 2.08% (32/1 536); 4 cases of GJB3 mutation of 0.26% (4/1 536); 32 cases of SLC26A4 (PDS) gene mutations of 2.08% (32/1 536); 14 cases of MT-RNRI (12SrRNA) mutations with carrying rate of 0.91% (14/1 536); 2 cases had compound heterozygous mutations of GJB2/GJB3, with a carrier rate of 0.13% (2/1 536); 1 cases had compound heterozygous mutations of GJB2/SLC26A4 (PDS), with a carrier rate of 0.07% (1/1 536); 1 case of compound heterozygous mutation in three-gene and a heterozygous mutation in KCNQ4 were detected in NGS Panel testing for hereditary deafness.Conclusions:Homozygous mutation and compound heterozygous mutation are the main factors of autosomal recessive gene deafness, and the NGS Panel gene detection is of great significance for gene traceability and the detection of rare deafness gene.