A 41-year-old female patient developed round,bright yellow patches on the left calvarial region without obvious precipitating factors 40 years prior to the presentation,which gradually grew to form plaques with age.Two years prior to the presentation,nipple-like lesions appeared in the calvarial and temporal region with an erythematous and wet surface; concurrently,black masses developed in the left temporal region and gradually enlarged with central ulceration but no subjective symptoms.At about 1 year of age,pitchy macules developed on the light tan patches located on the left jaw,posterior and anterior neck,trunk and upper limbs,and gradually increased in quantity and size with the involvement of the homolateral dorsal hand and gradual appearance of papules.Skin examination revealed two well-marginated,indurated,bright red neoplasms sized 3 cm × 2 cm and 2 cm × 1 cm respectively,with erosive and cauliflower-like surface; black or pink papules were scattered between these neoplasms.There was a ring-shaped black mass sized 1.5 cm × 1.5 cm in the left temporal region with central ulceration.Pitchy tough macules and papules were observed on the light tan patches located in the left cheek,lower mandible,posterior and anterior neck,protothorax,shoulder and back,upper limbs and dorsal hand.Based on the histopathology of multiple lesions,the cauliflower-like lesions on the head were diagnosed as syringocystadenoma papilliferum,the yellow plaques as syringocystadenoma papilliferum complicated by sebaceous adenoma,the black proliferative lesions in the temporal region as trichoblastoma accompanied by basal cell epithelioma,the black papuloid lesions and brown maculopapuloid lesions on the lower mandible as nevus spilus.The patient was diagnosed with skin adnexal tumor with multipotential differentiation (syringocystadenoma papilliferum,sebaceous adenoma,trichoblastoma and basal cell epithelioma)accompanied by nevus spilus.

Objective:To explore the application value of dynamic monitoring of gastric residual volume (GRV) in achieving different target energy in severe mechanical ventilation patients.Methods:A prospective randomized controlled study was conducted. Forty-two patients with mechanical ventilation admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from July to December 2022 were enrolled. According to the random number table method, patients were divided into GRV guided enteral nutrition by traditional gastric juice pumpback method (control group, 22 patients) and GRV guided enteral nutrition by bedside ultrasound (test group, 20 patients). General data were collected from both groups, and clinical indicators such as hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), neutrophil percentage (Neut%), procalcitonin (PCT), absolute lymphocytes (LYM), prealbumin (PA), and retinol-binding protein (RBP) were dynamically observed. Inflammation, infection, immunity, nutritional indicators, and the incidence of reflux/aspiration, ventilator-associated pneumonia (VAP) were compared between the two groups, and further compared the proportion of patients with respectively to reach the target energy 25%, 50%, and 70% on days 1, 3, and 5 of initiated enteral nutrition.Results:① There were no significant differences in gender, age, body mass index (BMI), duration of mechanical ventilation, and acute physiology and chronic health evaluationⅡ(APACHEⅡ), sequential organ failure assessment (SOFA), severe nutritional risk score (NUTRIC) at admission between the two groups, indicating comparability. ② On day 1 of initiated enteral nutrition, there were no significant differences in infection, inflammation, immunity and nutrition indicators between the two groups. On day 3 of initiated enteral nutrition, the hs-CRP in the test group was lower than that control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 129.60±75.18 vs. 185.20±63.74, LYM: 1.00±0.84 vs. 0.60±0.41, PA (mg/L): 27.30±3.66 vs. 22.30±2.55, all P < 0.05]. On day 5 of initiated enteral nutrition, the hs-CRP, Neut%, PCT in the test group were lower than those control group, LYM and PA were higher than those control group [hs-CRP (mg/L): 101.70±54.32 vs. 148.40±36.35, Neut%: (85.50±7.66)% vs. (92.90±6.01)%, PCT (μg/L): 0.7 (0.3, 2.7) vs. 3.6 (1.2, 7.5), LYM: 1.00±0.68 vs. 0.50±0.38, PA (mg/L): 27.10±4.57 vs. 20.80 ± 3.51, all P < 0.05]. There were no significantly differences in IL-6 and RBP between the two groups at different time points. ③ The proportion of 50% and 70% of achieved target energy in the test group on day 3, day 5 of initiated enteral nutrition were higher than those of the control group (70.0% vs. 36.4%, 70.0% vs. 36.4%, both P < 0.05). ④ The incidence of reflux/aspiration and VAP in the test group on day 5 of initiated enteral nutrition were significantly lower than those control group (incidence of reflux/aspiration: 5.0% vs. 28.6%, incidence of VAP: 10.0% vs. 36.4%, both P < 0.05). Conclusion:Dynamic monitoring of GRV by bedside ultrasound can accurately improve the proportion of 50% of achieved target energy on day 3 and 75% on day 5 in severe mechanical ventilation patients, improve the patient's inflammation, immune and nutritional status, and can prevent the occurrence of reflux/aspiration and VAP.

Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.

Abstract: Synthetic cannabinoids (SCs) are synthetic psychoactive substances that can pose a public health risk. The SCs are structurally variable and susceptible to structural modification. The rapid emergence of structurally unknown synthetic cannabinoids has led to new challenges in their identification. In recent years, machine learning has made great progress and has been widely applied to other fields, providing new strategies for the identification of unknown synthetic cannabinoids and the inference of possible sources. This paper describes the principles of commonly used machine learning methods and the application of machine learning techniques to mass spectrometry, Raman spectroscopy, metabolomics and quantitative conformational relationships of synthetic cannabinoids, aiming to provide new ideas for the identification of unknown synthetic cannabinoids.

Objective:To explore the value of current indications for fetal pulmonary valvuloplasty (FPV) by summarizing the postnatal diagnosis, treatment, and prognosis of fetuses with pulmonary atresia with intact ventricular septum (PA/IVS) and right ventricular hypoplasia (RVH).Methods:This prospective study was conducted at the Heart Center of Women and Children's Hospital, Qingdao University from September 2018 to March 2021, which included pregnant women who were (1) with fetal PA/IVS and RVH; (2) unable to receive FPV due to fetal position or gestational age despite the indications; (3) given integrated pre- and postnatal management. Prenatal fetal echocardiography assessment, postnatal diagnosis, treatment, and follow-up were summarized using Wilcoxon matched-pair signed-rank test.Results:A total of 35 singleton pregnant women were diagnosed with fetal PA/IVS and RVH by ultrasonic cardiogram and admitted during the study period. Among the 28 fetuses meeting the FPV indications, 18 underwent FPV, while the other 10 did not due to inappropriate fetal position or gestational age. After excluding four terminated pregnancies, the rest six cases were enrolled. The median gestational age at the initial prenatal fetal echocardiography diagnosis was 28.9 weeks (28.3-30.4 weeks). Compared with the initial evaluation, the fetal right ventricular to left ventricular length/diameter ratio [0.8 (0.6-0.9) vs 0.6 (0.5-0.8)] and tricuspid regurgitation velocity [4.7 m/s (3.2-5.1 m/s) vs 4.1 m/s (3.3-4.8 m/s)] were increased, while tricuspid valve Z value [－0.8(－1.6-0.8) vs 0.4 (－0.3-1.9)] and single-ventricular predictive score [0.5 (0.0-2.0) vs 2.0 (1.0-3.0)] were decreased when re-evaluated six weeks later ( T were－2.21, 2.00,－2.20, and 2.00; all P<0.05). All of the six fetuses were born alive with a median gestational age of 38.9 weeks (37.3-40.1 weeks). The median weight was 3 425 g (3 100-4 160) g after being transferred to cardiac intensive care unit. The median age was 12.5 d (0.0-20.0 d) at the first surgical intervention. The median follow-up duration was 15 months (11.8-18.5 months). At initial diagnosis, the single-ventricular predictive score was 1-2 points in four fetuses, and =3 points in two fetuses. There was no death during follow-up. Four patients achieved anatomical biventricular circulation, one achieved clinical biventricular circulation, and one still needed further follow-up, with single-ventricular predictive score at initial diagnosis of 1-3, 3, and 2 points, respectively. Conclusions:The prognosis is good in fetuses with PA/IVS and RVH who have FPV indications but do not receive intrauterine intervention, which suggests that the current FPV indications may be too broad, and a more suitable FPV indication need to be further explored given the difficulty of implementing FPV.

AIM: To explore the potential mechanism of action of Pingxiao capsule in the treatment of breast cancer. METHODS: TCMSP, TCM-ID, GeneCards and other databases were used to screen the related targets of Pingxiao capsule and breast can-

AIM: To investigate the ability of quercetin to reverse acquire adriamycin (ADR) resistance and explored its probably mechanism. METHODS: The CCK-8 assay was used to detect the cytotoxicity of quercetin in MCF-7/ADR cells and the reversal effect of ADR. The colony formation assay and Hoechst 332582 staining were used to detect the cell proliferation, cell apoptosis and the accumulation of rhodamine 123 (Rh123) respectively. The RNA expression levels of GAS5 and ABCB1 were detected by qRT-PCR. The protein expression levels of GSK-3β, β-catenin, c-MYC, cyclin D1, and ABCB1 were detected by Western blot. RESULTS: Quercetin (10, 20, 40 μmol/L) significantly enhanced the sensitivity of MCF-7/ADR to ADR, inhibitd cell proliferation, and increased the intracellular accumulation of Rh123. Treatment with quercetin in MCF-7/ADR cells, the expression levels of GAS5 and GSK-3β were increased, whereas the expression levels of β-catenin, c-myc, cyclin D1 and ABCB1 were decreased. Further research revealed that reduction of GAS5 by RNA interference (si-GAS5) induced inhibitory effects on the expressions of GAS5 and GSK-3β, and enhanced the expressions of β-catenin, c-myc, cyclin D1, and ABCB1. Furthermore, treatment by quercetin combined with si-GAS5 in MCF-7/ADR cells, the expressions of these proteins were effectively reversed in comparison to quercetin combined with siRNA negative control (sncRNA). CONCLUSION: Quercetin increases the expression of GAS5by GSK-3β/β-catenin signaling pathway, which inhibits the expression of ABCB1, ultimately reversing ADR resistance in the MCF-7/ADR cells.

Objective : To explore the mechanism of Prunella vulgaris and Scutellaria barbata herb pair against breast cancer based on network pharmacology and in vitro cell experiments． Methods : The effective components and targets of Prunella vulgaris and Scutellaria barbata herb pair were screened．GeneCards and OMIM databases were used to find breast cancer targets，and then drug-active ingredient-key target network and protein-protein inter- action (PPI) were constructed. R language was used to perform GO function and KEGG pathway enrichment analy- sis and survival analysis．Then the screened active components and core targets were verified by molecular docking. Cell viability was detected by CCK-8 assay．EdU and flow cytometry were used to detect cell proliferation and apop- tosis．The protein expression levels of p-AKT1，AKT1，β-catenin and c-MYC were detected by Western blot. Results : Through databases analysis，a total of 36 active components and 105 intersection targets were screened out，the core components were quercetin，luteolin，kaempferol，wogonin and baicalein．Through PPI and survival analysis，the key targets were AKT1，ESR1，CASP3 and MYC．GO analysis contained 4 303 enrichment results，KEGG analysis contained 232 pathways．Molecular docking showed that the core components had strong binding ability with the key targets．Cell experiments showed that the core active ingredient quercetin could inhibit the proliferation of breast cancer cells and promote their apoptosis (P＜0. 05) ，and down-regulate the expression levels of p-AKT1，β-catenin and c-MYC proteins (P＜0. 05) ． Conclusion The active components quercetin in Prunella vulgaris and Scutel- laria barbata herb pair may play a role through AKT1 / β-catenin signaling pathway，which provides a scientific refer- ence for the study of its mechanism of action in the treatment of breast cancer.

Leptin, an adipocyte-derived peptide hormone, has been shown to facilitate breathing. However, the central sites and circuit mechanisms underlying the respiratory effects of leptin remain incompletely understood. The present study aimed to address whether neurons expressing leptin receptor b (LepRb) in the nucleus tractus solitarii (NTS) contribute to respiratory control. Both chemogenetic and optogenetic stimulation of LepRb-expressing NTS (NTS^LepRb) neurons notably activated breathing. Moreover, stimulation of NTS^LepRb neurons projecting to the lateral parabrachial nucleus (LPBN) not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTS^LepRb neurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTS^LepRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTS^LepRb neuron stimulation. In brainstem slices, bath application of leptin rapidly depolarized the membrane potential, increased the spontaneous firing rate, and accelerated the Ca²⁺ transients in most NTS^LepRb neurons. Therefore, leptin potentiates breathing in the NTS most likely via an NTS-LPBN-preBötC circuit.
Leptin/pharmacology* ; Membrane Potentials ; Neurons/metabolism* ; Solitary Nucleus/metabolism*

Amino Acid Substitution ; Antineoplastic Agents/pharmacology* ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; Gastrointestinal Neoplasms/pathology* ; Humans ; MAP Kinase Signaling System/genetics* ; Mutation, Missense ; Receptor, ErbB-3/metabolism* ; Receptor, Fibroblast Growth Factor, Type 1/metabolism*