Testing region selection and prognostic analysis of MLH1 promoter methylation in colorectal cancer in China.

Background: MLH1 promoter methylation analysis is recommended in screening for Lynch syndrome (LS) in patients with MLH1-deficient colorectal cancer (CRC). The study aims to identify specific methylation regions in the MLH1 promoter and to evaluate the clinicopathologic characteristics of and prognosis for patients with MLH1 methylation. Methods: A total of 580 CRC cases were included. The DNA mismatch repair (MMR) protein expression was assessed by using immunohistochemistry (IHC). The methylation status of the Regions A, B, C, D, and E in the MLH1 promoter was tested by using bisulfite sequencing PCR. The specificities of the five regions were calculated. Associations between MLH1 methylation and clinicopathologic characteristics were evaluated. Kaplan-Meier analyses for overall survival (OS) were carried out. Results: In 580 CRC cases, the specificities of the methylation test in Regions D and E were both 97.8%. In the MLH1-deficient CRCs, the frequencies of MLH1 methylation and BRAFV600E mutation were 52.6% and 14.6%, respectively; BRAFV600E mutation occurred in 27.7% of patients with MLH1-methylated CRC. In the MMR-deficient patients, compared with MLH1 unmethylation, MLH1 methylation was more common in patients who were aged ≥50 years, female, had no family history of LS-related tumors, and had tumors located at the right colon. In the MMR-deficient patients, the MLH1-methylated cases had lower OS rates than the unmethylated cases with a family history of LS-related tumors (P = 0.047). Conclusions: Regions D and E in the MLH1 promoter are recommended for determining the MLH1 methylation status in screening for LS in MLH1-deficient CRC. In MMR-deficient patients, the MLH1-methylated cases had a worse OS than the unmethylated cases with a family history of LS-related cancer.

Stability analysis of rainfall-induced landslide considering air resistance delay effect and lateral seepage.

Accumulation landslides are prone to occur during the continuous infiltration of heavy rainfall, which seriously threatens the lives and property safety of local residents. In this paper, based on the Green-Ampt (GA) infiltration model, a new slope rainfall infiltration function is derived by combining the effect of air resistance and lateral seepage of saturated zone. Considering that when the soil layer continues to infiltrate after the saturation zone is formed, the air involvement cannot be discharged in time, which delays the infiltration process. Therefore, the influence of air resistance factor in soil pores is added. According to the infiltration characteristics of finite long slope, the lateral seepage of saturated zone is introduced, which makes up for the deficiency that GA model is only applicable to infinite long slope. Finally, based on the seepage characteristics of the previous analysis, the overall shear strength criterion is used to evaluate the stability of the slope. The results show that the safety factor decreases slowly with the increase of size and is inversely correlated with the slope angle and initial moisture content. The time of infiltration at the same depth increases with the increase of size and slope angle, and is inversely correlated with the initial moisture content, but is less affected by rainfall intensity. By comparing with the results of experimental data and other methods, the results of the proposed method are more consistent with the experimental results than other methods.

Debris flow volume prediction model based on back propagation neural network optimized by improved whale optimization algorithm.

Debris flow is a sudden natural disaster in mountainous areas, which seriously threatens the lives and property of nearby residents. Therefore, it is necessary to predict the volume of debris flow accurately and reliably. However, the predictions of back propagation neural networks are unstable and inaccurate due to the limited dataset. In this study, the Cubic map optimizes the initial population position of the whale optimization algorithm. Meanwhile, the adaptive weight adjustment strategy optimizes the weight value in the shrink-wrapping mechanism of the whale optimization algorithm. Then, the improved whale optimization algorithm optimizes the final weights and thresholds in the back propagation neural network. Finally, to verify the performance of the final model, sixty debris flow gullies caused by earthquakes in Longmenshan area are selected as the research objects. Through correlation analysis, 4 main factors affecting the volume of debris flow are determined and inputted into the model for training and prediction. Four methods (support vector machine regression, XGBoost, back propagation neural network optimized by artificial bee colony algorithm, back propagation neural network optimized by grey wolf optimization algorithm) are used to compare the prediction performance and reliability. The results indicate that loose sediments from co-seismic landslides are the most important factor influencing the flow of debris flows in the earthquake area. The mean absolute percentage error, mean absolute error and R2 of the final model are 0.193, 29.197 × 104 m3 and 0.912, respectively. The final model is more accurate and stable when the dataset is insufficient and under complexity. This is attributed to the optimization of WOA by Cubic map and adaptive weight adjustment. In general, the model of this paper can provide reference for debris flow prevention and machine learning algorithms.

Prognosis and immunotherapy efficacy in dMMR&MSS colorectal cancer patients and an MSI status predicting model.

The inconsistency between mismatch repair (MMR) protein immunohistochemistry (IHC) and microsatellite instability PCR (MSI-PCR) methods has been widely reported. We aim to investigate the prognosis and the effect of immunotherapy in dMMR by IHC but MSS by MSI-PCR (dMMR&MSS) colorectal cancer (CRC) patients. A microsatellite instability (MSI) predicting model was established to help find dMMR&MSS patients. MMR and MSI states were detected by the IHC and MSI-PCR in 1622 CRC patients (ZS6Y-1 cohort). Logistic regression analysis was used to screen clinical features to construct an MSI-predicting nomogram. We propose a new nomogram-based assay to find patients with dMMR&MSS, in which the MSI-PCR assay only detects dMMR patients with MSS predictive results. We applied the new strategy to a random cohort of 248 CRC patients (ZS6Y-2 cohort). The consistency of MMR IHC and MSI-PCR in the ZS6Y-1 cohort was 95.7% (1553/1622). Both pMMR&MSS and dMMR&MSS groups experienced significantly shorter overall survival (OS) than those in dMMR by IHC and MSI-H by MSI-PCR (dMMR&MSI-H) group (hazard ratio [HR] = 2.429, 95% confidence interval [CI]: 1.89-3.116, p < .01; HR = 21.96, 95% CI: 7.24-66.61, p < .01). The dMMR&MSS group experienced shorter OS than the pMMR&MSS group, but the difference did not reach significance (log rank test, p = .0686). In the immunotherapy group, the progression-free survival of dMMR&MSS patients was significantly shorter than that of dMMR&MSI-H patients (HR = 13.83, 95% CI: 1.508-126.8, p < .05). The ZS6Y-MSI-Pre nomogram (C-index = 0.816, 95% CI: 0.792-0.841, already online) found 66% (2/3) dMMR&MSS patients in the ZS6Y-2 cohort. There are significant differences in OS and immunotherapy effect between dMMR&MSI-H and dMMR&MSS patients. Our prediction model provides an economical way to screen dMMR&MSS patients.

Risk of CKD among patients with DM taking diuretics or SGLT2i: a retrospective cohort study in Taiwan.

BACKGROUND: This study aimed to evaluate the long-term risk of CKD and renal function declines using a combination of diuretics and SGLT2i. METHODS: We selected the data of subjects who had at least two outpatient records or at least one inpatient record for DM treatment as the DM group from the National Health Insurance Research Database (NHIRD). Patients receiving versus not receiving SGLT2i were defined as the SGLT2i and non-SGLT2i cohorts, respectively. The patients in the two groups were matched 1:1 through propensity score matching based on age, sex, year of index date, and comorbidities. RESULTS: The diuretics-only group had a higher risk of CKD (aHR, 2.46; 95% CI, 1.68-3.61) compared to the neither SGLT2i nor diuretics group, while the both SGLT2i and diuretics group and the SGLT2i only group had lower risks (aHR, 0.45, 95% CI, 0.32-0.63; aHR, 0.26, 95% CI, 0.17-0.40) than the diuretics-only group. The SGLT2i-only group had a lower risk (aHR, 0.58, 95% CI, 0.36-0.94) than the both SGLT2i and diuretics group. CONCLUSION: This study indicates that diuretics could raise the risk of CKD in diabetic patients, but when used in combination with SGLT2i, they continue to offer protection against CKD.

Inserting an "atomic trap" for directional dopant migration in core/multi-shell quantum dots.

Diffusion of atoms or ions in solid crystalline lattice is crucial in many areas of solid-state technology. However, controlling ion diffusion and migration is challenging in nanoscale lattices. In this work, we intentionally insert a CdZnS alloyed interface layer, with small cationic size mismatch with Mn(ii) dopant ions, as an "atomic trap" to facilitate directional (outward and inward) dopant migration inside core/multi-shell quantum dots (QDs) to reduce the strain from the larger cationic mismatch between dopants and host sites. Furthermore, it was found that the initial doping site/environment is critical for efficient dopant trapping and migration. Specifically, a larger Cd(ii) substitutional site (92 pm) for the Mn(ii) dopant (80 pm), with larger local lattice distortion, allows for efficient atomic trapping and dopant migration; while Mn(ii) dopant ions can be very stable with no significant migration when occupying a smaller Zn(ii) substitutional site (74 pm). Density functional theory calculations revealed a higher energy barrier for a Mn(ii) dopant hopping from the smaller Zn substitutional tetrahedral (Td) site as compared to a larger Cd substitutional Td site. The controlled dopant migration by "atomic trapping" inside QDs provides a new way to fine tune the properties of doped nanomaterials.

Interfacial B-Site Ion Diffusion in All-Inorganic Core/Shell Perovskite Nanocrystals.

All-inorganic metal halide perovskites (ABX3, X = Cl, Br, or I) show great potential for the fabrication of optoelectronic devices, but the toxicity and instability of lead-based perovskites limit their applications. Shell passivation with a more stable lead-free perovskite is a promising strategy to isolate unstable components from the environment as well as a feasible way to tune the optical properties. However, it is challenging to grow core/shell perovskite nanocrystals (NCs) due to the soft ionic nature of the perovskite lattice. In this work, we developed a facile method to grow a lead-free CsMnCl3 shell on the surface of CsPbCl3 NCs to form CsPbCl3/CsMnCl3 core/shell NCs with enhanced environmental stability and improved photoluminescence (PL) quantum yields (QYs). More importantly, the resulting core/shell perovskite NCs have color-tunable PL due to B-site ion diffusion at the interface of the core/shell NCs. Specifically, B-site Mn diffusion from the CsMnCl3 shell to the CsPbCl3 core leads to a Mn-doped CsPbCl3 core (i.e., Mn:CsPbCl3), which can turn on the Mn PL at around 600 nm. The ratio of Mn PL and host CsPbCl3 PL is highly tunable as a function of the thermal annealing time of the CsPbCl3/CsMnCl3 core/shell NCs. While the halide anion exchange for all-inorganic metal halide perovskites has been well-developed for band-gap-engineered materials, interfacial B-site diffusion in core/shell perovskite NCs is a promising approach for both tunable optical properties and enhanced environmental stability.

Exposure to Air Pollutants Increases the Risk of Chronic Rhinosinusitis in Taiwan Residents.

Air pollution triggers a tissue-specific inflammatory response. However, studies on the association between exposure to air pollutants and chronic rhinosinusitis (CRS) risk remain limited. Thus, we conducted this nationwide study to define the association between air pollution and CRS. We used the Longitudinal Health Insurance Database (LHID) and Taiwan Air Quality-Monitoring Database (TAQMD) to conduct a population-based cohort study. Study participants were recruited from the LHID, a data subset of the National Health Insurance Research Database that randomly sampled one million individuals. TAQMD has been an air pollutant database since 1998. In univariate and multivariate Cox proportional hazards regression models, adjusted hazard ratios (aHRs) and 95% CIs of CRS in five air pollutants were accounted. We adjusted for age, sex, urbanization level, insurance fee, comorbidities, and pollutant levels in the multivariate model. The total number of participants enrolled in this study was 160,504. The average age was 40.46 ± 14.62 years; males constituted 43.8% of the total participants. The percentages of alcoholism, tobacco dependence, and COPD were 1.5%, 2.8%, and 28.3%, respectively. After adjustment for age, sex, urbanization level, insurance fee, and comorbidities, the highest levels of air pollutants, including PM2.5 (aHR = 1.14, 95% CI = 1.06-1.22), NO2 (aHR = 1.07, 95% CI = 1.00-1.15), and PM10 (aHR = 1.13, 95% CI = 1.05-1.21) had a significantly greater CRS risk; we selected the lower concentration as the reference but did not correlate with CO. We found a significantly increased risk of CRS in residents with air pollutant exposure.

Long-Term Exposure to Air Pollution Associates the Risk of Benign Brain Tumor: A Nationwide, Population-Based, Cohort Study in Taiwan.

Air pollutants as risk factors for benign brain tumor (BBT) remain unclear. Therefore, we conducted a nationwide retrospective cohort study by integrating the patients' clinical data and daily air quality data to assess the environmental risk factors of BBT in Taiwan.Daily air quality data were categorized into quartiles (Q1 to Q4). The adjusted hazard ratio (aHR) was evaluated by comparing the BBT incidence rate of the subjects in Q2-Q4 with that of the subjects in Q1 (the lowest concentration of air pollutants). A total of 161,213 subjects were enrolled in the study. Among the air pollutants tested, the aHR of BBT was significantly higher in the subjects who were exposed to the highest level (Q4) of CO (aHR 1.37, 95% CI 1.08-1.74), NO2 (aHR 1.40, 95% CI 1.09-1.78), and PM2.5 (aHR 1.30, 95% CI 1.02-1.65) than that in the subjects who were exposed to the lowest level (Q1). No significant risk association of BBT with SO2 and PM10 exposure was observed. The results revealed that long-term exposure to air pollutants, particularly CO, NO2, and PM2.5, is associated with the risk of BBT.

Cervical lymphatic malformations amenable to transhairline robotic surgical excision in children: A case series.

ABSTRACT: Lymphatic malformations are rare benign malformations that predominantly occur in the head and neck region. The advent of surgical robots in head and neck surgery may provide beneficial outcomes for pediatric patients. Here, we describe our experiences with transhairline incisions for robot-assisted surgical resection of cervical lymphatic malformations in pediatric patients.In this prospective longitudinal cohort study, we recruited consecutive patients under 18 years of age who were diagnosed with congenital cervical lymphatic malformations and scheduled for transhairline approach robotic surgery at a single medical center. We documented the docking times, console times, surgical results, complications, and postoperative follow-up outcomes.The studied patients included 2 with mixed-type lymphatic malformations and 2 with macrocystic-type lymphatic malformations. In all 4 patients, the incision was hidden in the hairline; the incision length was <5 cm in 3 patients but was extended to 6 cm in 1 patient. Elevating the skin flap and securely positioning it with Yang retractor took <1 hour in all cases. The mean docking time was 5.5 minutes, and the mean console time was 1 hour and 46 minutes. All 4 surgeries were completed endoscopically with the robot. The average total drainage volume in the postoperative period was 21.75 mL. No patients required tracheotomy or nasogastric feeding tubes. Neither were adverse surgery-associated neurovascular sequelae observed. All 4 patients were successfully treated for their lymphatic malformations, primarily with robotic surgical excisions.Cervical lymphatic malformations in pediatric patients could be accessed, properly visualized, and safely resected with transhairline-approach robotic surgery. Transhairline-approach robotic surgery is an innovative method for meeting clinical needs and addressing esthetic concerns.

The Spectrum, Tendency and Predictive Value of PIK3CA Mutation in Chinese Colorectal Cancer Patients.

BACKGROUND: PIK3CA is a high-frequency mutation gene in colorectal cancer, while its prognostic value remains unclear. This study evaluated the mutation tendency, spectrum, prognosis power and predictive power in cetuximab treatment of PIK3CA in Chinese CRC cohort. METHODS: The PIK3CA exon 9 and 20 status of 5763 CRC patients was detected with Sanger sequencing and a high-resolution melting test. Clinicopathological characteristics of 5733 patients were analyzed. Kaplan-Meier method and nomogram were used to evaluate the overall survival curve and disease recurrence, respectively. RESULTS: Fifty-eight types of mutations in 13.4% (771/5733) of the patients were detected. From 2014 to 2018, the mutation rate of PIK3CA increased from 11.0% to 13.5%. At stage IV, exon 20 mutated patients suffered shorter overall survival time than wild-type patients (multivariate COX regression analysis, HR = 2.72, 95% CIs = 1.47-5.09; p-value = 0.012). At stage III, PIK3CA mutated patients were more likely to relapse (multivariate Logistic regression analysis, exon 9: OR = 2.54, 95% CI = 1.34-4.73, p = 0.003; exon 20: OR = 3.89, 95% CI = 1.66-9.10, p = 0.002). The concordance index of the nomogram for predicting the recurrence risk of stage III patients was 0.685. After cetuximab treatment, the median PFS of PIK3CA exon 9 wild-type patients (n = 9) and mutant patients (n = 5) did not reach a significant difference (3.6 months vs. 2.3 months, Log-rank test, p-value = 0.513). CONCLUSIONS: We found that PIK3CA mutation was an adverse predictive marker for the overall survival of stage IV patients and recurrence of stage III patients, respectively. Further more, we suggested that PIK3CA exon 9 mutations are not negative predictors of cetuximab treatment in KRAS, NRAS, and BRAF wild-type mCRC patients.

Cervical malignant teratoma masquerading as a hematoma: a case report.

BACKGROUND: Post-pubertal teratomas, which mostly occur at 20 to 40 years old, are more likely to be found at a metastatic site in up to 20% of cases and may be inadvertently overlooked. We present a case of cervical malignant teratoma that masqueraded as a hematoma.Case presentation: A 24-year-old man presented to our institution with a 4-month history of a progressively relapsing painless mass in the neck, despite conservative treatments with oral medications. A huge space-occupying mass was identified with almost total occlusion of the left internal jugular vein. The likely diagnosis was an organized hematoma or congenital cystic tumor with internal hemorrhage. Surgical excisional biopsy of the mass lesion was conducted and a malignant teratoma was found. A whole-body positron emission tomography scan showed a left inguinal mass, bilateral intra-abdominal lymphadenopathies, and abdominal metastases. Histopathology further suggested the diagnosis of an immature testicular teratoma with multiple lymph node metastases. The patient received adjuvant chemotherapy with a bleomycin, etoposide, and cisplatin regimen. During follow-up, salvage second-line chemotherapy was required with a paclitaxel, ifosfamide, and cisplatin regimen. CONCLUSION: Although uncommon, cervical teratoma should be taken into consideration once a painless and non-remitting mass lesion is found in a young adult.

Surface-Enhanced Infrared Absorption of Ligands on Colloidal Gold Nanowires through Resonant Coupling.

Pushing the detection limit of infrared absorption (IR) through surface-enhanced (SEIRA) approaches have far-reaching prospect for related applications in molecular analysis and detection. Specifically engineered Au nanowires (NWs) can be applied as the surface-enhancing substrates in colloidal solution, given their longitudinal surface plasmon resonance (SPR) being aspect-ratio dependent and extendable into the infrared region. Through carefully designed control experiments, we realized resonant coupling between the longitudinal surface plasmons of Au NWs and the vibration modes of the bonded oleylamine (OA) ligands. In our system, after deliberately tuning thickness of the OA ligands and ratio of the detached/attached ligands in the solution, the apparent enhancement factor of IR signal from ligands around Au NWs could be pushed up to 5.29 × 104. Given the facile tuning of SPR properties of Au NWs in the colloidal solution and the performance demonstrated in the report, our work could be an intriguing platform for SEIRA implementations in a broad spectrum of circumstances.

KRAS G12V Mutation is an Adverse Prognostic Factor of Chinese Gastric Cancer Patients.

This study aims to investigate the molecular characteristics of Chinese gastric cancer patients. In our study, the KRAS, BRAF, and PIK3CA mutation status of 485 GC patients were analyzed by Sanger sequencing. Kaplan-Meier analysis was used to plot survival curves according to different genotypes. The results show that the frequency of KRAS, BRAF and PIK3CA mutations were 4.1%, 1.2% and 3.5%, respectively. BRAF mutations were significantly concentrated in stage III and IV gastric cancer (P=0.009). KRAS G12V mutation carriers have much shorter OS than other mutation carriers and wild-type group patients (P=0.013). In conclusion, only the KRAS G12V mutation has an adverse effect on patient survival.

Demographic trends and KRAS/BRAFV600E mutations in colorectal cancer patients of South China: A single-site report.

The incidence of colorectal cancer (CRC) is increasing in China. Here, we aimed to evaluate the latest demographic trends and KRAS/BRAF mutations status of Chinese CRC. Five thousand five hundred and forty-six CRC patients diagnosed from 2010 to 2017 were involved. KRAS exon 2 and BRAFV600E mutations were detected by Sanger sequencing and high-resolution melting analysis or allelic-specific probe method. Gene mutation profiles and clinicopathologic characteristics of 5495 patients were analyzed. The joinpoint regression model was used to predict the demographic data in 2018. We found KRAS exon 2 and BRAFV600E mutation rates were 37.7 and 2.8% in CRC patients. Tumors with KRAS exon 2 mutations were more likely to be present in female and patients aged older than 75 years, right colon and have well-differentiated histology. Tumors with BRAFV600E mutations were more likely to be present in the female, right colon and have poorly differentiated histology. From 2010 to 2017, the percentage of colon cancer and tubular adenocarcinoma in CRC increased substantially (from 39.3 to 51.8%, from 78.6 to 93.4%, respectively). The percentage of right colon cancer increased from 18.3 to 20.5%, which predictively may keep at 22.6% in 2018. The rise trends for patients with moderate differentiation tumor or KRAS exon 2 mutated tumor were apparent (from 50.3 to 78.6%, from 32.8 to 39.7%, respectively). In conclusion, in recent 8 years, there is a shift to the colon, especially right colon in the incidence of Chinese CRC. Moreover tubular adenocarcinoma is becoming the primary histology type.

Formula PSORI-CM01 inhibits the inflammatory cytokine and chemokine release in keratinocytes via NF-κB expression.

Psoriasis is a common chronic inflammatory disease in which T-helper 1(Th1) and T-helper 17(Th17) cells play an important role in its pathology. Formula PSORI-CM01 was a novel formulated Chinese medicine used for psoriasis therapy. It had been demonstrated previously that PSORI-CM01 and serum contained Formula PSORI-CM01 (PCM01CS) could improve psoriasis by inhibiting the epithelial hyperplasia, how PSORI-CM01 affects inflammatory cytokine and chemokine in dermis is still unknown. In this study we found PSORI-CM01 pre-treated 3days before IMQ painting could ameliorated IMQ-induced mice skin lesion as PASI score was apparently reduced. Th1 related cytokine IFN-γ and Th17 related cytokine IL-17/IL-22 was used to induce inflammatory models on human keratinocyte cell line HaCaT in vitro, respectively. PCM01CS significantly reduced IFN-γ induced mRNA expression of IL-6, IL-12 and CXCL-10, reduced IL-6 and CXCL-10 release into HaCaT supernatant. 20ng/ml IL-17/IL-22 co-stimulation significantly upregulated expression of IL-6, IL-8 and CCL20 mRNA expression in HaCaT cells, PCM01CS significantly inhibit these cytokines expression both in mRNA and in protein levels. Finally, PCM01CS could obviously inhibit nuclear NF-κB p65 expression which activated by IFN-γ and IL-17/IL-22 stimulation. Thus, our new findings reveal that Formula PSORI-CM01 may possess therapeutic action on psoriasis by inhibiting inflammatory within skin environments.

Sijunzi Decoction attenuates 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats and ameliorates TNBS-induced claudin-2 damage via NF-κB pathway in Caco2 cells.

BACKGROUND: SijunziDecoction (SJZD) is a traditional Chinese medicine prescription used to treat the diseases of gastrointestinal tract since ancient times. The objective of this study was to investigate the protective effects of SJZD on TNBS-induced colitis in rats and TNBS-damaged Caco2 cells. METHODS: The rat colitis model was induced by 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). SJZD (2.8 5.6, 11.2 g/kg) or salazosulfapyridine (SASP) (0.4 g/kg) was administrated orally in rats for 7 days. DAI, pathological scores and the expression of claudin-2 were evaluated. Then we explored the effect and mechanism of SijunziDecoction Serum (SJZDS) onTNBS-damaged Caco2 cells to figure out intestinal barrier protective effect and mechanism of SJZD. RESULTS: SJZD significantly ameliorated the severity of TNBS-induced colitis and downregulated the level of claudin-2 in colonic tissues. SJZDS promoted proliferation and inhibited apoptosis ofTNBS-damaged Caco2 cells. In Caco2 cell monolayers, we provided mechanistic evidence that SJZDS-induced increased TEER and decreased permeability after TNBS damage, which were mediated through claudin-2 and NF-κB pathway, including the upregulation of claudin-2, decreased activity of NF-κB p65, reduced level of NF-κB p65 and MLCK. CONCLUSIONS: Our results indicated that SJZD possesses protective effect of intestinal barrier towards TNBS-induced colitis in rats and TNBS-damaged Caco2 cells in vitro. SJZDis a potential protective agent of intestinal barrier that deserves further investigation.

Formula PSORI-CM01 eliminates psoriasis by inhibiting the expression of keratinocyte cyclin B2.

BACKGROUND: Psoriasis is a chronically recurrent inflammatory skin disease, modern medicine could achieve good therapeutic effect, but these treatments led to recurrence of the psoriasis, more severe symptoms due to damaging skin barrier. Traditional Chinese medicine is a useful alternative therapies. The purpose of this study was to explore the mechanism of PSORI-CM01, a Chinese medicine formula for psoriasis therapy, in eliminating psoriasis by studying its effects on inhibiting epidermal hyperplasia. METHODS: Imiquimod induced psoriasis-form mice model was used to determine the efficacy of PSORICM-01 by assessing the improvement of hyperplasia in epidermal and dermal skin, cyclin B2 expression in skin was detected by immunochemistry. Human keratinocyte cell line HaCaT stimulated by LPS or not was used to research molecular mechanisms of PSORIMCM-01 as in vitro model. The inhibition of proliferation of HaCaT was determined by MTT assay, BrdU assay and real-time cell analysis (RTCA). Cell cycle distribution was detected by flow cytometry. Real-Time PCR and western blot analysis was performed to quantify the mRNA and protein expression levels, respectively. The ability of PSORICM-01 to inhibit proliferation of cyclin B2 overexpressed HaCaT cell were also investigated. RESULTS: PSORI-CM01 significantly inhibited epidermal hyperplasia in IMQ mice lesion skin, and reduced expression of epidermis cyclin B2. Serum containing PSORI-CM01 dramatically inhibited keratinocyte HaCaT cell proliferation, no matter stimulated by LPS or not. FACS analysis showed ability of PSORICM-01 to arrest cell cycle in the G2/M phase. Additionally, PSORI-CM01 significant downregulated mRNA and protein expression of cyclin B2, and over-expression of cyclin B2 antagonized the anti-proliferative effect of PSORI-CM01 on HaCaT cells. CONCLUSIONS: PSORI-CM01 inhibits epidermal hyperplasia in imiquimod-induced mouse psoriasis-form model and reduces keratinocyte proliferation in vitro. Our results indicate that PSORI-CM01 may possess therapeutic potential for psoriasis by inhibiting keratinocyte proliferation through downregulation of cyclin B2.