Recent Advances in Targeted Therapies for Infantile Hemangiomas.

Targeted therapy for infantile hemangiomas (IHs) has been extensively studied as they can concentrate drugs, increase therapeutic efficacy and reduce drug dosage. Meanwhile, they can extend drug release times, enhance drug stability, decrease dosing frequency, and improve patient compliance. Moreover, carriers made from biocompatible materials reduced drug immunogenicity, minimizing adverse reactions. However, current targeted formulations still face numerous challenges such as the non-absolute safety of carrier materials; the need to further increase drug loading capacity; the limitation of animal hemangioma models in fully replicating the biological properties of human infantile hemangiomas; the establishment of models for deep-seated hemangiomas with high incidence rates; and the development of more specific targets or markers. In this review, we provided a brief overview of the characteristics of IHs and summarized the past decade's advances, advantages, and targeting strategies of targeted drug delivery systems for IHs and discussed their applications in the treatment of IHs. Furthermore, the goal is to provide a reference for further research and application in this field.

Pre-treatment risk predictors of valproic acid-induced dyslipidemia in pediatric patients with epilepsy.

Background: Valproic acid (VPA) stands as one of the most frequently prescribed medications in children with newly diagnosed epilepsy. Despite its infrequent adverse effects within therapeutic range, prolonged VPA usage may result in metabolic disturbances including insulin resistance and dyslipidemia. These metabolic dysregulations in childhood are notably linked to heightened cardiovascular risk in adulthood. Therefore, identification and effective management of dyslipidemia in children hold paramount significance. Methods: In this retrospective cohort study, we explored the potential associations between physiological factors, medication situation, biochemical parameters before the first dose of VPA (baseline) and VPA-induced dyslipidemia (VID) in pediatric patients. Binary logistic regression was utilized to construct a predictive model for blood lipid disorders, aiming to identify independent pre-treatment risk factors. Additionally, The Receiver Operating Characteristic (ROC) curve was used to evaluate the performance of the model. Results: Through binary logistic regression analysis, we identified for the first time that direct bilirubin (DBIL) (odds ratios (OR) = 0.511, p = 0.01), duration of medication (OR = 0.357, p = 0.009), serum albumin (ALB) (OR = 0.913, p = 0.043), BMI (OR = 1.140, p = 0.045), and aspartate aminotransferase (AST) (OR = 1.038, p = 0.026) at baseline were independent risk factors for VID in pediatric patients with epilepsy. Notably, the predictive ability of DBIL (AUC = 0.690, p < 0.0001) surpassed that of other individual factors. Furthermore, when combined into a predictive model, incorporating all five risk factors, the predictive capacity significantly increased (AUC = 0.777, p < 0.0001), enabling the forecast of 77.7% of dyslipidemia events. Conclusion: DBIL emerges as the most potent predictor, and in conjunction with the other four factors, can effectively forecast VID in pediatric patients with epilepsy. This insight can guide the formulation of individualized strategies for the clinical administration of VPA in children.

[Establishment and Evaluation Strategy of an in vitro Cell Model of Bone Marrow Microenvironment Injury in Mouse Acute Graft-Versus-Host Disease].

OBJECTIVE: To establish a mesenchymal stem cell（MSC）-based in vitro cell model for the evaluation of mouse bone marrow acute graft-versus-host disease (aGVHD). METHODS: Female C57BL/6N mice aged 6-8 weeks were used as bone marrow and lymphocyte donors, and female BALB/c mice aged 6-8 weeks were used as aGVHD recipients. The recipient mouse received a lethal dose (8.0 Gy,72.76 cGy/min) of total body γ irradiation, and injected with donor mouse derived bone marrow cells (1×107/mouse) in 6-8 hours post irradiation to establish a bone marrow transplantation (BMT) mouse model (n=20). In addition, the recipient mice received a lethal dose (8.0 Gy,72.76 cGy/min) of total body γ irradiation, and injected with donor mouse derived bone marrow cells (1×107/mouse) and spleen lymphocytes (2×106/mouse) in 6-8 hours post irradiation to establish a mouse aGVHD model (n=20). On the day 7 after modeling, the recipient mice were anesthetized and the blood was harvested post eyeball enucleation. The serum was collected by centrifugation. Mouse MSCs were isolated and cultured with the addition of 2%, 5%, and 10% recipient serum from BMT group or aGVHD group respectively. The colony-forming unit-fibroblast（CFU-F) experiment was performed to evaluate the potential effects of serums on the self-renewal ability of MSC. The expression of CD29 and CD105 of MSC was evaluated by immunofluorescence staining. In addition, the expression of self-renewal-related genes including Oct-4, Sox-2, and Nanog in MSC was detected by real-time fluorescence quantitative PCR（RT-qPCR). RESULTS: We successfully established an in vitro cell model that could mimic the bone marrow microenvironment damage of the mouse with aGVHD. CFU-F assay showed that, on day 7 after the culture, compared with the BMT group, MSC colony formation ability of aGVHD serum concentrations groups of 2% and 5% was significantly reduced （P < 0．05）; after the culture, at day 14, compared with the BMT group, MSC colony formation ability in different aGVHD serum concentration was significantly reduced （P < 0．05）. The immunofluorescence staining showed that, compared with the BMT group, the proportion of MSC surface molecules CD29+ and CD105+ cells was significantly dereased in the aGVHD serum concentration group (P < 0.05), the most significant difference was at a serum concentration of 10% （P < 0．001, P < 0.01）. The results of RT-qPCR detection showed that the expression of the MSC self-renewal-related genes Oct-4, Sox-2, and Nanog was decreased, the most significant difference was observed at an aGVHD serum concentration of 10% （P < 0.01,P < 0．001,P < 0．001）. CONCLUSION: By co-culturing different concentrations of mouse aGVHD serum and mouse MSC, we found that the addition of mouse aGVHD serum at different concentrations impaired the MSC self-renewal ability, which providing a new tool for the field of aGVHD bone marrow microenvironment damage.

Selenium in the treatment of mild-to-moderate Graves' orbitopathy: a 5-year prospective controlled cohort study.

PURPOSE: Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease. However, limited studies have investigated the actual efficacy of selenium in GO therapy. This longitudinal study explored the effect of selenium on QOL and prognosis of patients with mild-to-moderate GO. METHODS: We conducted a 5-year prospective controlled cohort clinical trial to determine the effect of selenium on 74 patients with mild-to-moderate GO. Patients received selenium yeast or placebo orally for 6 months and were followed up at 6 months and at 5 years by biochemical examination, ophthalmologist evaluation and QOL questionnaire to assess oculopathy and QOL. RESULTS: (1) During a follow-up period of 3-6 months, in the selenium group, the symptoms of tearing, grittiness and conjunctival congestion improved (P < 0.01); clinical activity scores and total GO-QOL scores increased relative to baseline (P < 0.01); TRAb was decreased at the 6-month evaluation (P = 0.003); and patients treated with selenium had a higher rate of improvement and a lower rate of worsening than patients treated with placebo (P < 0.05). (2) Exploratory evaluations at 6 months after drug withdrawal confirmed the earlier results; further changes included alleviation of blurred vision and double vision symptoms in the selenium group (P < 0.01). (3) At the 5-year follow-up, compared with baseline, proptosis, clinical activity scores, TRAb level and total GO-QOL scores in both the selenium and placebo groups were significantly improved (P < 0.01). CONCLUSION: Six months of selenium supplementation may effectively change the early course of mild-to-moderate GO, but this regimen makes no difference in long-term outcomes.

Percutaneous nephrolithotomy guided by 5G-powered robot-assisted teleultrasound diagnosis system: first clinical experience with a novel tele-assistance approach (IDEAL stage 1).

BACKGROUND: To demonstrate the technical feasibility of percutaneous nephrolithotomy (PCNL) guided by 5G-powered robot-assisted teleultrasound diagnosis system (RTDS) in a complex kidney-stone (CKS) cohort and present our preliminary outcomes. PCNL is highly skill-required, which hinders it popularization in primary medical units of remote regions. We designed an innovative tele-assistance approach to make PCNL easy to be operated by inexperienced surgeons. METHODS: This was a prospective proof-of-concept study (IDEAL phase 1) on intraoperative tele-assistance provided by online urological experts via a 5G-powered RTDS. Total 15 CKS patients accepted this technology. Online experts manipulated a simulated probe to assist unskilled local operators by driving a patient-side robot-probe to guide and monitor the steps of access establishment and finding residual stones. RESULTS: Median total delay was 177ms despite one-way network-connecting distance > 5,800 km. No perceptible delay of audio-visual communication, driving robot-arm or dynamic ultrasound images was fed back. Successful tele-assistance was obtained in all cases. The first-puncture access-success rate was 78.6% with a one-session SF rate of 71.3% and without complications of grade III-V. CONCLUSIONS: The current technology based on 5G-powered RTDS can provide high-quality intraoperative tele-assistance, which has preliminarily shown satisfactory outcomes and reliable safety. It will break down a personal competence-based barrier to endow PCNL with more popular utilization. TRIAL REGISTRATION: The study was approved by ethics committee of the Xinjiang Kezhou People's Hospital and ethics committee of the First Affiliated Hospital of Nanjing Medical University and was registered on http://www.chictr.org.cn (ChiCTR2200065849, 16/11/2022).

Orexin receptors in paraventricular nucleus influence sexual behavior via regulating the sympathetic outflow in males.

BACKGROUND: Orexins are hypothalamic neuropeptides associated with various neurophysiological activities such as sleep, arousal, and reward. However, there are few studies investigating the relationships between orexin receptors in the paraventricular nucleus and sexual behaviors. OBJECTIVES: To explore the roles of orexin receptors in the paraventricular nucleus on sexual behaviors and uncover its potential mechanisms in males. MATERIALS AND METHODS: Orexin A, orexin 1 receptor antagonist SB334867, and orexin 2 receptor antagonist TCS-OX2-29 were microinjected into the paraventricular nucleus to investigate the effects of orexin receptors on copulatory behavior testing of C57BL/6 mice. To explore if ejaculation could activate orexin 1 receptor-expressing neurons in the paraventricular nucleus, fluorescence immunohistochemical double staining was utilized. The levels of serum norepinephrine were measured and the lumbar sympathetic nerve activity was recorded to reflect the sympathetic nervous system activity. Moreover, the bulbospongiosus muscle-electromyogram was recorded and analyzed. To test whether perifornical/lateral hypothalamic area orexinergic neurons directly projected to the paraventricular nucleus, virus retrograde tracing technology was utilized. RESULTS: Orexin A significantly enhanced sexual performance by shortening the intromission and ejaculation latencies, and increasing the mount and intromission frequencies, while the opposite outcomes appeared with SB334867. However, TCS-OX2-29 had no significant effects on sexual behaviors. Moreover, orexin A increased lumbar sympathetic nerve activity and the levels of serum norepinephrine, while SB334867 decreased lumbar sympathetic nerve activity and norepinephrine, which caused a significant decrease in sympathetic nervous system outflow. Meanwhile, a robust increase in the bulbospongiosus muscle-electromyogram activity was identified after microinjecting orexin A. Furthermore, cFos immunopositive cells were increased and double stained with orexin 1 receptor-expressing neurons in the mating group. Additionally, the retrograde tracing results demonstrated that orexinergic neurons in the perifornical/lateral hypothalamic area directly projected to the paraventricular nucleus. CONCLUSIONS: Orexin 1 receptor in the paraventricular nucleus could influence the ejaculatory reflex via mediating the sympathetic nervous system activity, which might be of great importance in the treatment of premature ejaculation in the future.

Analysis of adverse drug reactions/events of cancer chemotherapy and the potential mechanism of Danggui Buxue decoction against bone marrow suppression induced by chemotherapy.

Objective: To analyze the clinical characteristics of adverse reactions/events based on chemotherapy in cancer patients, and then explore the potential mechanism of Danggui Buxue Decoction (DBD) against chemotherapy-induced bone marrow suppression (BMS). Methods: Retrospectively collected and evaluated were the clinical data of patients in a hospital who experienced adverse reactions/events brought on by chemotherapeutic medications between 2015 and 2022. We explored the potential mechanism of DBD against BMS using network pharmacology based on the findings of the adverse reactions/events analysis. Results: 151 instances (72.25%) experienced adverse reactions/events from a single chemotherapy medication. Besides, platinum-based medications produced the most unfavorable effects. The study also found that chemotherapy caused the highest number of cases of BMS, including platinum drugs. Consequently, BMS is the most prevalent adverse reaction disease caused by chemotherapy found in this part. According to network pharmacology findings, DBD can prevent BMS primarily involving 1,510 primary targets and 19 key active ingredients. Based on the enrichment analysis, PI3K-AKT, TNF, MAPK, and IL-17 signaling pathways made up the majority of the DBD-resisting BMS pathways. Molecular docking displayed that kaempferol, the major active ingredient of DBD, had the highest binding energy (-10.08 kJ mol-1) with PTGS2 (a key target of BMS). Conclusion: Cancer patients who received chemotherapy had a risk to develop BMS. Regular blood tests should be performed while taking medicine; early discovery and treatment can reduce a patient's risk of experiencing adverse reactions/events. Additionally, this study demonstrated that DBD, through a variety of targets and pathways, may be crucial in avoiding BMS.

Resveratrol inhibits AhR/Notch axis and reverses Th17/Treg imbalance in purpura by activating Foxp3.

Background: Resveratrol has been reported to reverse the imbalance of T helper 17/regulatory T (Th17/Treg) by inhibiting the aryl hydrocarbon receptor pathway to treat immune thrombocytopenia. However, the regulation mechanism of the Notch signaling pathway by resveratrol has not been reported in purpura. This study is aimed to explore the mechanism of resveratrol ultrafine nanoemulsion (Res-mNE) in immune thrombocytopenia. Methods: The immune thrombocytopenia mouse model was constructed to explore the effect of RES-mNE on immune thrombocytopenia. Cluster of differentiation 4 (CD4+) T cells were isolated and treated with different medications. CD4+ T cells were induced to differentiate into Th17 cells and Treg cells. Flow cytometry was used to detect the proportion of Th17 cells and Treg cells. The secretion was measured by the enzyme-linked immunosorbent assay (ELISA). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blot were used to detect the mRNA and protein levels. Results: Th17 cells, IL-17A and IL-22 increased in the immune thrombocytopenia mouse model, and the Treg cells and IL-10 decreased. Res-mNE promoted Treg cell differentiation and IL-10 secretion in CD4+ T cells while inhibiting Th17 cell differentiation and IL-17A and IL-22 levels. The AhR activator 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reversed the effect of Res-mNE. Notch inhibitors reduced the ratio of Th17/Treg differentiation. Res-mNE activated the expression of Foxp3 by mediating AhR/Notch signaling to reverse the imbalance of Th17/Treg differentiation in immune thrombocytopenia. Conclusion: Taken together, our findings demonstrated that RES-mNE inhibited the AhR/Notch axis and reversed Th17/Treg imbalance by activating Foxp3.

[Research progress in prevention and treatment of radiation-induced intestinal injury by traditional Chinese medicine active components].

Radiation-induced intestinal injury(RIII), a common complication of radiotherapy for pelvic malignancies, affects the quality of life and the radiotherapy efficacy for cancer. Currently, the main clinical approaches for the prevention and treatment of RIII include drug therapy, hyperbaric oxygen therapy, and surgical treatment. Among these methods, drug therapy is cost-effective. Traditional Chinese medicine(TCM) containing a variety of active components demonstrates mild side effects and good efficacy in preventing and treating RIII. Studies have proven that TCM active components, such as flavonoids, terpenoids, phenylpropanoids, and alkaloids, can protect the intestine against RIII by inhibiting oxidative stress, regulating the expression of inflammatory cytokines, modulating the mitochondrial apoptosis pathway, adjusting intestinal flora, and suppressing cell apoptosis. These mechanisms can help alleviate the symptoms of RIII. The paper aims to provide a theoretical reference for the discovery of new drugs for the prevention and treatment of RIII by reviewing the literature on TCM active components in the last 10 years.

Construction and evaluation of intrauterine adhesion model in rats by different methods of mechanical injury.

PURPOSE: The study aimed to establish a stable and effective animal model for the experimental study of intrauterine adhesion (IUA) by evaluating various mechanical injury methods. METHODS: A total of 140 female rats were divided into four groups according to the extent and area of endometrial injury: group A (excision area: 2.0 × 0.5 cm2), group B (excision area: 2.0 × 0.25 cm2), group C (endometrial curettage) and group D (sham operation). On the 3rd, 7th, 15th and 30th day after the operation, the tissue samples of each group were collected, and the uterine cavity stenosis and histological changes were recorded by HE and Masson staining. Immunohistochemistry of CD31 was applied to visualize microvessel density (MVD). The pregnancy rate and the number of gestational sacs were used to evaluate the reproductive outcome. RESULTS: The results showed that endometrium injured by small-area endometrial excision or simple curettage could be repaired. The ratio of fibrosis in groups A and B was higher than that in groups C and group D 30 days after modeling (P < 0.001). The number of endometrial glands and MVD in group A was significantly lower than those in groups B, C and D (P < 0.05). The pregnancy rate in group A was 20%, which was lower than that in groups B (33.3%), C (89%) and D (100%) (P < 0.05). CONCLUSION: Full-thickness endometrial excision has a high rate of success in constructing stable and effective IUA models in rats.

Metabolic genes, a potential predictor of prognosis and immunogenicity of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC). Many ccRCCs are diagnosed at an advanced stage due to the lack of early symptoms, with a high mortality rate and a poor prognosis. The occurrence and development of ccRCC are closely related to metabolic disorders. This study aims to explore the relationship between metabolic genes and prognosis, immune microenvironment, and tumor development of ccRCC. Using data from TCGA, GEO, and ArrayExpress, we successfully established a risk model (riskScore) based on 4 metabolic genes (MGs) that can accurately predict the prognosis and immune microenvironment of ccRCCs. In addition, we determined the role of PAFAH2 in suppressing tumor cell proliferation and migration in ccRCC in vitro. Our research may shed new light on ccRCC patients' prognosis and treatment management.

[Establishment and Evaluation of Intestinal Injury Model of Mouse Acute Graft Versus Host Disease Based on An Organoid Technology].

OBJECTIVE: To establish an intestinal organoid model that mimic acute graft versus host disease (aGVHD) caused intestinal injuries by using aGVHD murine model serum and organoid culture system, and explore the changes of aGVHD intestine in vitro by advantage of organoid technology. METHODS: 20-22 g female C57BL/6 mice and 20-22 g female BALB/c mice were used as donors and recipients for bone marrow transplantation, respectively. Within 4-6 h after receiving a lethal dose (8.0 Gy) of γ ray total body irradiation, a total of 0.25 ml of murine derived bone marrow cells (1×107/mice, n=20) and spleen nucleated cells (5×106/mice, n=20) was infused to establish a mouse model of aGVHD (n=20). The aGVHD mice were anesthetized at the 7th day after transplantation, and the veinal blood was harvested by removing the eyeballs, and the serum was collected by centrifugation. The small intestinal crypts of healthy C57BL/6 mice were harvested and cultivated in 3D culture system that maintaining the growth and proliferation of intestinal stem cells in vitro. In our experiment, 5%, 10%, 20% proportions of aGVHD serum were respectively added into the organoid culture system for 3 days. The formation of small intestinal organoids were observed under an inverted microscope and the morphological characteristics of intestinal organoids in each groups were analyzed. For further evaluation, the aGVHD intestinal organoids were harvested and their pathological changes were observed. Combined with HE staining, intestinal organ morphology evaluation was performed. Combined with Alcian Blue staining, the secretion function of aGVHD intestinal organoids was observed. The distribution and changes of Lgr5+ and Clu+ intestinal stem cells in intestinal organoids were analyzed under the conditions of 5%, 10% and 20% serum concentrations by immunohistochemical stainings. RESULTS: The results of HE staining showed that the integrity of intestinal organoids in the 5% concentration serum group was better than that in the 10% and 20% groups. The 5% concentration serum group showed the highest number of organoids, the highest germination rate and the lowest pathological score among experimental groups, while the 20% group exhibited severe morphological destruction and almost no germination was observed, and the pathological score was the highest among all groups(t=3.668, 4.334,5.309,P<0.05). The results of Alican blue staining showed that the secretion function of intestinal organoids in serum culture of aGVHD in the 20% group was weaker than that of the 5% group and 10% of the organoids, and there was almost no goblet cells, and mucus was stainned in the 20% aGVHD serum group. The immunohistochemical results showed that the number of Lgr5+ cells of intestinal organoids in the 5% group was more than that of the intestinal organoids in the 10% aGVHD serum group and 20% aGVHD serum group. Almost no Clu+ cells were observed in the 5% group. The Lgr5+ cells in the 20% group were seriously injuried and can not be observed. The proportion of Clu+ cells in the 20% group significantly increased. CONCLUSION: The concentration of aGVHD serum in the culture system can affect the number and secretion function of intestinal organoids as well as the number of intestinal stem cells in organoids. The higher the serum concentration, the greater the risk of organoid injury, which reveal the characteristics of the formation and functional change of aGVHD intestinal organoids, and provide a novel tool for the study of intestinal injury in aGVHD.

Efficacy and safety of dulaglutide compared with the first-line hypoglycemic drugs in Asian patients with type 2 diabetes: a systematic review and meta-analysis.

To assess the efficacy and safety of dulaglutide in the treatment of Asian type 2 diabetes mellitus (T2DM), along with first-line hypoglycemic drugs. Systematic review and meta-analysis. Cochrane Library, Pubmed, Embase, and www.clinicaltrials.gov databases were searched from inception to September 27, 2022. The studies evaluating adults (≥ 18 years) undergoing dulaglutide (0.75 mg and 1.5 mg) and first-line hypoglycemic drugs were considered. There were only English languages. We used Stata 12.0 software to detect the risk of bias. 4 randomized controlled trials (RCTs), and 1 observational study. Both dulaglutide 0.75 mg dose group and 1.5 mg dose group could significantly reduce HbA1c [Dulaglutide 0.75 mg: WMD = - 0.20, 95% CI (- 0.28, - 0.11), P < 0.0001; Dulaglutide 1.5 mg: WMD = - 0.49, 95% CI (- 0.67, - 0.30), P < 0.0001] in Asian T2DM patients. In reducing fasting blood glucose (FBG) level, there was no significant difference observed in 2 dose groups. The body weight of patients in both dulaglutide dose groups was significantly reduced. In safety, the incidence of adverse events in the dulaglutide 0.75 mg dose group was slightly higher than that in the first-line drug group, but there was no statistically significant difference in the incidence of adverse events between the 1.5 mg dose group and the first-line drug group. Furthermore, the incidences of hypoglycemic events in both groups were higher than that in the first-line drug group. Two doses of dulaglutide showed better efficacy for Asian T2DM patients, but patients should be vigilant about the occurrence of hypoglycemia and gastrointestinal discomfort. However, more number and better quality of RCTs are suggested to confirm long-term safety and efficacy.

METTL14 promotes migration and invasion of choroidal melanoma by targeting RUNX2 mRNA via m6A modification.

The modification of N6-methyladenosine is involved in the progression of various cancers. This study aimed to clarify its regulatory mechanism in the pathogenesis of choroidal melanoma. Expression of methyltransferase-like 14 in choroidal melanoma or normal choroidal tissues was determined by Western blot and immunohistochemistry. The impacts of methyltransferase-like 14 on invasion and migration of choroidal melanoma cells were determined using functional and animal experiments. The interaction between methyltransferase-like 14 and its downstream target was identified by methylated RNA immunoprecipitation and a dual-luciferase reporter assay. Additionally, Wnt/ß-catenin signalling pathway was evaluated by Western blot. Methyltransferase-like 14 was upregulated in choroidal melanoma compared to the normal choroidal tissues. Overexpression or knockdown of methyltransferase-like 14 enhanced or inhibited the invasion and migration of choroidal melanoma cells, respectively, both in vivo and in vitro. Methyltransferase-like 14 directly targeted downstream runt-related transcription factor 2 mRNA, depending on N6-methyladenosine. Additionally, the Wnt/ß-catenin signalling pathway was activated by methyltransferase-like 14 in choroidal melanoma cells. Our study identified a novel RNA regulatory mechanism in which runt-related transcription factor 2 was upregulated by enhanced expression of methyltransferase-like 14 via N6-methyladenosine modification, thus facilitating migration and invasion of choroidal melanoma cells.

The influence of marital status on survival in patients with nasopharyngeal carcinoma: A surveillance, epidemiology, and end results database analysis.

BACKGROUND: To assess the influence of marital status on the survival of patients with nasopharyngeal carcinoma (NPC), we used the Surveillance, Epidemiology, and End Results (SEER) database to analyze 5477 patients who were diagnosed with NPC from 2004 to 2016. METHODS: Kaplan-Meier survival analysis and Cox proportional hazard regression were used to analyze the influence of marital status on cause-specific survival (CSS) and overall survival (OS). Subgroup analyses was used to assess the influence of marital status on CSS based on different factors. RESULTS: For the 5477 patients, 61.5%, 22.4%, and 16.1% were married, single/unmarried, and separated/widowed/divorced, respectively. The separated/widowed/divorced group was more likely to be female (P < .001), had the highest proportion of elderly subjects (P < .001), were mostly Caucasian (P < .001), had pathological grade I/II (P < .001), were likely to undergo surgery (P = .032), and were registered in the northeast, north-central, and south (P < .001) regions. The 5-year CSS rates were 92.6%, 92.4%, and 85.1% in the married, single/unmarried, and separated/widowed/divorced groups, respectively (P < .001), and the 5-year OS rates were 60.7%, 54.6%, and 40.1%, respectively (P < .001). CONCLUSION: Marital status is an independent prognostic factor of NPC. Separated/widowed/divorced patients had a significantly increased risk of NPC-related death (hazard ratio [HR] = 2.180, 95% confidence interval [CI] 1.721-2.757, P < .001) compared to married patients. The single/unmarried (P = .355) group had a CSS similar to that of the unmarried group. Marital status is an independent prognostic factor of survival in NPC patients. Separated/widowed/divorced status increases the risk of NPC mortality.

Investigating the Role of Dahuang in Hepatoma Treatment Using Network Pharmacology, Molecular Docking, and Survival Analysis.

Hepatoma is one of the most common malignant tumors. The incidence rate is high in developing countries, and China has the most significant number of cases. Dahuang is a classic traditional antitumor drug commonly used in China and has also been applied to treat hepatoma. However, the potential mechanism of Dahuang in treating hepatoma is not clear. Therefore, this study is aimed at elucidating the possible molecular mechanism and key targets of Dahuang using methods of network pharmacology, molecular docking, and survival analysis. Firstly, the active ingredients and key targets of Dahuang were analyzed through public databases, and then the drug-ingredient-target-disease network diagram of Dahuang against hepatoma was constructed. Five main active components and five core targets were determined according to the enrichment degree. Enrichment analysis demonstrated that Dahuang treated hepatoma through the multiple pathways in cancer. Additionally, molecular docking predicted that aloe-emodin and PIK3CG depicted the best binding energy. Survival analysis indicated that a high/ESR1 gene expression had a relatively good prognosis for patients with hepatoma (p < 0.05). In conclusion, the current study results demonstrated that Dahuang could treat hepatoma through a variety of active ingredients, targets, and multiantitumor pathways. Moreover, it effectively improved the prognosis of hepatoma patients. ESR1 is the potential key gene that is beneficial for the survival of hepatoma patients. Also, aloe-emodin and beta-sitosterol are the two main active crucial ingredients for hepatoma treatment. The study also provided some functional bases and references for the development of new drugs, target mining, and experimental animal research of hepatoma in the future.

Effectiveness and Safety of Rifaximin-Containing Regimens for Helicobacter pylori Eradication: Systematic Review - Are They Potential Eradication Regimens?

Background: Rifaximin, a rifamycin antibiotic, is widely used to treat infectious diarrhea but not commonly used in H. pylori eradication. With its potential advantages of the agent, some studies were conducted on this topic. The aim of this study is to assess effectiveness and safety of rifaximin-containing regimens and to evaluate whether they are alternative choices for H. pylori eradication. Methods: Scientific databases including PubMed, EMbase and Cochrane Library were used to identify clinical trials on rifaximin-containing regimens published from January 2000 to October 2021. Review Manager 5.4 and STATA12 were adopted for the systematic review. Results: In this study, totally 1025 patients were included from 3 randomized controlled and 9 single-arm studies. It showed that the differences in effectiveness and safety between rifaximin-containing and first-line regimens were not statistically significant in randomized controlled trials. However, the results of the single-arm trials indicated that the eradication and adverse drug reaction rate varied suggesting data instability (r=38.1%-85.4%, r ADR 0.00-67.5% by ITT analysis). Among them, the eradication rate of pediatric patients (r=85.4% by ITT analysis) was higher than that of adult patients (r=38.1-74.5% by ITT analysis). Meanwhile, in all adult subgroups (triple or quadruple, with or without amoxicillin, different duration and rifaximin dose), the results did not show sufficient effectiveness as all the eradication rates did not meet the minimum ideal or ideal target. Conclusion: Taken together, rifaximin-containing regimens should not be recommended for H. pylori eradication as they cannot achieve the eradication rate desired.

Infusion of haploidentical HSCs combined with allogenic MSCs for the treatment of ALL patients.

Although haploidentical stem cell transplantation (haplo-HSCT) offers almost all acute lymphoblastic leukaemia (ALL) patients an opportunity for immediate transplantation, it exhibits a higher incidence of graft failure and graft versus host disease (GVHD). Mesenchymal stem cells (MSCs) are characterised by their haematopoiesis-promoting and immunomodulatory capacity. Thus, we designed a combination of haplo-HSCT and MSCs for ALL patients. ALL patients (n = 110) were given haploidentical HSCs combined with allogenic MSCs, and ALL patients without MSC infusion (n = 56) were included as controls. The 100-day cumulative incidences of grade ≥2 acute GVHD (aGVHD) and grade ≥3 aGVHD were 40.00% and 9.09% compared to 42.32% (P = 0.79) and 22.79% (P = 0.03) in patients without MSC infusion, respectively. The 3-year cumulative incidences of chronic GVHD (cGVHD) and extensive cGVHD were 22.27% and 10.27% compared to 32.14% (P = 0.19) and 22.21% (P = 0.04) in patients without MSC infusion, respectively. No significant differences in the 3-year relapse incidence, nonrelapse mortality, leukaemia-free survival or overall survival in groups with and without MSC cotransplantation were observed. Multivariate analysis showed that MSC infusion contributed to a lower risk of developing extensive cGVHD. Our data suggested that haplo-HSCT combined with MSCs may provide an effective and safe treatment for ALL patients.

Xpert MTB/RIF Improves the Prognosis of Multidrug-Resistant Tuberculosis Patients Through Faster Diagnosis and Earlier Targeted Treatment: A Prospective Cohort Study.

Objective: To evaluate the effectiveness of Xpert MTB/RIF in patients with multidrug-resistant tuberculosis (MDR-TB). Methods: Seventy-five patients with MDR-TB were enrolled in this prospective cohort study and were divided into two groups. The observation group were given standardized anti-MDR-TB treatment regimen (6ZAmLfxPtoCs/18ZLfxPtoCs) immediately when they had two positive sputum Xpert MTB/RIF results of RIF resistance. The control group were not given standardized anti-MDR-TB regimen until culture-based drug-susceptibility testing suggested MDR-TB. Treatment effect index, foci absorption, conversion of sputum, treatment outcomes, and adverse reactions were observed. Fisher's exact test and chi-square test were used to compare the differences between groups. Results: Treatment effect index of the observation group significantly out-performed the control group (24/34, 70.6% vs. 17/38, 44.7%, p = 0.027). At the 6th month of treatment course, observation group achieved significantly higher conversion (28/34, 82.3% vs. 23/38, 60.5%, p = 0.042). The foci absorption, cavity change, conversion at the 24th month of course, or treatment outcome between two groups were not statistically different. Conclusion: Xpert MTB/RIF helps MDR-TB patients to start rational treatment regimen earlier and reach earlier sputum conversion.

[Study on Thalassemia in Han Population in Sanya of Hainan Province].

OBJECTIVE: To study the distribution characteristics of thalassemia genotype in Han Population in Sanya of Hainan Province. METHODS: Gap PCR and reverse dot hybridization were used to detect and analyze the thalassemia gene in 572 suspected thalassemia carriers of Han Population in Sanya. RESULTS: Among the 572 Han Population in Sanya, 271 cases of thalassemia gene abnormality were detected, among which 161 cases were founded to be carriers of α-thalassemia gene. A total of 9 genotypes were detected, in the following order of the detection rate was －－SEA/αα，－α3.7/αα，－α4.2/αα，－－SEA/－α3.7，－－SEA/－α4.2，－α4.2/－α4.2，－α3.7/－α4.2，－α3.7/－α3.7，－－SEA/－－SEA. Among them, the deletion type (－－SEA/αα) in southeast Asia was the most common, accounting for 66 cases. 99 cases of ß-thalassemia were detected, there were 7 genotypes, all of which were heterozygous. The order of the detection rate was CD41-42/ßN, IVS-II-654/ßN, CD17/ßN, CD71-72/ßN, -28/ßN, －29/ßN, CD27-28/ßN. Among them, CD41-42/ßN was the most common, accounting for 51 cases. In addition, 11 cases of combined α and ß thalassemia were detected. Five kinds of genotypes were checked out, the order of detection rate was －α3.7/αα composite CD41-42/ßN, －－SEA/αα composite IVS-II-654/ßN, －α4.2/－α4.2 composite CD41-42/ßN, －α4.2/αα composite －29/ßN , －－SEA/ －α4.2 composite CD41-42/ßN. CONCLUSION: Han Population in Sanya of Hainan Province is a high-risk population of thalassemia, the genotype characteristics are different from other areas with high incidence of thalassemia in China. The main type of α-thalassemia is the deficiency mutation of southeast Asia, while CD41-42 heterozygous mutation is the main type of ß-thalassemia.