Objective:To compare the clinical efficacy and safety of nanomicroneedle- versus ultrasound-mediated delivery of tranexamic acid for the treatment of melasma.Methods:A prospective, randomized, controlled study was conducted. Patients with melasma were collected from the Department of Dermatology, Guangzhou Dermatology Hospital from March 2023 to May 2024, and divided into a nanomicroneedle group (receiving nanomicroneedle-mediated delivery of tranexamic acid) and an ultrasound group (receiving ultrasound-mediated delivery of tranexamic acid) using the random number table method. Both groups underwent the treatment once a week for a total of 8 sessions. At week 12, outcomes including melasma area and severity index (MASI) scores, treatment response rates, VISIA brown spot scores, pain scores, and adverse reactions were evaluated and compared between the two groups. Statistical analyses were carried out using two-independent-sample t test, Mann-Whitney U test, and chi-square test. Results:A total of 80 patients with melasma were included, with 40 in each group. In the nanomicroneedle group, the patients were aged 40.35 ± 7.39 years (range: 25 - 55 years), with the disease duration being 8.45 ± 4.77 months (range: 1 - 16 months) ; in the ultrasound group, the patients were aged 40.25 ± 7.76 years (range: 25 - 55 years), and their disease duration was 10.45 ± 5.07 months (range: 2 - 17 months) ; there were no significant differences in ages or disease duration between the two groups (both P > 0.05). At week 12, both groups demonstrated reduced MASI scores compared to baseline scores, and the MASI scores were significantly lower in the nanomicroneedle group ( M[ Q1, Q3]: 5.80[4.20, 9.35]) than in the ultrasound group (8.65[5.70, 10.80], Z = 2.50, P = 0.012). The overall response rate was significantly higher in the nanomicroneedle group (97.5%, 39/40) than in the ultrasound group (55.0%, 22/40; χ2 = 19.95, P < 0.001). The lateral facial VISIA brown spot scores were also significantly lower in the nanomicroneedle group (left side: 126.18 ± 36.54 points; right side: 138.50 ± 40.76 points) than in the ultrasound group (left side: 142.37 ± 32.40 points; right side: 157.13 ± 39.59 points; t = -2.10, -2.07, P = 0.039, 0.041, respectively). In the nanomicroneedle group, the pain scores were 4.12 ± 1.47 points, and varying severity of adverse reactions such as erythema, edema and dryness occurred after operation, all of which resolved spontaneously within 48 hours. No marked adverse reactions were observed in the ultrasound group. Conclusion:Nanomicroneedle-mediated delivery of tranexamic acid demonstrated superior clinical efficacy and favorable safety profiles compared to the ultrasound-mediated delivery, providing more options for the treatment of melasma.

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Objective:To compare the clinical efficacy and safety of nanomicroneedle- versus ultrasound-mediated delivery of tranexamic acid for the treatment of melasma.Methods:A prospective, randomized, controlled study was conducted. Patients with melasma were collected from the Department of Dermatology, Guangzhou Dermatology Hospital from March 2023 to May 2024, and divided into a nanomicroneedle group (receiving nanomicroneedle-mediated delivery of tranexamic acid) and an ultrasound group (receiving ultrasound-mediated delivery of tranexamic acid) using the random number table method. Both groups underwent the treatment once a week for a total of 8 sessions. At week 12, outcomes including melasma area and severity index (MASI) scores, treatment response rates, VISIA brown spot scores, pain scores, and adverse reactions were evaluated and compared between the two groups. Statistical analyses were carried out using two-independent-sample t test, Mann-Whitney U test, and chi-square test. Results:A total of 80 patients with melasma were included, with 40 in each group. In the nanomicroneedle group, the patients were aged 40.35 ± 7.39 years (range: 25 - 55 years), with the disease duration being 8.45 ± 4.77 months (range: 1 - 16 months) ; in the ultrasound group, the patients were aged 40.25 ± 7.76 years (range: 25 - 55 years), and their disease duration was 10.45 ± 5.07 months (range: 2 - 17 months) ; there were no significant differences in ages or disease duration between the two groups (both P > 0.05). At week 12, both groups demonstrated reduced MASI scores compared to baseline scores, and the MASI scores were significantly lower in the nanomicroneedle group ( M[ Q1, Q3]: 5.80[4.20, 9.35]) than in the ultrasound group (8.65[5.70, 10.80], Z = 2.50, P = 0.012). The overall response rate was significantly higher in the nanomicroneedle group (97.5%, 39/40) than in the ultrasound group (55.0%, 22/40; χ2 = 19.95, P < 0.001). The lateral facial VISIA brown spot scores were also significantly lower in the nanomicroneedle group (left side: 126.18 ± 36.54 points; right side: 138.50 ± 40.76 points) than in the ultrasound group (left side: 142.37 ± 32.40 points; right side: 157.13 ± 39.59 points; t = -2.10, -2.07, P = 0.039, 0.041, respectively). In the nanomicroneedle group, the pain scores were 4.12 ± 1.47 points, and varying severity of adverse reactions such as erythema, edema and dryness occurred after operation, all of which resolved spontaneously within 48 hours. No marked adverse reactions were observed in the ultrasound group. Conclusion:Nanomicroneedle-mediated delivery of tranexamic acid demonstrated superior clinical efficacy and favorable safety profiles compared to the ultrasound-mediated delivery, providing more options for the treatment of melasma.

In the field of rectal cancer treatment, transanal local excision techniques (such as transanal endoscopic microsurgery [TEM] and transanal minimally invasive surgery [TAMIS]) have gradually become an important therapeutic option for patients with rectal cancer at various stages, owing to their minimally invasive characteristics and organ-preserving advantages. For low-risk T1 stage tumors, local excision can achieve radical tumor control while preserving organ function. For some patients with high-risk T1 stage or T2-3 stage rectal cancer, the efficacy of combined chemoradiotherapy and local excision is expected to be comparable to that of radical total mesorectal excision (TME). In patients with advanced rectal cancer who achieve clinical complete response (cCR) after neoadjuvant therapy, local excision can confirm the pathological remission status. However, it is necessary to balance the risk of surgical complications against the potential benefits of organ preservation with the "watch and wait" strategy. Currently, transanal local excision techniques have broad application prospects, and comprehensive assessment of patients' overall condition, implementation of multidisciplinary collaboration, and conduct of long-term follow-up are crucial to ensuring the safety of treatment.

In the field of rectal cancer treatment, transanal local excision techniques (such as transanal endoscopic microsurgery [TEM] and transanal minimally invasive surgery [TAMIS]) have gradually become an important therapeutic option for patients with rectal cancer at various stages, owing to their minimally invasive characteristics and organ-preserving advantages. For low-risk T1 stage tumors, local excision can achieve radical tumor control while preserving organ function. For some patients with high-risk T1 stage or T2-3 stage rectal cancer, the efficacy of combined chemoradiotherapy and local excision is expected to be comparable to that of radical total mesorectal excision (TME). In patients with advanced rectal cancer who achieve clinical complete response (cCR) after neoadjuvant therapy, local excision can confirm the pathological remission status. However, it is necessary to balance the risk of surgical complications against the potential benefits of organ preservation with the "watch and wait" strategy. Currently, transanal local excision techniques have broad application prospects, and comprehensive assessment of patients' overall condition, implementation of multidisciplinary collaboration, and conduct of long-term follow-up are crucial to ensuring the safety of treatment.

OBJECTIVE To analyze the occurrence characteristics and risk factors of adverse drug reactions(ADR)of gemcitabine for injection in national centralized volume-based procurement(hereinafter referred to as"centralized procurement"),and provide reference for clinical safe drug use.METHODS A retrospective study was conducted to collect the relevant case reports of gemcitabine for injection reported to the National Adverse Drug Reaction Monitoring System by Inner Mongolia Autonomous Region from January 2022 to December 2023;basic information of patients,drug use status,patient outcomes,rational drug use and other information were collected,and the occurrence characteristics of ADRs with leukopenia,myelosuppression,neutropenia,thrombocytopenia and liver dysfunction were analyzed.Univariate analysis and multivariate Logistic regression were used to analyze the correlation of gender,age,combination of antitumor drugs,original malignant tumor and drug dose with ADR.RESULTS A total of 315 cases reports(315 patients)of gemcitabine-induced ADR were included in this study,with a male-to-female ratio of 1.42∶1 and age of(61.17±9.13)years.The primary malignant tumor was pancreatic cancer(73 cases,23.17%).Leukopenia,myelosuppression and nausea were the most common ADR,followed by neutropenia,thrombocytopenia,liver dysfunction and so on.The severity grade of ADR was mainly 1-2,and the outcome of most ADR was good.Multivariate Logistic regression analysis showed that combination of antitumor drugs was a risk factor for myelosuppression and neutropenia(RR=2.154,95%CI:1.218-3.807,P=0.008;RR=3.099,95%CI:1.240-7.744,P=0.016);gender(female)was a risk factor for leukopenia and liver dysfunction(RR=0.508,95%CI:0.302-0.853,P=0.010;RR=0.301,95%CI:0.102-0.887,P=0.029).In terms of drug use rationality,there were 143 cases(45.40%)of drug use in accordance with the indications of the label,and 172 cases(54.60%)of off-label drug use.Among them,the primary malignant tumors were bladder cancer,bile duct cancer and ovarian cancer,which ranked the top three off-label drug use.CONCLUSIONS The ADR caused by gemcitabine in Inner Mongolia is mainly in the blood and digestive systems.The severity of ADRs is mainly classified as 1-2 levels,and most ADRs have good outcomes.Gender(female)and combination medication are risk factors for gemcitabine-induced ADR.Appropriate chemotherapy regimen should be selected according to the patient's condition and physical condition,and ADR monitoring in blood and digestive systems should be strengthened during medication of gemcitabine.

Objective To discuss the safety and efficacy of arterial embolization combined with local ablation in the treatment of recurrent and refractory chest wall tumors.Methods The clinical data of 11 patients with chest wall tumor that recurred after surgery and progressed after treatment were retrospectively analyzed.On the basis of the original treatment regimen,DSA-guided arterial embolization and CT-guided local ablation were employed.VAS score of pain relief and postoperative complications were recorded,and the therapeutic efficacy was evaluated Results All the patients were follow up for a median time of 18.5 months.Successful DSA-guided arterial embolization was accomplished in all patients.Seven patients(9 lesions in total)initially received CT-guided radiofrequency ablation(RFA),and tumor reoccurred in 2 patients,who had to receive RFA once more.Four patients(5 lesions in total)initially received CT-guided microwave ablation(MWA),and tumor reoccurred in one patient,who had to receive MWA again.According to mRECIST criteria,the 6-month,12-month and 18-month objective response rates(ORR)were 72.7%(8/11),45.5%(5/11)and 18.2%(2/11)respectively,the 6-month,12-month and 18-month overall survival rates were 81.8%(9/11),63.6%(7/11)and 27.3%(3/11)respectively,with a median survival time of 13.2 months.The postoperative one-month and 3-month VAS scores were(2.42±1.25)points and(1.91±1.24)points respectively,which were strikingly lower than preoperative(6.78±1.13)points,the differences were statistically significant(P＜0.05).After surgery,3 patients developed pleural effusion,which disappeared after puncture and drainage treatment,and 2 patients developed fever,which was improved after symptomatic treatment.One patient died of respiratory failure six months after treatment.Conclusion Arterial embolization combined with local ablation can improve the symptoms of pain and prolong the survival time of patients with chest wall tumors.This combination therapy is less traumatic and clinically safe,and it can be used as an effective treatment for patients with recurrent and refractory chest wall tumors.

This study aims to establish a multiplex TaqMan fluorescence quantitative PCR(qPCR)assay for Pasteurella multocida(P.multocida).Specific primers and fluorescent labeling probes were designed based on the sequences of five podoplanar genes of P.multocida hyaC-hyaD,bcbD,dcbF,ecbJ,and fcbD in the NCBI database.We adjusted the annealing temperature by gradient setting,optimized the primer and probe concentrations by matrix method,constructed standard curves,and performed specificity,sensitivity and reproducibility tests,and finally established mul-tiplexed TaqMan qPCR assays for these five genes.The results showed that the established assay had a good linear relationship between the amplification curves.The sensitivity of this method was high,10-100 times higher than that of ordinary PCR;the specificity was strong,and there was no amplification curve in the DNA detection of eight pathogenic bacteria such as Bacillus,Proteus mirabilis,Staphylococcus aureus,and Rhizoctonia rad iodurans.This assay had a good linear rela-tionship,and the coefficients of variation for Ct values of the inter-and intra-group reproducibility tests were all less than 3％,and the detection rate of this assay was 11.25％higher than the con-ventional PCR assay through the detection of 90 clinical samples.The method established in this study is able to detect P.multocida rapidly and sensitively,which is important for its rapid clinical and laboratory diagnosis.

OBJECTIVE To analyze the use of children's drugs in public medical institutions in the Inner Mongolia Autonomous Region,and provide some reference for the rational use of children's drugs and the improvement of children's drug list in the whole region. METHODS The generic names,specifications,and dosage forms of children's drugs were collected from all levels of public medical institutions in the Inner Mongolia Autonomous Region in 2023. The method of defined daily dose (DDD) and ranking ratio (B/A) were used to explore the frequency of drug use,daily average cost and cost-effectiveness of children's drugs in this region,and the dosage forms,category,and drug use convergence of children's drugs in medical institutions in the whole region. RESULTS In 2023,1751 public medical and health institutions in Inner Mongolia Autonomous Region were equipped with 267 kinds of children's drugs,including 12 drug categories. The main dosage forms were granules,oral solutions,and syrups. The drugs that were frequently used in medical institutions at all levels were mainly antipyretic,analgesic,anti-inflammatory drugs (mostly Chinese patent medicines),and respiratory drugs. The daily average cost of children's drugs with the highest DDDs in tertiary,secondary,and primary public medical institutions was low,and the B/A value of most drugs with higher DDDs was around 1. However,the B/A value of some drugs was high,which may lead to overuse. The drug use convergence between primary public medical institutions and secondary/tertiary public medical institutions was less than 50％. CONCLUSIONS The types of drugs involved in children's drugs in Inner Mongolia Autonomous Region are comprehensive and the social and economic benefits are in good synchronization,but the dosage form is single and there are few special rules and dosage forms for children. The proportions of Chinese patent medicines in primary and secondary public medical institutions are high,and the risk of drug use should be paid attention. The cohesion between children's drugs in primary public medical institutions and higher public medical institutions is slightly poor.

Objective:To investigate the prognostic value of metabolic parameters of 18F-fluorodeoxyglucose ( 18F-FDG) positron emission computed tomography/computed tomography(PET/CT) in advanced non-small cell lung cancer(NSCLC) treated with first-line immune checkpoint inhibitor (ICI) combined with chemotherapy. Methods:A retrospective study was conducted to evaluate patients with advanced NSCLC who underwent baseline PET/CT before treatment at the Affiliated Cancer Hospital of Zhengzhou University from 2019 to 2021. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-offs for metabolic parameters of PET/CT, including total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), and maximum standard uptake value (SUV max). Kaplan-Meier method, Log-rank test, and Cox regression model were used to calculate the overall survival (OS) and the progression-free survival(PFS). Results:A total of 44 patients were enrolled. Univariate analysis showed that the factors influencing PFS were TMTV and the number of metastatic sites ( χ2=4.19, 11.28, P<0.05) and the factors influencing OS were TMTV and TLG ( χ2=14.96, 6.05, P<0.05). Multivariate analysis suggested that number of metastatic sites was an independent prognostic marker for PFS ( P=0.011) and TMTV was an independent prognostic marker for OS ( P=0.038). Conclusions:TMTV is a prognostic indicator of OS while the number of metastatic sites is a prognostic indicator of PFS in advanced NSCLC patients who received first-line ICI combined with chemotherapy, but further prospective studies are needed.