Plant cell-surface GIPC sphingolipids sense salt to trigger Ca2+ influx.

Salinity is detrimental to plant growth, crop production and food security worldwide. Excess salt triggers increases in cytosolic Ca2+ concentration, which activate Ca2+-binding proteins and upregulate the Na+/H+ antiporter in order to remove Na+. Salt-induced increases in Ca2+ have long been thought to be involved in the detection of salt stress, but the molecular components of the sensing machinery remain unknown. Here, using Ca2+-imaging-based forward genetic screens, we isolated the Arabidopsis thaliana mutant monocation-induced [Ca2+]i increases 1 (moca1), and identified MOCA1 as a glucuronosyltransferase for glycosyl inositol phosphorylceramide (GIPC) sphingolipids in the plasma membrane. MOCA1 is required for salt-induced depolarization of the cell-surface potential, Ca2+ spikes and waves, Na+/H+ antiporter activation, and regulation of growth. Na+ binds to GIPCs to gate Ca2+ influx channels. This salt-sensing mechanism might imply that plasma-membrane lipids are involved in adaption to various environmental salt levels, and could be used to improve salt resistance in crops.

Development and validation of MRI-based scoring models for predicting placental invasiveness in high-risk women for placenta accreta spectrum.

OBJECTIVES: To develop and validate MRI-based scoring models for predicting placenta accreta spectrum (PAS) invasiveness. MATERIALS AND METHODS: This retrospective study comprised a derivation cohort and a validation cohort. The derivation cohort came from a systematic review of published studies evaluating the diagnostic performance of MRI signs for PAS and/or placenta percreta in high-risk women. The significant signs were identified and used to develop prediction models for PAS and placenta percreta. Between 2016 and 2021, consecutive high-risk pregnant women for PAS who underwent placental MRI constituted the validation cohort. Two radiologists independently evaluated the MRI signs. The reference standard was intraoperative and pathologic findings. The predictive ability of MRI-based models was evaluated using the area under the curve (AUC). RESULTS: The derivation cohort included 26 studies involving 2568 women and the validation cohort consisted of 294 women with PAS diagnosed in 258 women (88%). Quantitative meta-analysis revealed that T2-dark bands, placental/uterine bulge, loss of T2 hypointense interface, bladder wall interruption, placental heterogeneity, and abnormal intraplacental vascularity were associated with both PAS and placenta percreta, and myometrial thinning and focal exophytic mass were exclusively associated with PAS. The PAS model was validated with an AUC of 0.90 (95% CI: 0.86, 0.93) for predicting PAS and 0.85 (95% CI: 0.79, 0.90) for adverse peripartum outcome; the placenta percreta model showed an AUC of 0.92 (95% CI: 0.86, 0.98) for predicting placenta percreta. CONCLUSION: MRI-based scoring models established based on quantitative meta-analysis can accurately predict PAS, placenta percreta, and adverse peripartum outcome. CLINICAL RELEVANCE STATEMENT: These proposed MRI-based scoring models could help accurately predict PAS invasiveness and provide evidence-based risk stratification in the management of high-risk pregnant women for PAS. KEY POINTS: • Accurately identifying placenta accreta spectrum (PAS) and assessing its invasiveness depending solely on individual MRI signs remained challenging. • MRI-based scoring models, established through quantitative meta-analysis of multiple MRI signs, offered the potential to predict PAS invasiveness in high-risk pregnant women. • These MRI-based models allowed for evidence-based risk stratification in the management of pregnancies suspected of having PAS.

The Complexity of Neuropathic Pain and Central Sensitization: Exploring Mechanisms and Therapeutic Prospects.

Neuropathic pain is a common pain syndrome, which seriously affects the quality of life of patients. The mechanism of neuropathic pain is complex. Peripheral tissue injury can trigger peripheral sensitization; however, what really plays a key role is the sensitization of the central nervous system. Central sensitization is a key factor in the perception of chronic pain. Central sensitization refers to the increased sensitivity of the central nervous system to pain treatment, which is related to the change of the functional connection mode of the neural network. The current study aims to reveal the basic molecular mechanisms of central sensitization, including the involvement of P2 purine X4 receptor and brain-derived neurotrophic factor. In terms of treatment, although there are drugs and physical therapy, the accuracy of targeting is limited and the efficacy needs to be further improved. Future therapeutic strategies may involve the development of new drugs designed to specifically inhibit the central sensitization process. This article focuses on the effector molecules involved in central sensitization, aiming to elucidate the pathogenesis of neuropathic pain and provide a basis for the development of more effective treatment models.

CT Radiomics to Predict Macrotrabecular-Massive Subtype and Immune Status in Hepatocellular Carcinoma.

Background Macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC) is an aggressive variant associated with angiogenesis and immunosuppressive tumor microenvironment, which is expected to be noninvasively identified using radiomics approaches. Purpose To construct a CT radiomics model to predict the MTM subtype and to investigate the underlying immune infiltration patterns. Materials and Methods This study included five retrospective data sets and one prospective data set from three academic medical centers between January 2015 and December 2021. The preoperative liver contrast-enhanced CT studies of 365 adult patients with resected HCC were evaluated. The Third Xiangya Hospital of Central South University provided the training set and internal test set, while Yueyang Central Hospital and Hunan Cancer Hospital provided the external test sets. Radiomic features were extracted and used to develop a radiomics model with machine learning in the training set, and the performance was verified in the two test sets. The outcomes cohort, including 58 adult patients with advanced HCC undergoing transarterial chemoembolization and antiangiogenic therapy, was used to evaluate the predictive value of the radiomics model for progression-free survival (PFS). Bulk RNA sequencing of tumors from 41 patients in The Cancer Genome Atlas (TCGA) and single-cell RNA sequencing from seven prospectively enrolled participants were used to investigate the radiomics-related immune infiltration patterns. Area under the receiver operating characteristics curve of the radiomics model was calculated, and Cox proportional regression was performed to identify predictors of PFS. Results Among 365 patients (mean age, 55 years ± 10 [SD]; 319 men) used for radiomics modeling, 122 (33%) were confirmed to have the MTM subtype. The radiomics model included 11 radiomic features and showed good performance for predicting the MTM subtype, with AUCs of 0.84, 0.80, and 0.74 in the training set, internal test set, and external test set, respectively. A low radiomics model score relative to the median value in the outcomes cohort was independently associated with PFS (hazard ratio, 0.4; 95% CI: 0.2, 0.8; P = .01). The radiomics model was associated with dysregulated humoral immunity involving B-cell infiltration and immunoglobulin synthesis. Conclusion Accurate prediction of the macrotrabecular-massive subtype in patients with hepatocellular carcinoma was achieved using a CT radiomics model, which was also associated with defective humoral immunity. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Yoon and Kim in this issue.

Intrathecal Injection of Botulinum Toxin Type A has an Analgesic Effect in Male Rats CCI Model by Inhibiting the Activation of Spinal P2X4R.

Purinergic receptor P2X4 (P2X4R) plays an essential role in neuropathic pain. However, the specific mechanism needs to be clarified. Botulinum toxin type A is a neurotoxin produced by Clostridium botulinum type A. This study found that intrathecal injection of botulinum toxin type A produced an excellent analgesic effect in a rat model of chronic constriction sciatic nerve injury and inhibited the activation of P2X4R, microglia, and astrocytes. The administration of a P2X4R activator can up-regulate the expression of P2X4R and eliminate the analgesic effect of intrathecal injection of botulinum toxin type A. In addition, we found that microglia and astrocytes in the spinal cord of rats injected with botulinum toxin type A were reactivated after administration of the P2X4R activator. Our results suggest that intrathecal injection of botulinum toxin type A has an analgesic effect in a rat model of chronic constriction sciatic nerve injury by inhibiting the activation of P2X4R in the spinal cord.

Research progress in functional magnetic resonance imaging assessment of lupus nephritis kidney injury.

Lupus nephritis is one of the most common and severe complications of systemic lupus erythematosus and is also a major predictor of poor prognosis and mortality. Lupus nephritis has the characteristics of insidious onset, complex pathological types, rapid progression of organ damage, and easy recurrence. Currently, kidney damage in lupus nephritis is usually assessed based on urine analysis, renal biopsy, and glomerular filtration rates. However, they all have certain limitations, making it difficult to diagnose lupus nephritis early and assess its severity and progression. With the rapid development of functional magnetic resonance, multiple functional imaging techniques are expected to provide more useful information for the pathophysiological development, early diagnosis, progression, prognosis, and renal function evaluation of lupus nephritis. This article reviews the principle of multiple functional magnetic resonance imaging and the research status of evaluating renal function in lupus nephritis.

Experimental study on three simple tracers for the assessment of extraneous water into sewer systems.

In recent years, three simple tracers (conductivity, turbidity and temperature) have shown their advantages to many other tracers for tracing and assessment of extraneous water (or inflow and infiltration, I/I) into sewer systems due to low detection cost and high monitoring frequency. A better understanding of the error and uncertainty of the three simple tracers on the quantification of I/I will help to improve the reliability and reduce the cost of actual projects. A large-scale experimental model simulating a 36 m long sewer was constructed for conducting extraneous water flow tests including groundwater infiltration, wastewater inflow and hot water inflow under different I/I flow rates and concentrations. The accuracy and uncertainty of the three tracers were estimated, and their correlation with tracer concentration difference before and after extraneous inflow was also analyzed. Experimental results provide guidance for the practical applicability of the three tracers under different I/I conditions.

Machine learning based on clinical characteristics and chest CT quantitative measurements for prediction of adverse clinical outcomes in hospitalized patients with COVID-19.

OBJECTIVES: To develop and validate a machine learning model for the prediction of adverse outcomes in hospitalized patients with COVID-19. METHODS: We included 424 patients with non-severe COVID-19 on admission from January 17, 2020, to February 17, 2020, in the primary cohort of this retrospective multicenter study. The extent of lung involvement was quantified on chest CT images by a deep learning-based framework. The composite endpoint was the occurrence of severe or critical COVID-19 or death during hospitalization. The optimal machine learning classifier and feature subset were selected for model construction. The performance was further tested in an external validation cohort consisting of 98 patients. RESULTS: There was no significant difference in the prevalence of adverse outcomes (8.7% vs. 8.2%, p = 0.858) between the primary and validation cohorts. The machine learning method extreme gradient boosting (XGBoost) and optimal feature subset including lactic dehydrogenase (LDH), presence of comorbidity, CT lesion ratio (lesion%), and hypersensitive cardiac troponin I (hs-cTnI) were selected for model construction. The XGBoost classifier based on the optimal feature subset performed well for the prediction of developing adverse outcomes in the primary and validation cohorts, with AUCs of 0.959 (95% confidence interval [CI]: 0.936-0.976) and 0.953 (95% CI: 0.891-0.986), respectively. Furthermore, the XGBoost classifier also showed clinical usefulness. CONCLUSIONS: We presented a machine learning model that could be effectively used as a predictor of adverse outcomes in hospitalized patients with COVID-19, opening up the possibility for patient stratification and treatment allocation. KEY POINTS: • Developing an individually prognostic model for COVID-19 has the potential to allow efficient allocation of medical resources. • We proposed a deep learning-based framework for accurate lung involvement quantification on chest CT images. • Machine learning based on clinical and CT variables can facilitate the prediction of adverse outcomes of COVID-19.

Recent advances on synthesis and biological activities of aurones.

Aurones are naturally occurring structural isomerides of flavones that have diverse bioactivities including antiviral, antibacterial, antifungal, anti-inflammatory, antitumor, antimalarial, antioxidant, neuropharmacological activities and so on. They constitute an important class of pharmacologically active scaffolds that exhibit multiple biological activities via diverse mechanisms. This review article provides an update on the recent advances (2013-2020.4) in the synthesis and biological activities of these derivatives. In the cases where sufficient information is available, some important structure-activity relationships (SAR) of their biological activities were presented, and on the strength of our expertise in medicinal chemistry and careful analysis of the recent literature, for the potential of aurones as medicinal drugs is proposed.

Design, synthesis and antifungal activity of amide and imine derivatives containing a kakuol moiety.

In continuation of our program to discover new potential antifungal agents, a series of amide and imine derivatives containing a kakuol moiety were synthesized and characterized by the spectroscopic analysis. By using the mycelium growth rate method, the target compounds were evaluated systematically for antifungal activities in vitro against four plant pathogenic fungi, and structure-activity relationships (SAR) were derived. Compounds 7d, 7e, 7h, 7i and 7r showed obvious inhibitory activity against the corresponding tested fungi at 50 µg/mL. Especially, compounds 7e and 7r displayed more potent antifungal activity against B. cinerea than that of thiabendazole (a positive control). Moreover, compound 7e also exhibited good activity against A. alternata with EC50 values of 11.0 µg/mL, and the value was slightly superior to that of thiabendazole (EC50 = 14.9 µg/mL). SAR analysis showed that the ether group was a highly sensitive structural moiety to the activity and the type as well as position of substituents on benzene ring could make some effects on the activity.

Bacillus baekryungensis MS1 regulates the growth, non-specific immune parameters and gut microbiota of the sea cucumber Apostichopus japonicus.

Winter is a high incidence period of skin ulceration syndrome in the sea cucumber Apostichopus japonicus. Disease control during the overwintering of sea cucumber can help increase yield and reduce losses. The purpose of this study was to study the effect of the low temperature-resistant probiotic Bacillus baekryungensis MS1 on the growth and immune parameters of sea cucumbers and preliminarily investigate the molecular mechanism of the effects. A low temperature-resistant bacterium, B. baekryungensis MS1, was isolated from a sea cucumber pond in winter and used for culture experiments. After 10 days of prefeeding, the experiment was divided into the control group (fed with commercial diet) and the MS1 group (fed with diet containing B. baekryungensis MS1 at 107 cfu g-1) for a total of 60 days. The specific growth rate was measured at the end of the culture period to evaluate the growth performance of the sea cucumber. Samples were taken on days 30 and 60 to determine the immune parameters (including superoxide dismutase activity, catalase activity, alkaline phosphatase activity, acid phosphatase activity, nitric oxide synthetase activity, phagocytosis and respiratory burst), aquaculture water microbiota and gut microbiota of the sea cucumber. Finally, transcriptome sequencing and qRT-PCR verification of the two groups of sea cucumbers were performed to study the mechanism of B. baekryungensis MS1 to improve the immunity of the sea cucumber. The results showed that after 60 days of feeding, B. baekryungensis MS1 significantly improved the growth performance and immune enzyme activity and formed a healthier structure of the gut microbiota in the sea cucumber. The challenge test showed that B. baekryungensis MS1 significantly reduced the mortality of sea cucumbers infected with Vibrio splendidus. Transcriptome and gene expression analysis indicated that B. baekryungensis MS1 activated the ubiquitin-mediated proteolysis pathway and inhibited the mTOR signaling pathway to regulate the immunity of the sea cucumber. In summary, the low temperature-resistant bacterium B. baekryungensis MS1 could be applied for the aquiculture of sea cucumber in winter to improve health status and resist pathogenic bacteria such as V. splendidus.

Overexpression of Amyloid Precursor Protein Promotes the Onset of Seborrhoeic Keratosis and is Related to Skin Ageing.

Seborrhoeic keratosis (SK) is an age-related skin disease. Amyloid precursor protein (APP) plays an important role in the pathogenesis of age-related Alzheimer's disease. The aim of this study was to elucidate the expression characteristics of APP in SK tissues (n = 50), and explore whether the production of APP is related to the onset of SK and skin ageing, including ultraviolet (UV)-induced ageing, as observed in normal skin (n = 79). The results of immunohistochemistry, Western blotting and quantitative real-time PCR showed that APP and its downstream products (i.e. amyloid-ß42) were more highly expressed in SK than in paired adjacent normal skin tissues. In contrast, the expression of its key secretase (i.e. ß-secretase1) was generally low. Furthermore, APP expression was higher in UV-exposed than non-exposed skin sites, and expression in the older age group (61-85 years) was greater than that in the younger age group (41-60 years) in SK tissues (p<0.05). APP expression correlated positively with age in epidermis (p<0.05), but not in dermis. These findings suggest that overexpression of APP may promote the onset of SK and is a marker of skin ageing and UV damage. Further research will elucidate whether therapeutic mitigation of increased levels of APP in the skin might delay the onset of SK and skin ageing.

Trialkylamine Derivatives Containing a Triazole Moiety as Promising Ergosterol Biosynthesis Inhibitor: Design, Synthesis, and Antifungal Activity.

As a part of our continuing research on amine derivative antifungal agents, 19 novel target compounds containing 1,2,4-triazole and tertiary amine moieties were designed and synthesized, and their in vitro antifungal activities against six phytopathogenic fungi (Magnaporthe grisea, Alternaria solani, Fusarium solani, Curvularia lunata, A. alternata, F. graminearum) were assayed. All target compounds were elucidated by means of 1H-NMR, 13C-NMR, high resolution (HR)-MS, and IR analysis. The results showed that most of the derivatives exhibited obvious activity against each of the fungi at 50 µg/mL. Among them, compounds 7f, l, and o displayed excellent activity against A. solani with median effective concentration values (EC50) of 2.88, 8.20, and 1.92 µg/mL. 7o in particular was superior to tebuconazole (EC50=2.03 µg/mL), a commercial fungicide. Furthermore, compounds 7j, k, and m also showed good activity against F. graminearum with EC50 values of 11.60, 5.14, and 16.24 µg/mL, and the value of 7k was extremely close to that of tebuconazole (EC50=3.13 µg/mL). The preliminary analysis of the structure-activity relationship (SAR) demonstrated that combination of the active structure of 1,2,4-triazole with the tertiary amine group containing benzene rings effectively increased the antifungal activities. Generally, introducing halogen atoms obviously improved activities against most of the test fungi to varying degrees, while the presence of OMe decreased the activities. Thus, the results strongly indicate that the newly synthesized derivatives should be lead compounds for the development of novel antifungal agents for the effective control of phytopathogenic fungi.

Synthesis and in Vitro Antifungal Activities of Novel Benzamide Derivatives Containing a Triazole Moiety.

The study reported the synthesis and antifungal activities in vitro against six phytopathogenic fungi of 17 novel N-[2-hydroxy-3,3-dimethyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butyl]benzamide derivatives. All the target compounds were synthesized and elucidated by means of MS, high resolution (HR)-MS, IR, (1)H- and (13)C-NMR analysis. The results showed that almost all the derivatives exhibited good activities against each of the tested fungi at the concentration of 50 µg/mL. Among them, 6h displayed excellent activity against Alternaria alternata with the median effective concentration value (EC50) of 1.77 µg/mL, superior to myclobutanil (EC50=6.23 µg/mL), a commercial fungicide with broad-spectrum bioactivities for plant protection and high-efficiency. Compound 6k showed the broadest antifungal spectrum, demonstrating positive activities against the corresponding fungi with EC50 values ranging from 0.98 to 6.71 µg/mL. Furthermore, 6e to 6i revealed good activities against Alternaria solani with EC50 values of 1.90, 4.51, 7.07, 2.00 and 5.44 µg/mL, respectively. The preliminary analysis of structure-activity relationship (SAR) demonstrated that the presence of F or Cl on the benzene ring remarkably improved the activity, while the introduction of 4-OMe or CF3 group decreased the activity in varying degrees. Thus, the present results strongly suggest that N-[2-hydroxy-3,3-dimethyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butyl]benzamide derivatives should be promising candidates for the development of novel antifungal agents in the effective control of phytopathogenic fungi.

Asperaculanes A and B, two sesquiterpenoids from the fungus Aspergillus aculeatus.

Six sesquiterpenoids 1-6, including two new ones, an ent-daucane-type sesquiterpenoid, asperaculane A (1), and a nordaucane one, asperaculane B (2), and four known nordaucane derivatives, aculenes A-D 3-6, together with the known secalonic acid D (7), were isolated from a fermentation culture of the fungus Aspergillus aculeatus. Their structures and absolute configurations were established by analyses of their spectroscopic data, including 1D and 2D-NMR spectra, HR-ESIMS, electronic circular dichroism (ECD) data, and quantum chemical calculations. These metabolites were evaluated for in vitro cytotoxic activity against two cell lines, human cancer cell lines (HeLa) and one normal hamster cell line (CHO).

Cetuximab inhibits colorectal cancer development through inactivating the Wnt/ß-catenin pathway and modulating PLCB3 expression.

Colorectal cancer (CRC) often necessitates cetuximab (an EGFR-targeting monoclonal antibody) for treatment. Despite its clinical utility, the specific operative mechanism of cetuximab remains elusive. This research investigated the influence of PLCB3, a potential CRC oncogene, on cetuximab treatment. We extracted differentially expressed genes from the GSE140973, the overlapping genes combined with 151 Wnt/ß-Catenin signaling pathway-related genes were identified. Then, we conducted bioinformatics analysis to pinpoint the hub gene. Subsequently, we investigated the clinical expression characteristics of this hub gene, through cell experimental, scrutinized the impact of cetuximab and PLCB3 on CRC cellular progression. The study identified 26 overlapping genes. High expression of PLCB3, correlated with poorer prognosis. PLCB3 emerged as a significant oncogene associated with patient prognosis. In vitro tests revealed that cetuximab exerted a cytotoxic effect on CRC cells, with PLCB3 knockdown inhibiting CRC cell progression. Furthermore, cetuximab treatment led to a reduction in both ß-catenin and PLCB3 expression, while simultaneously augmenting E-cadherin expression. These findings revealed PLCB3 promoted cetuximab inhibition on Wnt/ß-catenin signaling. Finally, simultaneous application of cetuximab with a Wnt activator (IM12) and PLCB3 demonstrated inhibited CRC proliferation, migration, and invasion. The study emphasized the pivotal role of PLCB3 in CRC and its potential to enhance the efficacy of cetuximab treatment. Furthermore, cetuximab suppressed Wnt/ß-catenin pathway to modulate PLCB3 expression, thus inhibiting colorectal cancer progression. This study offered fresh perspectives on cetuximab mechanism in CRC.

The role of long non-coding RNA HCG18 in cancer.

The incidence of cancer is increasing worldwide and is becoming the most common cause of death. Identifying new biomarkers for cancer diagnosis and prognosis is important for developing cancer treatment strategies and reducing mortality. Long non-coding RNAs (lncRNAs) are non-coding, single-stranded RNAs that play an important role as oncogenes or tumor suppressors in the occurrence and development of human tumors. Abnormal expression of human leukocyte antigen complex group 18 (HCG18) is observed in many types of cancer, and its imbalance is closely related to cancer progression. HCG18 regulates cell proliferation, invasion, metastasis, and anti-apoptosis through a variety of mechanisms. Therefore, HCG18 is a potential tumor biomarker and therapeutic target. However, the therapeutic significance of HCG18 has not been well studied, and future research may develop new intervention strategies to combat cancer. In this study, we reviewed the biological function, mechanism, and potential clinical significance of HCG18 in various cancers to provide a reference for future research.

Limitations of ALA-PDT as a reliable therapy for AK in clinical practice.

BACKGROUND: Numerous clinical studies have demonstrated the effectiveness of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) in treating actinic keratosis (AK). This therapy has achieved an average lesion clearance rate of approximately 80 % and has also shown to produce satisfactory cosmetic outcomes. However, in our clinical practice, the utilization and adherence to ALA-PDT treatment among AK patients has been lower than anticipated, possibly due to various factors. OBJECTIVE: The objectives of this study are twofold: (1) To analyze the actual therapeutic effects of ALA-PDT treatment on AK lesions in clinical practice; and (2) To identify the factors that hinder acceptance of ALA-PDT therapy among AK patients with large area or multiple lesions situated on the head and face. METHOD: This study included a group of 20 AK patients, comprising 15 females and 5 males, with an age range of 57-87 years. All patients received a complete course of ALA-PDT therapy, consisting of 3-6 treatments. The study analyzed various factors, including the cure rate, recurrence rate, cosmetic effects, and adverse reactions following treatment. To investigate the factors affecting the acceptance of ALA-PDT treatment among AK patients with large or multiple lesions on the head and face, we also examined a separate group of 43 AK patients. This group included individuals who either had incomplete courses of ALA-PDT treatment or declined the therapy for the first time. The factors potentially influencing patients' acceptance of PDT were analyzed based on the outcomes of these investigations. RESULT: Among the 20 patients who completed the full course of ALA-PDT treatment, the cure rate was 95 % (19/20). The recurrence rates at 1 month, 3 months, and 6 months were 0 %, 5 %, and 10 %, respectively. Out of the 19 cured patients, only 2 experienced heavy pigmentation, and no scarring was reported 1-3 months post-treatment. Based on the survey of 43 patients who either had an incomplete course of ALA-PDT treatment or declined the therapy initially, several factors were identified as limiting their choice of PDT therapy. These factors include: (1) Intolerable adverse effects of treatment. (2) Higher treatment cost than expected. (3) Inconvenient transportation. (4) Coexistence of other senile diseases. (5) Unsatisfactory clinical efficacy observed. (6) Inadequate understanding of AK. (7) Lost to follow-up. CONCLUSION: The study concludes that ALA-PDT is a beneficial and aesthetically pleasing treatment for AK patients, particularly those with extensive or multiple lesions on the head and face. However, various factors can impede the selection of ALA-PDT therapy, potentially depriving patients of the most suitable option. The study aims to assist dermatologists and AK patients in considering treatment plans and exploring alternative options. Overall, the findings of this study may provide valuable guidance for improving treatment outcomes and patient satisfaction.

Intrathecal administration of botulinum toxin type a antagonizes neuropathic pain by countering increased vesicular nucleotide transporter expression in the spinal cord of chronic constriction injury of the sciatic nerve rats.

Botulinum toxin type A (BoNT/A) induces direct analgesic effects in neuropathic pain by inhibiting the release of substance P, calcitonin gene-related peptide (CGRP) and glutamate. Vesicular nucleotide transporter (VNUT) was responsible for the storage and release of ATP in vivo, and one of the mechanisms underlying neuropathic pain is VNUT-dependent release of extracellular ATP from dorsal horn neurons. However, the analgesic effect of BoNT/A by affecting the expression of VNUT remained largely unknown. Thus, in this study, we aimed to elucidate the antinociceptive potency and analgesic mechanism of BoNT/A in chronic constriction injury of the sciatic nerve (CCI) induced neuropathic pain. Our results showed that a single intrathecal injection of 0.1 U BoNT/A seven days after CCI surgery produced significant analgesic activity and decreased the expression of VNUT in the spinal cord of CCI rats. Similarly, BoNT/A inhibited the CCI-induced increase in ATP content in the rat spinal cord. Overexpression of VNUT in the spinal cord of CCI-induced rats markedly reversed the antinociceptive effect of BoNT/A. Furthermore, 33 U/mL BoNT/A dramatically reduced the expression of VNUT in pheochromocytoma (PC12) cells but overexpressing SNAP-25 increased VNUT expression in PC12 cells. Our current study is the first to demonstrate that BoNT/A is involved in neuropathic pain by regulating the expression of VNUT in the spinal cord in rats.