Perioperative complications of using freezing nitrogen ethanol composite to treat bone tumors: Clinical experience from a single center.

BACKGROUND: The cryoablation efficacy of semisolid freezing nitrogen ethanol composite (FNEC) has been demonstrated. We aimed to investigate the feasibility of adjuvant FNEC-assisted cryoablation in different bone cavity types by assessing the perioperative complication rates. METHODS: The medical charts of patients who received intraoperative adjuvant cryoablation using semisolid FNEC for bone tumors from December 2013 to January 2018 were reviewed. The bone cavities were categorized into three types according to liquid spill potential (type 1, able to hold liquid without limb manipulation; type 2, required extensive limb manipulation to retain liquid; type 3, unable to retain liquid). The overall complication rate and the complication rates stratified by bone cavity type were determined. RESULTS: Among the 76 patients, 30.3%, 57.9%, and 11.8% had type 1, 2, and 3 bone cavities, respectively. The mean follow-up time for perioperative complications was 43.5 ± 24.1 days. Five patients experienced complications, including two cases of skin damage, two cases of skin infection, and one case of fracture, yielding an overall perioperative complication rate of 6.4%. All cases of skin damage and skin infection were superficial and manageable by oral antibiotics. The patient with a pathologic fracture recovered well after being treated with open reduction and plate fixation. No neuropraxia was noted within the first few days postsurgery in any patient. The complication rates in type 1, 2, and 3 bone cavities were 13%, 4.6%, and 0%, respectively. CONCLUSION: All bone cavity types had a low incidence of perioperative complications after treatment with adjuvant FNEC-assisted cryoablation. Semisolid FNEC-assisted cryoablation is a feasible alternative to overcome the liquid spill potential in bone cavities resulting from tumor resection and intralesional curettage.

Effects of inhaled low-concentration xenon gas on naltrexone-precipitated withdrawal symptoms in morphine-dependent mice.

BACKGROUND: Opioid withdrawal symptoms (OWS) are highly aversive and prompt unprescribed opioid use, which increases morbidity, mortality, and, among individuals being treated for opioid use disorder (OUD), recurrence. OWS are driven by sympathetic nervous system (SNS) hyperactivity that occurs when blood opioid levels wane. We tested whether brief inhalation of xenon gas, which inhibits SNS activity and is used clinically for anesthesia and diagnostic imaging, attenuates naltrexone-precipitated withdrawal-like signs in morphine-dependent mice. METHODS: Adult CD-1 mice were implanted with morphine sulfate-loaded (60 mg/ml) minipumps and maintained for 6 days to establish morphine dependence. On day 7, mice were given subcutaneous naltrexone (0.3 mg/kg) and placed in a sealed exposure chamber containing either 21% oxygen/balance nitrogen (controls) or 21% oxygen/added xenon peaking at 30%/balance nitrogen. After 10 minutes, mice were transferred to observation chambers and videorecorded for 45 minutes. Videos were scored in a blind manner for morphine withdrawal behaviors. Data were analyzed using 2-way ANOVAs testing for treatment and sex effects. RESULTS AND CONCLUSIONS: Xenon-exposed mice exhibited fewer jumps (P = 0.010) and jumping suppression was detectible within the first 10-minute video segment, but no sex differences were detected. Brief inhalation of low concentration xenon rapidly and substantially attenuated naltrexone-precipitated jumping in morphine-dependent mice, suggesting that it can inhibit OWS. If xenon effects translate to humans with OUD, xenon inhalation may be effective for reducing OWS, unprescribed opioid use, and for easing OUD treatment initiation, which could help lower excess morbidity and mortality associated with OUD.

Ammonia scavenger and glutamine synthetase inhibitors cocktail in targeting mTOR/ß-catenin and MMP-14 for nitrogen homeostasis and liver cancer.

The glutamine synthetase (GS) facilitates cancer cell growth by catalyzing de novo glutamine synthesis. This enzyme removes ammonia waste from the liver following the urea cycle. Since cancer development is associated with dysregulated urea cycles, there has been no investigation of GS's role in ammonia clearance. Here, we demonstrate that, although GS expression is increased in the setting of ß-catenin oncogenic activation, it is insufficient to clear the ammonia waste burden due to the dysregulated urea cycle and may thus be unable to prevent cancer formation. In vivo study, a total of 165 male Swiss albino mice allocated in 11 groups were used, and liver cancer was induced by p-DAB. The activity of GS was evaluated along with the relative expression of mTOR, ß-catenin, MMP-14, and GS genes in liver samples and HepG2 cells using qRT-PCR. Moreover, the cytotoxicity of the NH3 scavenger phenyl acetate (PA) and/or GS-inhibitor L-methionine sulfoximine (MSO) and the migratory potential of cells was assessed by MTT and wound healing assays, respectively. The Swiss target prediction algorithm was used to screen the mentioned compounds for probable targets. The treatment of the HepG2 cell line with PA plus MSO demonstrated strong cytotoxicity. The post-scratch remaining wound area (%) in the untreated HepG2 cells was 2.0%. In contrast, the remaining wound area (%) in the cells treated with PA, MSO, and PA + MSO for 48 h was 61.1, 55.8, and 78.5%, respectively. The combination of the two drugs had the greatest effect, resulting in the greatest decrease in the GS activity, ß-catenin, and mTOR expression. MSO and PA are both capable of suppressing mTOR, a key player in the development of HCC, and MMP-14, a key player in the development of HCC. PA inhibited the MMP-14 enzyme more effectively than MSO, implying that PA might be a better way to target HCC as it inhibited MMP-14 more effectively than MSO. A large number of abnormal hepatocytes (5%) were found to be present in the HCC mice compared to mice in the control group as determined by the histopathological lesions scores. In contrast, PA, MSO, and PA + MSO showed a significant reduction in the hepatic lesions score either when protecting the liver or when treating the liver. The molecular docking study indicated that PA and MSO form a three-dimensional structure with NF-κB and COX-II, blocking their ability to promote cancer and cause gene mutations. PA and MSO could be used to manipulate GS activities to modulate ammonia levels, thus providing a potential treatment for ammonia homeostasis.

Skin thermal recovery following cryotherapy: a comparison of liquid nitrogen and liquid nitrous oxide.

Cryotherapy is a common technique used in the management of superficial skin lesions, with current advice on the correct timing for freeze-thaw cycles based on nonscientific visual skin appearances. We investigated the effect of cryotherapy on thermal thawing times by creating a porcine skin model in a laboratory setting maintained at normal skin temperature and comparing liquid nitrogen and liquid nitrous oxide. Thermal assessment was performed using a thermal camera attached to an iPhone 11Pro® smartphone. Liquid nitrogen reduced skin temperature to -60 °C after 5 s of application, recovering to 0 °C after 70 s. Liquid nitrous oxide reduced skin temperature to -34.8 °C after 5 s but had a faster recovery to 0 °C after only 20 s. Both cryogens required a thawing period of 5 min to recover to normal skin temperature. We therefore suggest that optimum cellular degradation should allow for 5-min freeze-thaw cryotherapy cycles; a slower thawing period than is in current common practice.

Exhaled breath condensate profiles of U.S. Navy divers following prolonged hyperbaric oxygen (HBO) and nitrogen-oxygen (Nitrox) chamber exposures.

Prolonged exposure to hyperbaric hyperoxia can lead to pulmonary oxygen toxicity (PO2tox). PO2tox is a mission limiting factor for special operations forces divers using closed-circuit rebreathing apparatus and a potential side effect for patients undergoing hyperbaric oxygen (HBO) treatment. In this study, we aim to determine if there is a specific breath profile of compounds in exhaled breath condensate (EBC) that is indicative of the early stages of pulmonary hyperoxic stress/PO2tox. Using a double-blind, randomized 'sham' controlled, cross-over design 14 U.S. Navy trained diver volunteers breathed two different gas mixtures at an ambient pressure of 2 ATA (33 fsw, 10 msw) for 6.5 h. One test gas consisted of 100% O2(HBO) and the other was a gas mixture containing 30.6% O2with the balance N2(Nitrox). The high O2stress dive (HBO) and low O2stress dive (Nitrox) were separated by at least seven days and were conducted dry and at rest inside a hyperbaric chamber. EBC samples were taken immediately before and after each dive and subsequently underwent a targeted and untargeted metabolomics analysis using liquid chromatography coupled to mass spectrometry (LC-MS). Following the HBO dive, 10 out of 14 subjects reported symptoms of the early stages of PO2tox and one subject terminated the dive early due to severe symptoms of PO2tox. No symptoms of PO2tox were reported following the nitrox dive. A partial least-squares discriminant analysis of the normalized (relative to pre-dive) untargeted data gave good classification abilities between the HBO and nitrox EBC with an AUC of 0.99 (±2%) and sensitivity and specificity of 0.93 (±10%) and 0.94 (±10%), respectively. The resulting classifications identified specific biomarkers that included human metabolites and lipids and their derivatives from different metabolic pathways that may explain metabolomic changes resulting from prolonged HBO exposure.

Rosiglitazone Alleviates Contrast-Induced Acute Kidney Injury in Rats via the PPARγ/NLRP3 Signaling Pathway.

Background: This study investigated the effect and mechanism of rosiglitazone on a rat model with contrast-induced acute kidney injury (CI-AKI). Materials and Methods: The CI-AKI rat model was established from Sprague Dawley rats by furosemide injection (10 ml/kg) to the caudal vein followed by iohexol (11.7 ml/kg). The experimental grouping was randomly allocated into control, model, rosiglitazone, and T0070907 groups. Blood samples were collected from the abdominal aorta. Serum creatinine, urea nitrogen, MDA, and SOD contents were detected by biochemical analysis. TNF-α and IL-10 expression was detected by ELISA. Urine creatinine and urine protein were measured following 24-h urine biochemistry testing. Cell pathology and apoptosis were detected by H&E and TUNEL staining, respectively. PPARγ, NLRP3, eNOS, and caspase-3 mRNA expression were detected by qPCR. Caspase-3 and NLRP3 expression were detected by immunohistochemistry. Results: The CI-AKI rat model was successfully established because the results showed that compared with control, serum creatinine, urea nitrogen, MDA, SOD, TNF-α, and IL-10, urine creatinine and urine protein levels were significantly increased in the model group, indicating AKI, but was significantly decreased with rosiglitazone treatment, indicating recovery from injury, while opposite results were obtained with SOD. Apoptosis rate was significantly increased in the model group and significantly decreased with rosiglitazone treatment. NLRP3 and eNOS increased significantly in the model group and decreased significantly with rosiglitazone treatment, while opposite results were obtained with PPARγ. NLRP3 and caspase-3 protein expression was significantly increased in the model group and significantly decreased with rosiglitazone treatment. Conclusion: Rosiglitazone could alleviate acute renal injury in the CI-AKI rat model by regulating the PPARγ/NLRP3 signaling pathway and should be further investigated as a potential treatment in clinical studies.

Effects of Atmospheric Pressure Plasma in the Treatment of Experimental Periodontitis in Beagle Dogs.

OBJECTIVE: The specific objective of this study was to evaluate the effects of atmospheric pressure plasma (APP) in the treatment of experimental periodontitis in Beagle dogs. METHODS: The APP jet was diagnosed using optical emission spectroscopy and laser-induced fluorescence spectroscopy. Six Beagles received stainless steel ligatures to establish experimental periodontitis model. The teeth in the control group were subjected to conventional root surface debridement (RSD) and chlorhexidine irrigation. The APP group also started with RSD and was then subjected to plasma irradiation. Clinical analyses including plaque index, modified sulcus bleeding index, pocket depth and attachment loss (AL), as well as cone-beam computed tomography (CBCT) analysis, were performed at baseline, 4th week, 8th week and 12th week after treatment. RESULTS: The results showed that typical reactive oxygen and nitrogen species were found in the full spectrum and the gas temperature of APP was close to room temperature. The highest concentrations of hydroxide and oxygen were obtained at 5 mm away from the nozzle. In both groups, all values in clinical examinations were significantly lower (P<0.05) at 12th week after treatment than those at baseline. At the 12th week, the AL in clinical examinations and the bone loss in CBCT images in the APP group were significantly lower than those in the control group (P<0.05). The hematoxylin-eosin staining showed more renascent alveolar bone in the APP group than in the control group. CONCLUSION: These findings suggested that APP has profound potential for use as an adjunct approach for periodontitis treatment.

Combinatorial approaches of nanotherapeutics for inflammatory pathway targeted therapy of prostate cancer.

Prostate cancer (PC) is the most prevalent male urogenital cancer worldwide. PC patients presenting an advanced or metastatic cancer succumb to the disease, even after therapeutic interventions including radiotherapy, surgery, androgen deprivation therapy (ADT), and chemotherapy. One of the hallmarks of PC is evading immune surveillance and chronic inflammation, which is a major challenge towards designing effective therapeutic formulations against PC. Chronic inflammation in PC is often characterized by tumor microenvironment alterations, epithelial-mesenchymal transition and extracellular matrix modifications. The inflammatory events are modulated by reactive nitrogen and oxygen species, inflammatory cytokines and chemokines. Major signaling pathways in PC includes androgen receptor, PI3K and NF-κB pathways and targeting these inter-linked pathways poses a major therapeutic challenge. Notably, many conventional treatments are clinically unsuccessful, due to lack of targetability and poor bioavailability of the therapeutics, untoward toxicity and multidrug resistance. The past decade witnessed an advancement of nanotechnology as an excellent therapeutic paradigm for PC therapy. Modern nanovectorization strategies such as stimuli-responsive and active PC targeting carriers offer controlled release patterns and superior anti-cancer effects. The current review initially describes the classification, inflammatory triggers and major inflammatory pathways of PC, various PC treatment strategies and their limitations. Subsequently, recent advancement in combinatorial nanotherapeutic approaches, which target PC inflammatory pathways, and the mechanism of action are discussed. Besides, the current clinical status and prospects of PC homing nanovectorization, and major challenges to be addressed towards the advancement PC therapy are also addressed.

Cost-utility study of home-based cryotherapy device for wart treatment: a randomized, controlled, and investigator-blinded trial.

BACKGROUND: Cryotherapy is typically performed by physicians. No cost-utility studies of home-based cryotherapy have been reported. OBJECTIVES: To study the cost utility of home-based cryotherapy devices and in-hospital liquid nitrogen therapy for cutaneous warts. MATERIALS AND METHODS: This randomized, controlled, investigator-blinded trial was carried out on patients with cutaneous warts. Participants were randomly assigned to two groups: home-based cryotherapy and in-hospital liquid nitrogen therapy. Clinical examinations were conducted at baseline and monthly until cure, and outcomes (cure rate, side effects, total costs, and quality of life) were compared. A cost-utility analysis was performed. RESULTS: Nineteen of 22 patients completed the treatment and were analyzed. The efficacy of home-based cryotherapy and in-hospital therapy was 72.8% and 64.3%, respectively. Side effects (pain, redness, and burning) were observed. The mean numbers of medical visits were 2.83 for home-based therapy and 3.30 for in-hospital therapy. The total costs for home-based therapy and the in-hospital therapy were US $76.03 and $100.45, respectively. The home-based therapy had 0.2297 quality-adjusted life years, slightly higher than the corresponding value of 0.2254 for in-hospital therapy. CONCLUSIONS: Home-based cryotherapy devices are a cost-saving strategy with similar efficacy to in-hospital liquid nitrogen therapy.

The Nitrogen Mustards.

The nitrogen mustards are powerful cytotoxic and lymphoablative agents and have been used for more than 60 years. They are employed in the treatment of cancers, sarcomas, and hematologic malignancies. Cyclophosphamide, the most versatile of the nitrogen mustards, also has a place in stem cell transplantation and the therapy of autoimmune diseases. Adverse effects caused by the nitrogen mustards on the central nervous system, kidney, heart, bladder, and gonads remain important issues. Advances in analytical techniques have facilitated the investigation of the pharmacokinetics of the nitrogen mustards, especially the oxazaphosphorines, which are prodrugs requiring metabolic activation. Enzymes involved in the metabolism of cyclophosphamide and ifosfamide are very polymorphic, but a greater understanding of the pharmacogenomic influences on their activity has not yet translated into a personalized medicine approach. In addition to damaging DNA, the nitrogen mustards can act through other mechanisms, such as antiangiogenesis and immunomodulation. The immunomodulatory properties of cyclophosphamide are an area of current exploration. In particular, cyclophosphamide decreases the number and activity of regulatory T cells, and the interaction between cyclophosphamide and the intestinal microbiome is now recognized as an important factor. New derivatives of the nitrogen mustards continue to be assessed. Oxazaphosphorine analogs have been synthesized in attempts to both improve efficacy and reduce toxicity, with varying degrees of success. Combinations of the nitrogen mustards with monoclonal antibodies and small-molecule targeted agents are being evaluated. SIGNIFICANCE STATEMENT: The nitrogen mustards are important, well-established therapeutic agents that are used to treat a variety of diseases. Their role is continuing to evolve.

Protective mechanism of traditional Chinese medicine guizhi fuling pills against carbon tetrachloride-induced kidney damage is through inhibiting oxidative stress, inflammation and regulating the intestinal flora.

BACKGROUND: Chemical or drug-induced kidney damage has been recognized as a critical cause of kidney failure. The oxidative stress, inflammation, and imbalance of intestinal flora caused by carbon tetrachloride (CCl4) play a fundamental role in chronic kidney damage. Guizhi Fuling pills (GZFL) is a traditional formula consisting of five traditional Chinese medicinal herbs, which can promote blood circulation and improve kidney function. The underlying mechanisms of GZFL improving kidney damage are not fully understood yet. AIM: The current study aimed to explore the effects of GZFL on CCl4-induced kidney damage and intestinal microbiota in mice. METHODS: Male ICR mice were intraperitoneally administered with 20% CCl4 (mixed in a ratio of 1:4 in soybean oil) twice a week, for 4 weeks to induce kidney damage. Creatinine (CRE), urea nitrogen, antioxidant enzymes, and inflammatory cytokines were measured and the histology of the kidney, jejunum, and colon examination to assess kidney and intestinal damage. The expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) family members, nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in kidney tissues, and the tight junction proteins in colonic tissues were detected by Western blot. The gut microbiota was analyzed through 16S rRNA gene sequencing. RESULTS: GZFL treatment decreased the serum CRE and urea nitrogen levels. Moreover, GZFL reduced the levels of pro-inflammatory cytokines and increased antioxidant enzyme activities in kidney and colonic tissues. GZFL improved the kidney, jejunum, and colon histology. Furthermore, GZFL inhibited the expressions of NLRP3, ASC, and cleaved-Caspase-1, while Nrf2, HO-1, NQO1, GCLM, and tight junction proteins were increased. The dysbiosis of intestinal microbiota improved after GZFL treatment. CONCLUSIONS: This study showed that GZFL could improve kidney damage, which might be mainly via the integrated regulations of the Nrf2 pathway, NLRP3 inflammasome, and composition of intestinal microbiota.

Ascorbic acid and hydrocortisone synergistically inhibit septic organ injury via improving oxidative stress and inhibiting inflammation.

BACKGROUND: The current study aimed to investigate the effect of the combination of ascorbic acid (AscA) and hydrocortisone (Hyd) on septic organ injury and its potential mechanism. METHOD: Sepsis was induced in mice by a single intraperitoneal injection of lipopolysaccharides. RESULTS: AscA and Hyd combined showed more effective protection of the injured liver and kidney in septic mice by decreasing alanine aminotransferase, aspartate aminotransferase, serum urea nitrogen, and serum creatinine and ameliorating pathological manifestations than Hyd or AscA alone. AscA showed a mild inhibitory effect on the secretion of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)). However, Hyd showed a weak regulatory effect on septic oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)). However, the combination of AscA and Hyd showed a more powerful inhibitory effect on the septic inflammatory response and oxidative stress than Hyd or AscA alone by decreasing TNF-α, IL-1ß, and IL-6 and regulating MDA, SOD, and GSH. In an in vitro study, cotreatment of RAW 264.7 macrophages with Hyd and AscA sharply reduced reactive oxygen species (ROS) generation and synergistically inhibited TNF-α, IL-1ß, and IL-6 secretion, which could be abolished by additional stimulation with the ROS donor 3-nitropropionic acid (3-NP). As expected, cotreatment of macrophages with Hyd and AscA synergistically inhibited the activation of p38 MAPK and p-p65, and the effect could be reversed by additional stimulation with 3-NP. CONCLUSIONS: AscA and Hyd synergistically protect the kidney and liver from injury by inhibiting the inflammatory response and oxidative stress. The powerful inhibitory effects of AscA on oxidative stress contribute to the synergistic anti-inflammatory action.

Outcomes of Radiofrequency Ablation Compared to Liquid Nitrogen Spray Cryotherapy for the Eradication of Dysplasia in Barrett's Esophagus.

INTRODUCTION: Current guidelines recommend endoscopic eradication therapy (EET) for Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma using either radiofrequency ablation (RFA) or liquid nitrogen spray cryotherapy (LNSC). The aims of this multicenter study are to compare the rate and number of treatment sessions of RFA vs. LNSC to achieve CE-D and CE-IM and assess outcomes for those who switched therapy. METHODS: This is a retrospective cohort study of patients with BE undergoing EET. Demographics, baseline variables, endoscopy details, and histology information were abstracted. RESULTS: One hundred and sixty-two patients were included in this study with 100 patients in the RFA group and 62 patients in the LNSC group. The rate of CE-D and CE-IM did not differ between the RFA group and LNSC group (81% vs. 71.0%, p = 0.14) and (64% vs. 66%, p = 0.78), respectively. The number of sessions to achieve CE-D and CE-IM was higher with LNSC compared to RFA (4.2 vs. 3.2, p = 0.05) and (4.8 vs. 3.5, p = 0.04), respectively. The likelihood of developing recurrent dysplasia was higher among patients who did not achieve CE-IM (12%) compared to those who did achieve CE-IM (4%), p = 0.04. Similar findings were found in those who switched treatment modalities. DISCUSSION: EET is highly effective in eradication of Barrett's associated dysplasia and neoplasia. Both RFA and LNSC achieved similar rates of CE-D and CE-IM although LNSC required more sessions. Also, achievement of CE-IM was associated with less recurrence rates of dysplasia.

Overview of Chemistry and Therapeutic Potential of Non-Nitrogen Heterocyclics as Anticonvulsant Agents.

Epilepsy is a chronic neurological disorder, characterized by the predisposition of unprovoked seizures affecting the neurobiological, psychological, cognitive, economic, and social wellbeing of the patient. As per the 2019 report by World Health Organization, it affects nearly 80% of the population, which comes from middle to low-income countries. It has been suggested that 70% of such cases can be treated effectively if properly diagnosed. It is one of the most common neurological diseases affecting 50 million people globally. Most of the antiepileptic drugs used in clinical practice are only 60-80% effective in controlling the disease. These drugs suffer from serious drawbacks of non-selectivity and toxicity that limit their clinical usefulness. Hence, there is a need to search for safe, potent, and effective anti-epileptic drugs. One of the emerging strategies to discover and develop selective and non-toxic anticonvulsant molecules focuses on the design of non-nitrogen heterocyclic compounds (NNHC). Drugs such as valproic acid, gabapentin, viagabatrin, fluorofelbamate, tiagabine, progabide, pregabalin, gamma amino butyric acid (GABA), etc. do not contain a nitrogen heterocyclic ring but are as effective anticonvulsants as conventional heterocyclic nitrogen compounds. This review covers the various classes of NNHC which have been developed in the recent past as anticonvulsants along with their chemistry, percentage yield, structure-activity relationship and biological activity. The most potent compound in each series has been identified for comparative studies, for further structural modification and to improve the pharmacokinetic profile. Various optimized synthetic pathways and diverse functionalities other than nitrogen-containing rings discussed in the article may help medicinal chemists to design safe and effective anticonvulsant drugs in near future.

Efficacy and Safety of Liquid Nitrogen Cryotherapy for Lichen Simplex Chronicus: A Meta-Analysis.

BACKGROUND: Lichen simplex chronicus (LSC) is characterized by localized lichenification and intense itching. It has been reported that the added use of liquid nitrogen cryotherapy (LNC) for LSC has significant efficacy and notable safety. Therefore, we conducted a meta-analysis based on existing randomized controlled trials (RCTs). METHOD: We searched RCTs on LNC for LSC published up to August 2020 using various databases, including PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure (CNKI), Chinese Biomedicine (CBM), Chinese Scientific Journals Database (VIP), and WanFang Database. Other studies were manually identified using the references cited in reviews. We applied fixed- or random-effects models, and all analyses were performed using Review Manager 5.4 software. RESULTS: Twelve RCTs involving 1,066 participants provided eligible data for the meta-analysis. Based on the clinical effective rate, LNC treatment of LSC (risk ratio, RR 1.25, p = 0.005, I2 = 82%) was superior to controls. Subgroup analysis showed that the use of LNC alone (RR 1.04, I2 = 95%, p > 0.05) is not more effective than other therapies in the treatment of LSC, but the addition of LNC to the existing treatment increases the total clinical efficacy. Furthermore, the combined effect of LNC and topical medication (RR 1.39, I2 = 0%, p < 0.0001) was better than that of LNC and oral medication (RR 1.30, I2 = 0%, p < 0.00001). Greater frequency of LNC treatment did not improve the efficacy (thrice a week: RR 1.39 [1.21, 1.60]; twice a week: RR 1.27; once every 2 weeks: RR 1.32). Data from 6 RCTs with 508 participants showed no significant difference in AEs (p = 0.31) associated with added LNC treatment. CONCLUSION: The addition of LNC (applying a cotton swab soaked with liquid nitrogen to wipe the lesion for approximately 10 s each time) to topical ointments, is effective and safe in the treatment of LSC. Increasing the treatment frequency of LNC did not necessarily improve the efficacy.

Efectos terapéuticos de la crioterapia con nitrógeno líquido en lesiones por fotodaño, en la consulta dermatológica / Therapeutic effects of cryotherapy with liquid nitrogen in lesions by photo damage in dermatologic consultation

RESUMEN La crioterapia es el conjunto de procedimientos que utilizan el frío en la terapéutica médica. Emplea diversos sistemas y tiene como resultado la disminución de la temperatura de la piel; produce una destrucción local de tejido de forma eficaz y controlada. El objetivo de este trabajo fue realizar una actualización para exponer los aspectos esenciales sobre formas de empleos, indicaciones, complicaciones y contraindicaciones. Existen varios métodos de aplicación de la crioterapia, que incluyen las técnicas de congelación de spray o aerosol y con aplicadores, el método criosonda, y el uso de termoacoplador. Está indicada en varias entidades, entre las que se encuentran la queratosis seborreica y actínica, lentigos solares, carcinoma basocelular y espinocelular in situ. Las complicaciones más observadas son vesicoampollas, hiperpigmentación e hipopigmentación, y las contraindicaciones comunes son intolerancia al frío, tumores con bordes no delimitados o con pigmentación muy oscura, en localizaciones cerca de los márgenes de los ojos, párpados, mucosas, alas nasales y el conducto auditivo. El dominio de los métodos de aplicación e indicaciones es indispensable para elegir la conducta adecuada; de esta forma se evitan complicaciones y efectos colaterales (AU).

ABSTRACT Cryotherapy is the whole of procedures that use cold in medical therapy. It uses various systems and results in a decrease in skin temperature, leading to a local destruction of tissue in an effective and controlled way. The objective of this work is to make an update to expose the essential aspects on the ways of use, indications, complications and contraindications. There are several cryotherapy application methods that include spray or spray freezing techniques and applicators, the cryoprobe method, and the thermocoupler use. It is indicated in several entities, and among the most frequent are seborrheic and actinic keratosis, solar lentigo, basal cell and squamous cell carcinomas in situ. The most observed complications are vesical blisters, hyperpigmentation and hypopigmentation, and the most common complications are: cold intolerance, tumors with non-delimited borders or very dark pigmentation, located near the margins of the eyes, on eyelids, mucous membranes, nasal wings, and on the ear canal. The mastery of the signs and application methods are essential to choose the appropriate behavior against the disease: side effects and complications are avoided that way (AU).

Novel Nitrogen Containing Steroid Derivatives for Prostate Cancer Treatment.

This mini-review focuses on the investigation of novel nitrogen-containing steroid derivatives that are potentially applicable for prostate cancer treatment. It covers the literature of the last decade, highlighting the structure of new steroid compounds that exhibit significant activity in prostate cancer cells and possess pharmacological potency. New derivatives of known anti-prostate cancer agents: abiraterone and galeterone, new derivatives of androstane and pregnane modified with nitrogen-containing heterocycles, and some related steroid-derived compounds are discussed in the review.

Reconstruction using a frozen autograft for a skull and humeral lesion of synchronous multicentric osteosarcoma after undergoing successful neoadjuvant chemotherapy: a case report and review of the literature.

BACKGROUND: Synchronous multicentric osteosarcoma (SMOS) is a rare disease characterized by simultaneous multicentricity of intraosseous osteosarcoma without visceral involvement. SMOS, including a skull lesion, which occurs relatively rarely, and reconstruction using a frozen autograft after the excision of a lesion of SMOS has been infrequently reported previously. CASE PRESENTATION: We report an 18-year-old girl with SMOS, with lesions located in the left distal femur, right proximal humerus, and left occipital bone. Her major complaint was pain and swelling around the left knee joint. Asymptomatic lesions of the humerus and skull bone were detected on a systemic bone scan. No visceral organ metastasis was observed. A biopsy of the distal femoral lesion revealed osteosarcoma. Based on the histological findings, multiple bone lesions, and absence of visceral lesion, the clinical diagnosis of SMOS was made. After five courses of neoadjuvant chemotherapy with a regimen of doxorubicin and cisplatin, reconstruction using a tumor prosthesis following wide excision of the left distal femur was performed, and total necrosis was histologically observed in the retracted specimen. Following three cycles of adjuvant chemotherapy, tumor excision and reconstruction with a frozen autograft treated with liquid nitrogen was conducted for both lesions of the humerus and skull, rather than tumor prosthesis or synthetics, in order to retain a normal shoulder function, and to obtain a good cosmetic and functional outcome after treatment of the skull lesion. Further adjuvant chemotherapy could not be administered after the completion of the surgical treatment for all lesions because the adverse events due to chemotherapy were observed. At over 5 years after the diagnosis, she remains clinically disease-free. CONCLUSIONS: An early correct diagnosis, the proper management of chemotherapy, and surgical treatment for all lesions are essential for achieving a good clinical outcome, even in SMOS including a skull lesion. By performing reconstruction using a frozen autograft for a proximal humeral lesion and a skull lesion after confirming the good histological efficacy of neoadjuvant chemotherapy for the primary lesion, the excellent function of the shoulder joint and a good cosmetic outcome at the site of the skull lesion was acquired without complications or recurrence.