Targeting EFHD2 inhibits interferon-γ signaling and ameliorates non-alcoholic steatohepatitis.

BACKGROUND & AIMS: The precise pathomechanisms underlying the development of non-alcoholic steatohepatitis (NASH, also known as metabolic dysfunction-associated steatohepatitis [MASH]) remain incompletely understood. In this study, we investigated the potential role of EF-hand domain family member D2 (EFHD2), a novel molecule specific to immune cells, in the pathogenesis of NASH. METHODS: Hepatic EFHD2 expression was characterized in patients with NASH and two diet-induced NASH mouse models. Single-cell RNA sequencing (scRNA-seq) and double-immunohistochemistry were employed to explore EFHD2 expression patterns in NASH livers. The effects of global and myeloid-specific EFHD2 deletion on NASH and NASH-related hepatocellular carcinoma were assessed. Molecular mechanisms underlying EFHD2 function were investigated, while chemical and genetic investigations were performed to assess its potential as a therapeutic target. RESULTS: EFHD2 expression was significantly elevated in hepatic macrophages/monocytes in both patients with NASH and mice. Deletion of EFHD2, either globally or specifically in myeloid cells, improved hepatic steatosis, reduced immune cell infiltration, inhibited lipid peroxidation-induced ferroptosis, and attenuated fibrosis in NASH. Additionally, it hindered the development of NASH-related hepatocellular carcinoma. Specifically, deletion of myeloid EFHD2 prevented the replacement of TIM4+ resident Kupffer cells by infiltrated monocytes and reversed the decreases in patrolling monocytes and CD4+/CD8+ T cell ratio in NASH. Mechanistically, our investigation revealed that EFHD2 in myeloid cells interacts with cytosolic YWHAZ (14-3-3ζ), facilitating the translocation of IFNγR2 (interferon-γ receptor-2) onto the plasma membrane. This interaction mediates interferon-γ signaling, which triggers immune and inflammatory responses in macrophages during NASH. Finally, a novel stapled α-helical peptide targeting EFHD2 was shown to be effective in protecting against NASH pathology in mice. CONCLUSION: Our study reveals a pivotal immunomodulatory and inflammatory role of EFHD2 in NASH, underscoring EFHD2 as a promising druggable target for NASH treatment. IMPACT AND IMPLICATIONS: Non-alcoholic steatohepatitis (NASH) represents an advanced stage of non-alcoholic fatty liver disease (NAFLD); however, not all patients with NAFLD progress to NASH. A key challenge is identifying the factors that trigger inflammation, which propels the transition from simple fatty liver to NASH. Our research pinpointed EFHD2 as a pivotal driver of NASH, orchestrating the over-activation of interferon-γ signaling within the liver during NASH progression. A stapled peptide designed to target EFHD2 exhibited therapeutic promise in NASH mice. These findings support the potential of EFHD2 as a therapeutic target in NASH.

Ferroptosis inhibitor liproxstatin-1 alleviates metabolic dysfunction-associated fatty liver disease in mice: potential involvement of PANoptosis.

Ferroptosis is a new form of regulated cell death characterized by excessive iron accumulation and uncontrollable lipid peroxidation. The role of ferroptosis in metabolic dysfunction-associated fatty liver disease (MAFLD) is not fully elucidated. In this study we compared the therapeutic effects of ferroptosis inhibitor liproxstatin-1 (LPT1) and iron chelator deferiprone (DFP) in MAFLD mouse models. This model was established in mice by feeding a high-fat diet with 30% fructose in water (HFHF) for 16 weeks. The mice then received LPT1 (10 mg·kg-1·d-1, ip) or DFP (100 mg·kg-1·d-1, ig) for another 2 weeks. We showed that both LPT1 and DFP treatment blocked the ferroptosis markers ACSL4 and ALOX15 in MAFLD mice. Furthermore, LPT1 treatment significantly reduced the liver levels of triglycerides and cholesterol, lipid peroxidation markers 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA), and ameliorated the expression of lipid synthesis/oxidation genes (Pparα, Scd1, Fasn, Hmgcr and Cpt1a), insulin resistance, mitochondrial ROS content and liver fibrosis. Importantly, LPT1 treatment potently inhibited hepatic apoptosis (Bax/Bcl-xL ratio and TUNEL+ cell number), pyroptosis (cleavages of Caspase-1 and GSDMD) and necroptosis (phosphorylation of MLKL). Moreover, LPT1 treatment markedly inhibited cleavages of PANoptosis-related caspase-8 and caspase-6 in MAFLD mouse liver. In an in vitro MAFLD model, treatment with LPT1 (100 nM) prevented cultured hepatocyte against cell death induced by pro-PANoptosis molecules (TNF-α, LPS and nigericin) upon lipid stress. On the contrary, DFP treatment only mildly attenuated hepatic inflammation but failed to alleviate lipid deposition, insulin resistance, apoptosis, pyroptosis and necroptosis in MAFLD mice. We conclude that ferroptosis inhibitor LPT1 protects against steatosis and steatohepatitis in MAFLD mice, which may involve regulation of PANoptosis, a coordinated cell death pathway that involves apoptosis, pyroptosis and necroptosis. These results suggest a potential link between ferroptosis and PANoptosis.

Exerkine fibronectin type-III domain-containing protein 5/irisin-enriched extracellular vesicles delay vascular ageing by increasing SIRT6 stability.

AIMS: Exercise confers protection against cardiovascular ageing, but the mechanisms remain largely unknown. This study sought to investigate the role of fibronectin type-III domain-containing protein 5 (FNDC5)/irisin, an exercise-associated hormone, in vascular ageing. Moreover, the existence of FNDC5/irisin in circulating extracellular vesicles (EVs) and their biological functions was explored. METHODS AND RESULTS: FNDC5/irisin was reduced in natural ageing, senescence, and angiotensin II (Ang II)-treated conditions. The deletion of FNDC5 shortened lifespan in mice. Additionally, FNDC5 deficiency aggravated vascular stiffness, senescence, oxidative stress, inflammation, and endothelial dysfunction in 24-month-old naturally aged and Ang II-treated mice. Conversely, treatment of recombinant irisin alleviated Ang II-induced vascular stiffness and senescence in mice and vascular smooth muscle cells. FNDC5 was triggered by exercise, while FNDC5 knockout abrogated exercise-induced protection against Ang II-induced vascular stiffness and senescence. Intriguingly, FNDC5 was detected in human and mouse blood-derived EVs, and exercise-induced FNDC5/irisin-enriched EVs showed potent anti-stiffness and anti-senescence effects in vivo and in vitro. Adeno-associated virus-mediated rescue of FNDC5 specifically in muscle but not liver in FNDC5 knockout mice, promoted the release of FNDC5/irisin-enriched EVs into circulation in response to exercise, which ameliorated vascular stiffness, senescence, and inflammation. Mechanistically, irisin activated DnaJb3/Hsp40 chaperone system to stabilize SIRT6 protein in an Hsp70-dependent manner. Finally, plasma irisin concentrations were positively associated with exercise time but negatively associated with arterial stiffness in a proof-of-concept human study. CONCLUSION: FNDC5/irisin-enriched EVs contribute to exercise-induced protection against vascular ageing. These findings indicate that the exerkine FNDC5/irisin may be a potential target for ageing-related vascular comorbidities.

Cavity-Enhanced Atom-Photon Entanglement with Subsecond Lifetime.

A cold atomic ensemble suits well for optical quantum memories, and its entanglement with a single photon forms the building block for quantum networks that give promise for many revolutionary applications. Efficiency and lifetime are among the most important figures of merit for a memory. In this Letter, we report the realization of entanglement between an atomic ensemble and a single photon with subsecond lifetime and high efficiency. We engineer dual control modes in a ring cavity to create entanglement and make use of three-dimensional optical lattice to prolong memory lifetime. The memory efficiency is 38% for 0.1 s storage. We verify the atom-photon entanglement after 1 s storage by testing the Bell inequality with a result of S=2.36±0.14.

Experimental Time-Resolved Interference with Multiple Photons of Different Colors.

Interference of multiple photons via a linear-optical network has profound applications for quantum foundation, quantum metrology, and quantum computation. Particularly, a boson sampling experiment with a moderate number of photons becomes intractable even for the most powerful classical computers. Scaling up from small-scale experiments requires highly indistinguishable single photons, which may be prohibited for many physical systems. Here we report a time-resolved multiphoton interference experiment by using photons not overlapping in their frequency spectra from three atomic-ensemble quantum memories. Time-resolved measurement enables us to observe nonclassical multiphoton correlation landscapes, which agree well with theoretical calculations. Symmetries in the landscapes are identified to reflect symmetries of the optical network. Our experiment can be further extended to realize boson sampling with many photons and plenty of modes, which thus may provide a route towards quantum supremacy with nonidentical photons.

Hong-Ou-Mandel Interference between Two Deterministic Collective Excitations in an Atomic Ensemble.

We demonstrate deterministic generation of two distinct collective excitations in one atomic ensemble, and we realize the Hong-Ou-Mandel interference between them. Using Rydberg blockade we create single collective excitations in two different Zeeman levels, and we use stimulated Raman transitions to perform a beam-splitter operation between the excited atomic modes. By converting the atomic excitations into photons, the two-excitation interference is measured by photon coincidence detection with a visibility of 0.89(6). The Hong-Ou-Mandel interference witnesses an entangled NOON state of the collective atomic excitations, and we demonstrate its two times enhanced sensitivity to a magnetic field compared with a single excitation. Our work implements a minimal instance of boson sampling and paves the way for further multimode and multiexcitation studies with collective excitations of atomic ensembles.

Highly retrievable spin-wave-photon entanglement source.

Entanglement between a single photon and a quantum memory forms the building blocks for a quantum repeater and quantum network. Previous entanglement sources are typically with low retrieval efficiency, which limits future larger-scale applications. Here, we report a source of highly retrievable spin-wave-photon entanglement. Polarization entanglement is created through interaction of a single photon with an ensemble of atoms inside a low-finesse ring cavity. The cavity is engineered to be resonant for dual spin-wave modes, which thus enables efficient retrieval of the spin-wave qubit. An intrinsic retrieval efficiency up to 76(4)% has been observed. Such a highly retrievable atom-photon entanglement source will be very useful in future larger-scale quantum repeater and quantum network applications.

Topological spin-orbit-coupled fermions beyond rotating wave approximation.

The realization of spin-orbit-coupled ultracold gases has driven a wide range of research and is typically based on the rotating wave approximation (RWA). By neglecting the counter-rotating terms, RWA characterizes a single near-resonant spin-orbit (SO) coupling in a two-level system. Here, we propose and experimentally realize a new scheme for achieving a pair of two-dimensional (2D) SO couplings for ultracold fermions beyond RWA. This work not only realizes the first anomalous Floquet topological Fermi gas beyond RWA, but also significantly improves the lifetime of the 2D-SO-coupled Fermi gas. Based on pump-probe quench measurements, we observe a deterministic phase relation between two sets of SO couplings, which is characteristic of our beyond-RWA scheme and enables the two SO couplings to be simultaneously tuned to the optimum 2D configurations. We observe intriguing band topology by measuring two-ring band-inversion surfaces, quantitatively consistent with a Floquet topological Fermi gas in the regime of high Chern numbers. Our study can open an avenue to explore exotic SO physics and anomalous topological states based on long-lived SO-coupled ultracold fermions.

Bioactive polyhydroxylated steroids from the Hainan soft coral Sinularia depressa Tixier-Durivault.

Two new steroids, (2ß,3ß,4α,5α,8ß)-4-methylergost-24(28)-ene-2,3,8-triol (1) and (3ß,7α)-24-methyl-7-hydroperoxycholest-5,24(28)-diene-3-ol (2), together with 13 known analogues (3-15) were isolated from the soft coral Sinularia depressa Tixier-Durivault. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. In the bioassay in vitro, compounds 3a, 4, and 14 exhibited potent PTP1B inhibitory activity, being similar as that of positive control oleanolic acid. Compound 14 also displayed a notable neuroprotective activity against both amyloid-ß(25-35)- and serum deprivation-induced injuries in SH-SY5Y cells while compound 11 showed a considerable antibacterial activity against Staphylococcus aureus. Preliminary structure-activity relationships of these steroids were discussed.

(M)- and (P)-bicelaphanol A, dimeric trinorditerpenes with promising neuroprotective activity from Celastrus orbiculatus.

(M)-Bicelaphanol A (1) and (P)-bicelaphanol A (2), two unprecedented dimeric trinorditerpenes existing as atropisomers, together with their monomer celaphanol A (3), were isolated from the root bark of Celastrus orbiculatus. The structures and absolute configurations of 1 and 2 were determined by spectroscopic and single-crystal X-ray diffraction analyses. Compound 1 exhibited a significant in vitro neuroprotective effect against a hydrogen peroxide-induced cell viability decrease in PC12 cells at 1 µM, while compounds 2 and 3 showed such effects at 10 µM.

Ferroptotic stress facilitates smooth muscle cell dedifferentiation in arterial remodelling by disrupting mitochondrial homeostasis.

Smooth muscle cell (SMC) phenotypic switch from a quiescent 'contractile' phenotype to a dedifferentiated and proliferative state underlies the development of cardiovascular diseases (CVDs); however, our understanding of the mechanism is still incomplete. In the present study, we explored the potential role of ferroptosis, a novel nonapoptotic form of cell death, in SMC phenotypic switch and related neointimal formation. We found that ferroptotic stress was triggered in cultured dedifferentiated SMCs and arterial neointimal tissue of wire-injured mice. Moreover, pro-ferroptosis stress was activated in arterial neointimal tissue of clinical patients who underwent carotid endarterectomy. Blockade of ferroptotic stress via administration of a pharmacological inhibitor or by global genetic overexpression of glutathione peroxidase-4 (GPX4), a well-established anti-ferroptosis molecule, delayed SMC phenotype switch and arterial remodelling. Conditional SMC-specific gene delivery of GPX4 using adreno-associated virus in the carotid artery inhibited ferroptosis and prevented neointimal formation. Conversely, ferroptosis stress directly triggered dedifferentiation of SMCs. Transcriptomics analysis demonstrated that inhibition of ferroptotic stress mainly targets the mitochondrial respiratory chain and oxidative phosphorylation. Mechanistically, ferroptosis inhibition corrected the disrupted mitochondrial homeostasis in dedifferentiated SMCs, including enhanced mitochondrial ROS production, dysregulated mitochondrial dynamics, and mitochondrial hyperpolarization, and ultimately inhibited SMC phenotypic switch and growth. Copper-diacetyl-bisN4-methylthiosemicarbazone (CuATSM), an agent used for clinical molecular imaging and that potently inhibits ferroptosis, prevented SMC phenotypic switch, neointimal formation and arterial inflammation in mice. These results indicate that pro-ferroptosis stress is likely to promote SMC phenotypic switch during neointimal formation and imply that inhibition of ferroptotic stress may be a promising translational approach to treat CVDs with SMC phenotype switch.

Peritoneal carcinomatosis secondary to metastatic lung cancer complicated with acute suppurative appendicitis: A case report and literature review.

RATIONALE: Lung cancer (LC) is a malignant tumor with the highest morbidity and mortality in the world. The most common metastatic sites of LC are the brain (47%), bone (36%), liver (22%), adrenal glands (15%), thoracic cavity (11%) and distant lymph nodes (10%). Peritoneal carcinomatosis (PC) is a rare clinical event in LC patients. Considering the rarity and nonspecific clinical symptoms of peritoneal metastasis among LC patients, a case of peritoneal metastasis secondary to LC incidentally observed by laparoscopic appendectomy is unusual. PATIENT CONCERNS: Here, we present a 53-year-old never-smoker woman who presented to the emergency department with a 2-day history of pain in the right abdominal quadrant. Later, laparoscopy revealed acute suppurative appendicitis accompanied by a peritoneal metastatic mass. DIAGNOSIS: The patient was diagnosed with PC secondary to metastatic LC complicated with acute suppurative appendicitis by immunohistochemistry. Positron emission tomography computed tomography (PET CT) findings further strengthen the evidence of PC from LC. OUTCOMES: Based on the results of genomic analysis, the patient received targeted therapy with osimertinib 80 mg/d. LESSONS: Due to the discovery of new targets, the use of molecular therapies improved progression-free survival (PFS) and overall survival (OS), which increases the chance of identifying peritoneal metastasis of LC. For LC patients with abdominal symptoms, clinicians should be aware of the possibility of peritoneal metastasis from LC, especially for patients diagnosed with lung adenocarcinoma or with pleural effusion.

Lead Exposure in Developmental Ages Promotes Aß Accumulation by Disturbing Aß Transportation in Blood-Cerebrospinal Fluid Barrier/Blood-Brain Barriers and Impairing Aß Clearance in the Liver.

Environmental lead exposure is closely related to the progression of Alzheimer's disease (AD). Our previous study has shown that exposure to lead could result in the cholesterol unbalance and increase amyloid-beta (Aß) generation in the brain. However, the potential effect of lead exposure on Aß transportation is poorly reported. In this study, we sought to explore whether lead exposure in developmental ages impaired the integrity of BCSFB and BBB, two highly vascularized structures in the brain in a rat model. The Aß clearance in the liver was also assessed. Our results showed that lead treatment in developmental ages increased the number of TUNEL-positive apoptotic cells in rat choroid plexus and microvessels. Moreover, lead exposure markedly increased pro-inflammatory factors expression including TNF-α and IL-1ß in rat choroid plexus and microvessels. Interestingly, lead treatment increased the expression of AQP-1 and reduced the expression of TTR, two key proteins associated with the functions of choroid plexus and microvessels. Additionally, the expressions of ABCB1, LRP-1, and RAGE, three major receptors responsible for Aß transportation, were disturbed by developmental lead exposure. All these pathologies resulted in Aß1-40 deposition within BCSFB and BBB and malfunctions of these two vascularized structures. Finally, we found that lead treatment remarkably inhibited the gene expression of LRP-1, which is responsible for Aß endocytosis, in the liver tissue of the rat model. Collectively, our results provide the first evidence that developmental lead exposure induces Aß deposition in BCSFB and BBB and impairs Aß clearance in the liver, which would ultimately disturb Aß transportation via choroid plexus/brain microvessels and facilitate Aß deposition in the brain.

Effects of tobacco smoking on cardiovascular disease in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

Background: Patients with systemic lupus erythematosus (SLE) are at increased risk of cardiovascular disease (CVD) compared to the general population. However, little is known about the effects of tobacco smoking on CVD in patients with SLE. Objective: To systematically review and summarize the available literature regarding the effects of tobacco smoking on developing CVD in patients with SLE. Methods: We retrieved relevant studies from the following databases: PubMed, EMBASE, Web of Science and China National Knowledge Internet (CNKI) database. Two reviewers independently reviewed the eligible studies, assessed their validity, and extracted relevant data. Sensitivity and subgroup analyses were performed to distinguish sources of heterogeneity. Results: A total of 10 studies, which comprised 6984 participants, were included in the analysis. The overall quality of evidence was rated as moderate to low. The smoking prevalence among CVD patients was 39.28% (271/690), which was higher than 31.36% (1974/6294) among non-CVD patients. Compared with never-smokers, the risk of developing CVD in current smokers was 1.42 (95% CI: 1.21-1.66). No significant publication bias was found in our meta-analysis. Conclusions: In spite of the several negative results, this study found that current smokers with SLE have an increased risk of developing CVD, although most of the included studies were in low-to-moderate quality. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022338109.

The Effect of Cardiovascular Medications on Disease-Related Outcomes in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.

Background: Multiple studies have revealed that idiopathic pulmonary fibrosis (IPF) patients are more at risk for cardiovascular diseases and that many IPF patients receive cardiovascular medications like statins, angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), and anticoagulants. Existing studies have reported divergent findings on the link between cardiovascular medications and fibrotic disease processes. The aim of this study is to synthesize the evidence on the efficacy of cardiovascular medications in IPF. Methods: We searched studies reporting the effect of cardiovascular medications on IPF in the PubMed, Embase, Web of Science, Cochrane Library, and two Chinese databases (China National Knowledge Infrastructure database and China Wanfang database). We calculated survival data, forced vital capacity (FVC) decline, and IPF-related mortality to assess the efficacy of cardiovascular medications in IPF. We also estimated statistical heterogeneity by using I2 and Cochran Q tests, and publication bias was evaluated by risk of bias tools ROBINS-I. Results: A total of 12 studies were included in the analysis. The included studies had moderate-to-serious risk of bias. Statin use was associated with a reduction in mortality (hazard ratio (HR), 0.89; 95% CI 0.83-0.97). Meta-analysis did not demonstrate any significant relationship between statin use and the FVC decline (HR, 0.86; 95% CI 0.73-1.02), ACEI/ARB use, and survival data (HR, 0.92; 95% CI 0.73-1.15) as well as anticoagulant use and survival data (HR, 1.16; 95% CI 0.62-2.19). Conclusion: Our study suggested that there is a consistent relationship between statin therapy and survival data in IPF population. However, there is currently insufficient evidence to conclude the effect of ACEI, ARB, and anticoagulant therapy on IPF population especially to the disease-related outcomes in IPF.

Combination of Xuesaitong and Aspirin Based on the Antiplatelet Effect and Gastrointestinal Injury: Study Protocol for a Randomized Controlled Noninferiority Trial.

BACKGROUND: Aspirin is the first-line medication for prevention and treatment of coronary heart disease (CHD). However, long-term use of aspirin resulting in gastrointestinal mucosal injury and bleeding limits the regularity of medication. Xuesaitong is a marketed Chinese medicine contained main active component in Panax notoginseng saponins (PNS), which can significantly inhibit platelet aggregation in patients with CHD. Our previous studies have already showed that PNS could reduce the gastrointestinal mucosal injury caused by aspirin in preclinical study. However, there is a need for further clinical studies to evaluate synergy and attenuation effect of the combination. METHODS: This trial is a prospectively planned, open-labeled, parallel-grouped, single-centered clinical trial. A total of eligible 480 participants will be randomly allocated into three groups: aspirin group, Xuesaitong group, and drug combination group at a ratio of 1 : 1 : 1. The primary outcome is the change of platelet aggregation rate and calprotectin activity. Secondary outcomes include PAC-1, P-selectin, P2Y12, I-FABP activity, and fecal occult blood. Discussion. The results of the study are expected to provide evidence of high methodological and reporting quality on the synergy function of Xuesaitong and aspirin upon the antiplatelet and anti-gastrointestinal injury effect for CHD. It also provides an experimental basis for clinical rational drug combination therapy. Trial Registration. This trial was registered in the Chinese Clinical Trail Registry, ChiCTR2000036311, on 22 August 2020, http://www.chictr.org.cn/edit.aspx?pid=58798&htm=4.

Inhibition of Aspirin-Induced Gastrointestinal Injury: Systematic Review and Network Meta-Analysis.

Background: Administration of aspirin has the potential for significant side effects of gastrointestinal (GI) injury mainly caused by gastric acid stimulation, especially in long-term users or users with original gastrointestinal diseases. The debate on the optimal treatment of aspirin-induced gastrointestinal injury is ongoing. We aimed to compare and rank the different treatments for aspirin-induced gastrointestinal injury based on current evidence. Methods: We searched PubMed, EMBASE, Cochrane Library (Cochrane Central Register of Controlled Trials), and Chinese databases for published randomized controlled trials (RCTs) of different treatments for aspirin-induced gastrointestinal injury from inception to 1 May 2021. All of the direct and indirect evidence included was rated by network meta-analysis under a Bayesian framework. Results: A total of 10 RCTs, which comprised 503 participants, were included in the analysis. The overall quality of evidence was rated as moderate to high. Eleven different treatments, including omeprazole, lansoprazole, rabeprazole, famotidine, geranylgeranylacetone, misoprostol, ranitidine bismuth citrate, chili, phosphatidylcholine complex, omeprazole plus rebamipide, and placebo, were evaluated in terms of preventing gastrointestinal injury. It was suggested that omeprazole plus rebamipide outperformed other treatments, whereas geranylgeranylacetone and placebo were among the least treatments. Conclusion: This is the first systematic review and network meta-analysis of different treatments for aspirin-induced gastrointestinal injury. Our study suggested that omeprazole plus rebamipide might be considered the best option to treat aspirin-induced gastrointestinal injury. More multicenter, high quality, large sample size randomized controlled trials will confirm the advantages of these medicines in the treatment of aspirin-induced gastrointestinal injury in the future.

Current assessment and management of spontaneous pneumomediastinum: experience in 24 adult patients.

OBJECTIVES: Spontaneous pneumomediastinum (SPM) is an uncommon, benign, self-limited disorder that usually occurs in young adults without any apparent precipitating factor or disease. The purpose of this study was to review our experience in dealing with this entity and detail a reasonable course of assessment and management. METHODS: A retrospective case series was conducted to identify adult patients with SPM who were diagnosed and treated in a single institution between 1993 and 2000. RESULTS: Twenty-four patients were identified who included 18 men and 6 women with a mean age of 17.5 years. Acute onset chest pain was the predominant symptom at presentation. Only half of the patients developed clinically evident subcutaneous emphysema. The most frequent precipitating factor was a history of illegal drug abuse seen in 25% of patients. Other factors included asthmatic bronchospasm, physical activity and violent coughing or vomiting. Chest radiography and computerized tomography (CT) were diagnostic in all cases with CT scan revealing six cases with associated pulmonary abnormalities. Esophagogram and flexible bronchoscopy were selectively used. Twelve patients (50%) were admitted to the hospital. Their mean hospital stay was 2 days. All patients were conservatively treated. In a follow-up of 3-10 years no complications or recurrences were observed. CONCLUSIONS: SPM follows alveolar rupture in the pulmonary interstitium. It shows a rising incidence in young drug users. It has a wide range of clinical features necessitating a high index of suspicion. Chest X-ray and CT scan should be always performed. Hospitalization and aggressive approach should be limited. SPM responds well to conservative treatment and follows a benign natural course.

Lobaplatin combined floxuridine/pirarubicin-based transcatheter hepatic arterial chemoembolization for unresectable primary hepatocellular carcinoma.

PURPOSE: To assess the effect and safety of lobaplatin combinated floxuridine /pirarubicin in transcatheter hepatic arterial chemoembolization(TACE) of unresectable primary liver cancer. PATIENTS AND METHODS: TACE combined with the chemotherapy regimen was used to treat 34 unresectable primary liver cancer patients. DSA/ MRI/CT/blood routine examinations were used to evaluate short term activity and toxicity after 4-5 weeks, the process being repeated if necessary. RESULTS: Among the 34 cases, 1 (2.9%) showed a complete response, 21 (61.7%) a partial response, 8 (23.5%) stable disease, and 4 progressive disease, with a total effective rate of 67.6%. The content of alpha fetoprotein dropped by over 50% in 20 cases (58.8%). The rate of recovery was hepatalgia (88.2%), ascites (47.1%), appetite (55.9%), Performance Status(30.4%). The median follow-up time (MFT) was 281 days (63-558 days), and median progression-free survival was 118.5 days (95%, CI:88.8-148.2 days). Adverse reactions (III-IV grade) were not common, with only 4 cases of vomiting and 2 cases of thrombocytopenia (III grade). CONCLUSIONS: Lobaplatin-based TACE is an effective and safe treatment for primary liver cancer.