Efficacy and Safety of Dupilumab in Chinese Elderly Patients with Atopic Dermatitis: A Real-World Study.

INTRODUCTION: With the aging of the population in China, the prevalence of atopic dermatitis (AD) is high in elderly patients. These patients usually have more comorbidities and they need more effective and safer treatments. Dupilumab is an anti-interleukin-4 (IL-4) receptor monoclonal antibody which was approved for the treatment of moderate-to-severe AD. METHODS: Elderly patients (60 years or older) with moderate-to-severe AD who treated with dupilumab were included. Eczema Area and Severity Index (EASI) score, Peak Pruritus Numerical Rating Scale (PP-NRS), EASI-50, EASI-75, and EASI-50 were evaluated. The efficacy in subgroups was also investigated. RESULTS: Fifty-eight patients were enrolled. The EASI score and PP-NRS score were significantly reduced at weeks 4, 16, 28, and 52. 91.2% and 79.4% of the patients achieved EASI-50 and EASI-75 at week 16, respectively. 95.8% and 87.5% patients achieved EASI-50 and EASI-75 at week 52, respectively. Adverse events were reported in 10 (17.2%) patients, and no severe adverse event was reported. Male, older age, and moderate AD (EASI <21) were related to better efficacy. CONCLUSIONS: This study demonstrated that dupilumab is effective and safe in elderly patients with AD.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Oxymatrine Alleviates Hyperglycemic Cerebral Ischemia/Reperfusion Injury via Protecting Microvessel.

Hyperglycemia aggravates cerebral ischemia/reperfusion (I/R) injury via vascular injury. There is still a lack of effective pharmaceutical preparations for cerebral I/R injury under hyperglycemia. This study aimed to investigate the effects of oxymatrine (OMT) on hyperglycemia-exacerbated cerebral I/R injury in vitro and in vivo. The middle cerebral artery occlusion (MCAO) and reperfusion was established in the rats under hyperglycemia. Meanwhile, oxygen-glucose deprivation and reoxygenation (OGD/R) with high glucose was used as an in vitro model of hyperglycemic cerebral I/R injury. The results showed that the neurological deficit score, mortality, infarct volume and penumbra apoptosis in hyperglycemia group were significantly higher than those in normal glucose group. OMT pre-treated obviously reduced the degree of neurological deficit, mortality, infarct volume, improve cerebral blood flow after I/R in rats with hyperglycemia, and increase the survival rate of human brain microvascular endothelial cells (HBMECs) in high glucose and OGD/R group. OMT significantly improved the ultrastructure changes of endothelial cells, and maintain the migration and angiogenesis potency of HBMECs in high glucose and OGD/R group. OMT obviously alleviated the down-regulating CD31 and CD105 expression in cerebral microvessels caused by hyperglycemia. It is concluded that OMT treatment might alleviate cerebral I/R injury under hyperglycemia via protecting microvessels.

Design and synthesis of novel macrolones bridged with linkers from 11,12-positions of macrolides.

Resistance to telithromycin and off-target effects associated with the metabolic instability present serious and challenging problems for the development of novel macrolides. Herein, studies of hybrids of macrolides and quinolones (termed macrolones) bridged with linkers from 11,12-cyclic carbamate of macrolides revealed different structure-activity relationships from the previously reported macrolones bridged with linkers derived from 6-, 9- and 4''-positions of macrolides. The optimized macrolone 34 g with a longer and rigid sidechain than telithromycin had improved metabolic stability compared to telithromycin (t1/2: 110 vs 32 min), whose future has been heavily clouded by metabolic issues. Moreover, 34 g was 38-fold more potent than telithromycin against A2058/2059-mutated Mycoplasma pneumoniae (8 vs 315 µM), which may be attributed to a novel mode of action between the carboxylic acid of quinolone moiety and the bacterial ribosome. This work increases the prospect for discovery of novel and safe antibacterial agents to combat serious human infectious diseases.

A multi center real world observation to evaluate the efficacy of cryotherapy versus local hyperthermia for the treatment of plane warts.

Most plane warts are recalcitrant to treatment. Both cryotherapy and local hyperthermia have been applied to treat plane warts. However, no direct comparative study on their respective efficacy and safety has ever been performed. To assess the efficacy and safety of local hyperthermia at 43 ± 1°C versus liquid nitrogen cryotherapy for plane warts. Sequential patients with plane warts entered the study, either receiving cryotherapy or local hyperthermia therapy at the discretion of the patients and the recommendations of consultants. Cryotherapy with liquid nitrogen was delivered in two sessions 2 weeks apart, while local hyperthermia was delivered on three consecutive days, plus two similar treatments 10 ± 3 days later. The temperature over the treated skin surface was set at 43 ± 1°C for 30 min in each session. The primary outcome was the clearance rates of the lesions 6 months after treatment. Among the 194 participants enrolled, 183 were included in the analysis at 6 months. Local hyperthermia and cryotherapy achieved clearance rates of 35.56% (48/135) and 31.25% (15/48), respectively (p = 0.724); recurrence rates of 16.67% (8/48) and 53.33% (8/15) (p = 0.01); and adverse events rates of 20.74% (28/135) and 83.33% (40/48), respectively (p < 0.001). Cryotherapy had a higher pain score (p < 0.001) and a longer healing time (p < 0.001). Local hyperthermia at 43°C and cryotherapy had similar efficacy for plane warts. Local hyperthermia had a safer profile than cryotherapy but it required more treatment visits during a treatment course. More patients preferred local hyperthermia due to its treatment friendly nature.

Local Hyperthermia Versus Cryotherapy for Treatment of Plantar Warts: A Prospective Multi-centre Non-randomized Concurrent Controlled Clinical Trial.

Cryotherapy is one of the most common treatments for warts; however, pain during treatment and relatively high recurrence rates limit its use. Local hyperthermia has also been used successfully in the treatment of plantar warts. The aim of this study was to compare the clinical effectiveness of local hyperthermia vs cryotherapy for the treatment of plantar warts. This multi- centre, open, 2-arm, non-randomized concurrent controlled trial included 1,027 patients, who received either cryotherapy or local hyperthermia treatment. Three months after treatment, local hyperthermia and cryotherapy achieved complete clearance rates of 50.9% and 54.3%, respectively. Recurrence rates were 0.8% and 12%, respectively. Pain scores during local hyperthermia were significantly lower than for cryotherapy. Both local hyperthermia and cryotherapy demonstrated similar efficacy for clearance of plantar warts; while local hyperthermia had a lower recurrence rate and lower pain sensation during treatment.

Uncoupling Protein 2 Deficiency Enhances NLRP3 Inflammasome Activation Following Hyperglycemia-Induced Exacerbation of Cerebral Ischemia and Reperfusion Damage In Vitro and In Vivo.

Mitochondrial uncoupling protein 2 (UCP2) deficiency exacerbates brain damage following cerebral ischemia/reperfusion (I/R). The Nod-like receptor protein-3 (NLRP3) inflammasome also plays a vital role in cerebral I/R damage. However, the effect of UCP2 on NLRP3 inflammasome-mediated hyperglycemia and I/R damage is not clear. In the present study, UCP2-knockout (UCP2-/-) and wild-type (WT) mice were used to establish a model of middle cerebral artery occlusion (MCAO) and reperfusion under normo- and hyperglycemic conditions. HT22 cells were established as a model of oxygen-glucose deprivation and reoxygenation (OGD/R) with high glucose to mimic hyperglycemia and I/R in vitro. HT22 cells were treated with/without different concentrations of the UCP2-specific inhibitor genipin for different periods of time. The results showed that UCP2 deficiency significantly increased histopathological changes and apoptosis after cerebral I/R damage in hyperglycemic mice. Moreover, UCP2 deficiency enhanced NLRP3 inflammasome activation in neurons when cerebral I/R damage was exacerbated by hyperglycemia. Furthermore, UCP2 deficiency enhanced NLRP3 inflammasome activation and reactive oxygen species (ROS) production in HT22 cells under OGD/R and high-glucose conditions. UCP2 deficiency aggravated hyperglycemia-induced exacerbation of cerebral I/R damage. UCP2 deficiency also enhanced NLRP3 inflammasome activation and ROS production in neurons in vitro and in vivo. These findings suggest that UCP2 deficiency enhances NLRP3 inflammasome activation following hyperglycemia-induced exacerbation of cerebral I/R damage in vitro and in vivo. UCP2 may be a potential therapeutic target for hyperglycemia-induced exacerbation of cerebral I/R damage.

The Involvement of Mitochondrial Biogenesis in Selenium Reduced Hyperglycemia-Aggravated Cerebral Ischemia Injury.

Selenium has been shown to possess antioxidant and neuroprotective effects by modulating mitochondrial function and activating mitochondrial biogenesis. Our previous study has also suggested that selenium protected neurons against glutamate toxicity and hyperglycemia-induced damage by regulating mitochondrial fission and fusion. However, it is still not known whether the mitochondrial biogenesis is involved in selenium alleviating hyperglycemia-aggravated cerebral ischemia reperfusion (I/R) injury. The object of this study is to define whether selenium protects neurons against hyperglycemia-aggravated cerebral I/R injury by promoting mitochondrial biogenesis. In vitro oxygen deprivation plus high glucose model decreased cell viability, enhanced reactive oxygen species production, and meanwhile stimulated mitochondrial biogenesis signaling. Pretreated with selenium significantly decreased cell death and further activated the mitochondrial biogenesis signaling. In vivo 30 min of middle cerebral artery occlusion in the rats under hyperglycemic condition enhanced neurological deficits, enlarged infarct volume, exacerbated neuronal damage and oxidative stress compared with normoglycemic ischemic rats after 24 h reperfusion. Consistent to the in vitro results, selenium treatment alleviated ischemic damage in hyperglycemic ischemic animals. Furthermore, selenium reduced the structural changes of mitochondria caused by hyperglycemic ischemia and further promoted the mitochondrial biogenesis signaling. Selenium activates mitochondrial biogenesis signaling, protects mitochondrial structure integrity and ameliorates cerebral I/R injury in hyperglycemic rats.

[Prevalence of erectile dysfunction and the associated factors in infertile males].

OBJECTIVE: To investigate the prevalence of ED and the associated factors in infertile males. METHODS: We continuously selected 896 infertile males present at Peking Union Medical College Hospital, Dongzhimen Hospital and the Sixth Medical Center of PLA General Hospital and evaluated the erectile function of the patients using a self-designed questionnaire and IIEF-5. We analyzed the ED-associated factors by multivariate analysis. RESULTS: Based on the results of questionnaire investigation, there were 416 cases of ED in the 896 infertile males (46.43%), including 23 (2.56%) severe, 38 (4.24%) moderate, 109 (12.17%) mild-moderate and 246 (27.46%) mild cases. Multivariate analysis indicated that the prevalence rate of ED was correlated positively with obesity, hypertension and diabetes, and negatively with husband-wife affection and the frequency of sexual intercourse. CONCLUSIONS: The prevalence rate of ED is high in infertile males, mostly mild, and correlated with husband-wife affection, the frequency of sexual intercourse and some diseases.

Coenzyme Q10 Protects Astrocytes from Ultraviolet B-Induced Damage Through Inhibition of ERK 1/2 Pathway Overexpression.

Overexpression of extracellular signal-regulated kinase ½ (ERK ½) signaling pathway leads to overproduction of reactive oxygen species (ROS) which induces oxidative stress. Coenzyme Q10 (CoQ10) scavenges ROS and protects cells against oxidative stress. The present study was designed to examine whether the protection of Coenzyme Q10 against oxidative damage in astrocytes is through regulating ERK 1/2 pathway. Ultraviolet B (UVB) irradiation was chosen as a tool to induce oxidative stress. Murine astrocytes were treated with 10 µg/ml and 25 µg/ml of CoQ10 for 24 h prior to UVB and maintained during UVB and 24 h post-UVB. Cell viability was evaluated by counting viable cells and MTT conversion assay. ROS production was measured using fluorescent probes. Levels of p-ERK 1/2, ERK 1/2, p-PKA, PKA were detected using immunocytochemistry and/or Western blotting. The results showed that UVB irradiation decreased the number of viable cells. This damaging effect was associated with accumulation of ROS and elevations of p-ERK 1/2 and p-PKA. Treatment with CoQ10 at 25 µg/ml significantly increased the number of viable cells and prevented the UVB-induced increases of ROS, p-ERK 1/2, and p-PKA. It is concluded that suppression of the PKA-ERK 1/2 signaling pathway may be one of the important mechanisms by which CoQ10 protects astrocytes from UVB-induced oxidative damage.

Penile pyoderma gangrenosum: Successful treatment with thalidomide.

Pyoderma gangrenosum (PG) is a rare ulcerating inflammatory neutrophilic dermatosis. Different clinical manifestations have been described, including ulcerative, pustular and bullous, and vegetative variants. Classic PG usually occurs on the lower extremities (~70% of cases) but can also involve the hands, head, neck, and scrotum. Genital involvement of PG has rarely been reported. Treatment of the genital PG is usually difficult and resistance to conventional therapeutic regimens was frequently observed. The present authors reported a 16-year-old male patient who presented with progressive genital ulceration for 3 weeks. He was treated successfully low dose thalidomide (50 mg/d) and minocycline.

Think twice before stent insertion for renal artery aneurysm with elusive etiology: a case report.

BACKGROUND: Endovascular treatment has been recognized as the first line therapy for renal artery aneurysm (RAA). However, RAA related with malignancies had been sporadically reported in the literature. Stent insertion should be contraindicated for RAAs with malignant etiology, whereas surgery be optimal. CASE PRESENTATION: A 40-year-old female underwent covered stent insertion to exclude the left RAA for suspected Takayasu arteritis in a reginal hospital. Three months later the RAA recurred with sign of threatened rupture, and the patient was transferred for salvage embolization with coils and thrombin injection. However, 20 days after the embolization procedure, multiple painful subcutaneous nodules developed in her flanks. Undifferentiated sarcoma was revealed by the pathological biopsy of the nodules. The RAA in this case was most likely related with the malignancy. CONCLUSION: Malignancy was the most likely etiology behind recurrent aneurysm in this case. Definite diagnosis is mandatory for interventional radiologists before stent insertion for treatment of RAA.

miR-448-3p controls intracranial aneurysm by regulating KLF5 expression.

microRNAs (miRNAs) control several processes known to be involved in progression of aneurysm. Here, intracranial aneurysms (IAs) were surgically induced in Sprague-Dawley rats, and we found that miR-448-3p was downregulated and KLF5 was upregulated in IA rats. We identified Klf5 as a direct target of miR-448-3p in smooth muscle cells (SMCs). In addition, aneurysms size and the lumen area of the aneurysms were smaller 4 weeks after IA induction in the miR-448-3p-treated group. miR-448-3p treatment protected the wall thickness ratio and suppressed macrophage infiltration after IA induction. IAs caused a significant increase in KLF5 expression and were alleviated by miR-448-3p. Moreover, the anti-inflammatory effect of miR-448-3p was verified in lipopolysaccharide -stimulated RAW 264.7 macrophage cells. The expression levels of KLF5, MMP2, and MMP9 levels were elevated by LPS, and were attenuated by miR-448-3p. These data suggest that miR-448-3p plays the inhibitory role in IA progression, indicating that miR-448-3p overexpression is crucial for preventing the development of IA through downregulation of macrophage-mediated inflammation.

Rapid Identification and Subtyping of Enterobacter cloacae Clinical Isolates Using Peptide Mass Fingerprinting.

OBJECTIVE: To establish a domestic database of Enterobacteria cloacae (E. cloacae), and improve the identification efficiency using peptide mass fingerprinting. METHODS: Peptide mass fingerprinting was used for the identification and subtyping of E. cloacae. Eighty-seven strains, identified based on hsp60 genotyping, were used to construct and evaluate a new reference database. RESULTS: Compared with the original reference database, the identification efficiency and accuracy of the new reference database was greatly improved at the species level. The first super reference database for E. cloacae identification was also constructed and evaluated. Based on the super reference database and the main spectra projection dendrogram, E. cloacae strains were divided into two clades. CONCLUSION: Peptide mass fingerprinting is a powerful method to identify and subtype E. cloacae, and the use of this method will allow us to obtain more information to understand the heterogeneous organism E. cloacae.

[Progress in the treatment of premature ejaculation].

Premature ejaculation is a common disease in adult males, which may severely affect the mental health and distort the spousal relationship of the males. Treatment of premature ejaculation aims at increasing the intra-vaginal ejaculation latency time, enhancing the control of ejaculation and improving sexual satisfaction, and comprehensive treatment may help most to achieve these objectives. Though drug therapy remains an important option, there are many other effective strategies for the treatment of premature ejaculation, including psychotherapy, behavioral therapy, traditional Chinese medicine treatment, and surgery. Recently, various studies have demonstrated even better effects of a combination of the above strategies on premature ejaculation.

Selenium suppresses glutamate-induced cell death and prevents mitochondrial morphological dynamic alterations in hippocampal HT22 neuronal cells.

BACKGROUND: Previous studies have indicated that selenium supplementation may be beneficial in neuroprotection against glutamate-induced cell damage, in which mitochondrial dysfunction is considered a major pathogenic feature. However, the exact mechanisms by which selenium protects against glutamate-provoked mitochondrial perturbation remain ambiguous. In this study glutamate exposed murine hippocampal neuronal HT22 cell was used as a model to investigate the underlying mechanisms of selenium-dependent protection against mitochondria damage. RESULTS: We find that glutamate-induced cytotoxicity was associated with enhancement of superoxide production, activation of caspase-9 and -3, increases of mitochondrial fission marker and mitochondrial morphological changes. Selenium significantly resolved the glutamate-induced mitochondria structural damage, alleviated oxidative stress, decreased Apaf-1, caspases-9 and -3 contents, and altered the autophagy process as observed by a decline in the ratio of the autophagy markers LC3-I and LC3-II. CONCLUSION: These findings suggest that the protection of selenium against glutamate stimulated cell damage of HT22 cells is associated with amelioration of mitochondrial dynamic imbalance.

Use of a dose-response model to guide future clinical trial of benvitimod cream to treat mild and moderate psoriasis.

OBJECTIVE: To investigate the time-dose-response relationship of benvitimod cream after topical administration in patients with mild and moderate psoriasis vulgaris for dosage regimen exploring. METHODS: 36 patients with mild and moderate psoriasis vulgaris were randomly assigned to receive 0.5%, 1.0%, 1.5%, and 0% (placebo) benvitimod cream of 30 g/1.7 m2 twice daily for 6 weeks. The primary efficacy outcome was the proportion of patients achieving more than 75% change of the psoriasis area and severity index (PASI 75) from baseline. A longitudinal Emax model was established using the NONMEM method, and then applied to try to find an appropriate dose for following trials. RESULTS: In the final time-dose-response model, the primary outcome at week 6 of PASI 75 of the 0.5%, 1.0%, and 1.5% benvitimod cream was 31%, 63%, and 75%, respectively, demonstrating that the 1.0% benvitimod cream was an appropriate dose for the next trial. The time parameters of ET50 and ET90 were 15 and 69 days for 1.0% benvitimod cream, indicating that the maximum efficacy of PASI change rate was obtained at approximately week 10. The accuracy of PASI change rate by extrapolation prediction was limited at week 10, so the treatment period should be longer in future trials. CONCLUSIONS: The established dose-response model could well describe the relationship between PASI change rate and doses of benvitimod cream in patients with mild and moderate psoriasis vulgaris. This modeling approach may help choose 1.0% benvitimod cream twice daily as a dosage regimen in following clinical trials.

The Role of miRNAs in Cartilage Homeostasis.

Osteoarthritis (OA) is an age-related disease with poorly understood pathogenesis. Recent studies have demonstrated that miRNA might play a key role in OA initiation and development. We reviewed recent publications and elucidated the connection between miRNA and OA cartilage anabolic and catabolic signals, including four signaling pathways: TGF-ß/Smads and BMPs signaling, associated with cartilage anabolism; and MAPK and NF-KB signaling, associated with cartilage catabolism. We also explored the relationships with MMP, ADAMTS and NOS (NitricOxide Synthases) families, as well as with the catabolic cytokines IL-1 and TNF-α. The potential role of miRNAs in biological processes such as cartilage degeneration, chondrocyte proliferation, and differentiation is discussed. Collective evidence indicates that miRNAs play a critical role in cartilage degeneration. These findings will aid in understanding the molecular network that governs articular cartilage homeostasis and in to elucidate the role of miRNA in the pathogenesis of OA.