Current status of high-risk HPV infection and correlation with multiple infections in cervical lesions in Western Guangzhou.

Objective: This study aims to investigate the current status of multiple HPV infection and its association with cervical lesions in the western region of Guangzhou. Methods: A retrospective analysis of clinical data from cervical cancer screening patients was conducted. The patients were grouped based on HPV genotypes and cervical pathology results to explore the prevalence of high-risk HPV infection and its relationship with cervical lesions in the western region of Guangzhou. The study also analyzed the relationship between high-risk HPV infection and cervical lesions among different age groups. Results: A total of 13,060 patients were included in the study, with an overall infection rate of 18.46% (2,411/13,060). Among them, the infection rate of HPV genotype 16 was 14.14% (341/2,411), HPV genotype 18 was 5.23% (126/2,411), and other 12 high-risk HPV genotypes accounted for 71.96% (1,735/2,411). When comparing the incidence of HSIL+ (high-grade squamous intraepithelial lesion or worse) among different HPV genotypes, the results showed that the HPV 16 infection group (47.50%) had a higher incidence than the HPV 18 infection group (25.40%) and the other 12 high-risk HPV genotypes group (15.97%; P < 0.05). In the multiple infection groups, the pathogenicity rates were 63.64% (7/11) for the 16+18 HPV infection group, 42.97% (55/128) for the 16+other 12 high-risk HPV genotypes infection group, 26.79% (15/56) for the 18+other 12 high-risk HPV genotypes infection group, and 57.14% (8/14) for the 16+18+other 12 high-risk HPV genotypes infection group. These rates were significantly different compared to the single infection group (P <0.01). Although there was no statistically significant difference in the incidence of cervical cancer between the HPV 16 infection group and the HPV 18 infection group, both groups had a higher incidence compared to the group with other 12 high-risk HPV genotypes infection (P < 0.05). Further analysis suggests that the severity of cervical lesions is not associated with the number of high-risk HPV infections, i.e., the severity of cervical lesions is unrelated to multiple HPV infections but is instead related to the pathogenicity of the HPV genotypes. The infection rate and multiple HPV infection rate of women under 35 years old were higher than those of women aged 35 and above (20% vs. 17.1%; 2% vs. 1.3%; P < 0.05). Moreover, the pathogenicity rate of HSIL+ among high-risk HPV infection increased with age. Conclusions: In the western region of Guangzhou, the overall infection rate of high-risk HPV is 18.46%. The severity of cervical lesions is unrelated to multiple HPV infections. The fundamental reason is the distinct pathogenicity of different HPV genotypes. The HSIL+ pathogenicity rates, from high to low, are in sequence for HPV 16, HPV 18, and the other 12 HPV types.

Ferroptotic alveolar epithelial type II cells drive TH2 and TH17 mixed asthma triggered by birch pollen allergen Bet v 1.

Asthma is a common allergic disease characterized by airway hypersensitivity and airway remodeling. Ferroptosis is a regulated death marked by iron accumulation and lipid peroxidation. Several environmental pollutants and allergens have been shown to cause ferroptosis in epithelial cells, but the relationship between birch pollinosis and ferroptosis in asthma is poorly defined. Here, for the first time, we have identified ferroptosis of type II alveolar epithelial cells in mice with Bet v 1-induced asthma. Further analysis revealed that treatment with ferrostatin-1 reduced TH2/TH17-related inflammation and alleviated epithelial damage in mice with Bet v 1-induced asthma. In addition, ACSL4-knocked-down A549 cells are more resistant to Bet v 1-induced ferroptosis. Analysis of clinical samples verified higher serum MDA and 4-HNE concentrations compared to healthy individuals. We demonstrate that birch pollen allergen Bet v 1 induces ferroptosis underlaid TH2 and TH17 hybrid asthma. Lipid peroxidation levels can be considered as a biomarker of asthma severity, and treatment with a specific ferroptosis inhibitor could be a novel therapeutic strategy.

Efficacy and safety of intratonsillar immunotherapy for allergic rhinitis: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: A lower adherence rate existed in patients receiving allergen-specific immunotherapy due to its lengthy period and adverse effects even though it is the only curative treatment for IgE-mediated allergies. Therefore, exploring innovative allergen-specific immunotherapy routes is necessary. OBJECTIVE: To explore the efficacy and safety of the intratonsillar injection of house dust mite (HDM) extract in patients with HDM-induced allergic rhinitis (AR). METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 80 patients with HDM-induced AR were randomized to receive 6 intratonsillar injections with HDM extract or placebo in 3 months. The total nasal symptom score (TNSS), visual analogue scale of nasal symptoms, combined symptom and medication score, mini rhinoconjunctivitis quality of life questionnaire, and serum allergen-specific IgG4 to Dermatophagoides pteronyssinus were all monitored at baseline and 3 months, 6 months, and 12 months after the treatment was finished. The intent-to-treat and per-protocol set (PPS) are both analyzed. RESULTS: The primary end points TNSS and ΔTNSS were improved significantly at 3 months after the patients with AR finished a 3-month 6-injection intratonsillar immunotherapy compared with those in the placebo treatment in both intent-to-treat and PPS. Results of visual analogue scale, combined symptom and medication score, and mini rhinoconjunctivitis quality of life questionnaire were also improved significantly at 3 months after the treatment in PPS. However, the improvement effect of intratonsillar immunotherapy at 6 and 12 months was limited and uncertain based on the data. The increase of serum Der p IgG4 in the active group was significantly higher than that in the placebo group at 3, 6, and 12 months after the treatment was finished. Adverse events were monitored, and no systemic adverse reactions were observed. CONCLUSION: The clinical trial revealed that intratonsillar injection with HDM extract was safe and effective in patients with AR. Optimizing the protocol and allergen formulations is expected to increase and maintain the efficacy of this novel approach. TRIAL REGISTRATION: https://www.chictr.org.cn/index.html, identifier: ChiCTR-TRC-13003600.

Formononetin improves the inflammatory response and bone destruction in knee joint lesions by regulating the NF-kB and MAPK signaling pathways.

Formononetin (FMN) is a phytoestrogen that belongs to the isoflavone family. It has antioxidant and anti-inflammatory effects, as well as, many other biological activities. Existing evidence has aroused interest in its ability to protect against osteoarthritis (OA) and promote bone remodeling. To date, research on this topic has not been thorough and many issues remain controversial. Therefore, the purpose of our study was to explore the protective effect of FMN against knee injury and clarify the possible molecular mechanisms. We found that FMN inhibited osteoclast formation induced by receptor activator of NF-κB ligand (RANKL). Inhibition of the phosphorylation and nuclear translocation of p65 in the NF-κB signaling pathway plays a role in this effect. Similarly, during the inflammatory response of primary knee cartilage cells activated by IL-1ß, FMN inhibited the NF-κB signaling pathway and the phosphorylation of the ERK and JNK proteins in the MAPK signaling pathway to suppress the inflammatory response. In addition, in vivo experiments showed that both low- and high-dose FMN had a clear protective effect against knee injury in the DMM (destabilization of the medial meniscus) model, and the therapeutic effect of high-dose FMN was stronger. In conclusion, these studies provide evidence of the protective effect of FMN against knee injury.

Progress in diagnosis and treatment of ovarian metastases in rectal cancer / 中华胃肠外科杂志

Rectal cancer is the most common tumor of digestive tract. For female patients, ovarian metastasis ranks the second place in intraperitoneal organ metastasis. Its symptoms are occult, easily missed and insensitive to systemic treatment, so the prognosis is poor. Surgery is the treatment of choice for patients with rectal ovarian metastases, whether R0 resection is possible or not, and reducing tumor load is associated with better prognosis. With the continuous development of hyperthermic intraperitoneal chemotherapy (HIPEC), tumor reduction can reach the cellular level, which can significantly improve survival. Prophylactic ovariectomy remains a controversial issue in patients at high risk of ovarian metastasis. In this review, we summarize the diagnosis, treatment and prevention strategies of rectal cancer ovarian metastases, hoping to provide some reference for clinical practice.

Long-term Prophylaxis with Androgens in the management of Hereditary Angioedema (HAE) in emerging countries.

Hereditary angioedema (HAE) is a rare autosomal dominant genetic disease characterized by repetitive subcutaneous or submucosal angioedema, activation of the kinin system, and increased vascular permeability. C1-inhibitor (C1-INH) deficiency, the main mechanism of HAE pathogenesis, occurs when abnormal activation of plasma kallikrein, bradykinin, and factor XII, or mutation of genes such as SERPING1 cause quantitative or functional C1-INH defects. Although androgens are not approved for HAE treatment in many countries, they are widely used in China and Brazil to reduce the frequency and severity of HAE attacks. The long-term adverse effects of androgen treatment are concerning for both physicians and patients. Virilization, weight gain, acne, hirsutism, liver damage, headache, myalgia, hematuria, menstrual disorders, diminished libido, arterial hypertension, dyslipidemia, and anxiety/depression are commonly observed during long-term treatment with androgens. These adverse effects can affect the quality of life of HAE patients and often lead to treatment interruption, especially in women and children. In-depth studies of the pathogenesis of HAE have led to the approval of alternative treatment strategies, including plasma-derived C1 inhibitor, recombinant human C1 inhibitor, plasma Kallikrein inhibitor (ecallantide; lanadelumab), and bradykinin B2 receptor antagonist (icatibant), some of which have achieved satisfactory results with mostly non-serious side effects. Therefore, a new standard of medical care may expand possibilities for the management of HAE in emerging countries.

Chinese Guideline on Allergen Immunotherapy for Allergic Rhinitis: The 2022 Update.

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

Influence of calcareous nodules content on scaling effect in shear strength of cohesive soil containing calcareous nodules.

The difference in the shear strength and other characteristics of the cohesive soil containing calcareous nodules (CSCN) between samples with large size and corresponding scaling size, which is called scaling effect, is significantly affected by its calcareous nodule content (CNC) of the gradation composition. However, current researches rarely reveal the influence of the CNC on the scaling effect in shear strength of samples. In this study, how and why the CNC affects the scaling effect in shear strength were explored. Then a method to reduce the scaling effect based on the reason for influence was proposed. Results show that the correlation between the scaling effect in shear strength and the CNC presents a step curve. This is attributed to that it is easier to form a skeleton effect in samples with scaling size for the same CNC. Considering the skeleton effect, a calculation model for the shear strength parameters of CSCN samples with large size is proposed to reduce the scaling effect. This paper demonstrates that the proposed calculation model provides an access to obtain calculated shear strength parameters of CSCN samples with large size by using measured results of samples with corresponding scaling size.

Exploring the Safety, Effectiveness, and Cost-Effectiveness of a Chinese Patent Medicine (Fufang E'jiao Syrup) for Alleviating Cancer-Related Fatigue: A Protocol for a Randomized, Double-Blinded, Placebo-Controlled, Multicenter Trial.

OBJECTIVE: To provide higher level evidence on the benefits of a Chinese patent medicine (CPM) (Fufang E'jiao Syrup, FFEJS) for alleviating cancer-related fatigue (CRF), this article describes a protocol for a randomized controlled trial. METHODS/DESIGN: We designed a double-blind, placebo-controlled stratified permuted block randomization clinical trial on CRF among 3 types of cancer in China. Participants will be equally allocated to FFEJS group or placebo group according to the randomization sequence and the hospitals they were enrolled at. Each patient will receive 20 ml of either the study formula FFEJS or a placebo formula, 3 times a day for 6 weeks. The follow-up period will be another 4 weeks for safety evaluation. The primary outcome is the difference in improvement of fatigue as measured with the Revised Piper Fatigue Scale-Chinese Version (RPFS-CV). Secondary outcomes include change in fatigue (measured by routine blood panel and hormones in peripheral blood) and QoL (measured by Edmonton symptom assessment scale and Functional Assessment of Cancer Therapy). Patient safety will be measured by liver, renal or cardiac damage, and the risk of FFEJS having a tumor promotion and progression effect will be monitored throughout this study. Cost-effectiveness will also be evaluated mainly by incremental cost per each quality-adjusted life year gained. DISCUSSION: This article describes the study design of a CPM for CRF in patients with advanced cancer through exploring the effectiveness, safety, and cost-effectiveness of FFEJS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04147312. Registered on 1 Sep 2019.

China Consensus Document on Allergy Diagnostics.

The prevalence of allergic diseases has increased dramatically in recent years in China, affecting the quality of life in 40% of the population. The identification of allergens is the key to the diagnosis of allergic diseases. Presently, several methods of allergy diagnostics are available in China, but they have not been standardized. Additionally, cross-sensitization and co-sensitization make allergy diagnostics even more complicated. Based on 4 aspects of allergic disease (mechanism, diagnosis procedures, allergen detection in vivo and in vitro as well as the distribution map of the most important airborne allergens in China) and by referring to the consensus of the European Society of Allergy and Clinical Immunology, the World Allergy Organization, and the important literature on allergy diagnostics in China in recent years, we drafted this consensus of allergy diagnostics with Chinese characteristics. It aims to standardize the diagnostic methods of allergens and provides a reference for health care givers. The current document was prepared by a panel of experts from the main stream of professional allergy associations in China.

Safety of semi-depot house dust mite allergen extract in children and adolescents with allergic rhinitis and asthma.

Aim: Multicenter study to investigate the safety of mite extract product Novo-Helisen Depot, Strengths 1 to 3 (NHD3), as subcutaneous immunotherapy (SCIT), in Chinese children and adolescents with allergic rhinitis (AR) and allergic asthma (AA). Patients & methods: We evaluated SCIT-related adverse events (AEs) during NHD3 14-week initial therapy in children (5-11 years) and adolescents (12-17 years) with perennial symptomatic AR and AA. Results: Among 3600 injections in 250 patients, 361/3600 (10.0%) injections caused SCIT-related AEs in 96/250 (38.4%) patients, 321/3600 injections (8.9%) caused local reactions in 89/250 (35.6%) and 40/3600 injections (1.1%) caused systemic reactions in 23/250 (9.2%). Conclusion: Initial SCIT treatment using NHD3 was safe and well tolerated in Chinese children and adolescents with AR and AA.

Modified Liujunzi Decoction () Alleviates Chemotherapy-Induced Anorexia in Advanced Non-Small Cell Lung Cancer: A Propensity Score Matched Case-Control Study.

OBJECTIVE: To evaluate the effect of Chinese herbal medicine formula, modified Liujunzi Decoction (, MLJZT), for anorexia, utilized as adjunct therapy during chemotherapy treatment for patients with advanced non-small cell lung cancer (NSCLC). METHODS: The study adopted a propensity score-matched design based on a prospective database. From February 2016 to September 2017, patients with advanced NSCLC that received both cisplatin-based chemotherapy and MLJZT (IM group) were 1:1 propensity score-matched to patients that received the cisplatin-based chemotherapy alone (control group). Changes in anorexia and weight, as well as side effects were evaluated per week within 4-cycle chemotherapy. RESULTS: Overall, 156 patients with advanced NSCLC that had received chemotherapy from our database were identified and 53 pairs were matched successfully. In total, 48.6% (50/53) of patients in the IM group had anorexia-improvement compared to 28.3% (15/53) of patients in the control group, and a total of 39.6% (21/53) of patients in the control group had a worsening of anorexia compared to only 7.8% (8/53) of patients in the IM group (P<0.01). The weight reduced significantly over time in the control group (-2.36 ± 2.53 kg) as compared to the IM group (-0.62 ± 3.89 kg, P<0.01). CHM didn't reduce the efficacy of chemotherapy in shrinking tumor size, and didn't increase the incidence of side effects such as hematological and hepatorenal toxicity. CONCLUSION: MLJZT is effective and safe for alleviating anorexia in patients with NSCLC. These findings warrant the conduct of a randomized controlled trial.

Chinese Guideline on allergen immunotherapy for allergic rhinitis.

The present document is based on a consensus reached by a panel of experts from Chinese Society of Allergy (CSA) and Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G). Allergen immunotherapy (AIT), has increasingly been used as a treatment for allergic rhinitis (AR) globally, as it has been shown to provide a long-term effect in improving nasal and ocular symptoms, reducing medication need, and improving quality of life. AIT is currently the only curative intervention that can potentially modify the immune system in individuals suffering from AR and prevent the development of new sensitization and the progression of disease from AR to asthma. Although the use of AIT is becoming more acceptable in China, to date no AR immunotherapy guideline from China is available for use by the international community. This document has thus been produced and covers the main aspects of AIT undertaken in China; including selection of patients for AIT, the allergen extracts available on the Chinese market, schedules and doses of allergen employed in different routes of AIT, assessment of effect and safety, patients' administration and follow-up, and management of adverse reactions. The Chinese guideline for AR immunotherapy will thus serve as a reference point by doctors, healthcare professionals and organizations involved in the AIT of AR in China. Moreover, this guideline will serve as a source of information for the international community on AIT treatment strategies employed in China.

A highly emissive and stable zinc(ii) metal-organic framework as a host-guest chemopalette for approaching white-light-emission.

A new adenine-containing metal-organic framework (MOF), [Zn4O(adenine)4(benzene-1,3-dicarboxylate)4Zn2] (named as ZnBDCA), was synthesized solvothermally. ZnBDCA possesses high quantum yield (>50%) and nano-channels that can encapsulate acriflavine molecules to build a host-guest chemopalette for approaching white-light emission.

Semi-depot house-dust mite allergen extract for Chinese with allergic rhinitis and asthma.

BACKGROUND: Real-world data of the subcutaneous immunotherapy (SCIT) with semi-depot house-dust mite (HDM) allergen extract (a HDM allergen extract that contains a 50%-50% mixture of Dermatophagoides pteronyssinus and Dermatophagoides farina) for allergic rhinitis and asthma was unavailable in China until recently. AIM: To investigate the effectiveness and safety of a HDM-SCIT for allergic rhinitis and asthma in Chinese patients. METHODS: A multicenter, single-arm, open-label, self-controlled study. Chinese patients with allergic rhinitis or allergic asthma and with a history of symptoms from HDM exposure were included and received allergen-specific immunotherapy for 1 year by subcutaneous injection of HDM-SCIT. The primary outcome measure was the percentage of patients with an improvement in symptom severity assessed at 12 months after initiation of the treatment. The occurrence of adverse events and compliance of treatment were also evaluated. RESULTS: A total of 272 outpatients were included for effectiveness analysis. The subject-evaluated improvement rate in the visual analog scale (VAS) was 76.1% and 71.3% at 6 and 12 months, respectively; corresponding values for investigator-evaluated VAS were 77.9% and 71.7%, respectively (p < 0.0001). Symptom score changes were -2.43 and -3.79 at 6 and 12 months, respectively (both p < 0.0001); the VAS improvement rate and symptom score change did not differ significantly between children and adolescents and/or adults. Good injection schedule adherence was found in 98.8% of the patients. No study drug-related serious adverse events or serious systemic allergic reactions occurred. CONCLUSION: HDM-SCIT was safe and effective in the treatment of allergic rhinitis and asthma in a Chinese population, with good compliance.

Efficacy of Sublingual Immunotherapy with Dermatophagoides farinae Extract in Monosensitized and Polysensitized Patients with Allergic Rhinitis: Clinical Observation and Analysis.

AIM: To investigate differences in the efficacy of sublingual immunotherapy with Dermatophagoides farinae drops in monosensitized and polysensitized allergic rhinitis patients. METHODS: The patients enrolled in the study were treated for more than one year by sublingual immunotherapy (SLIT) using Dermatophagoides farinae drops and were divided into a monosensitized group (n = 20) and a polysensitized group (n = 30). Total nasal symptom scores of patients before and after SLIT were analyzed to evaluate the curative effect. The phylogenetic tree of dust mite allergens as well as other allergens that were tested by skin prick test was constructed to help the analysis. RESULTS: There was no significant difference in the efficacy of SLIT between dust mite monosensitized and polysensitized patients. CONCLUSIONS: Both dust mite monosensitized and polysensitized patients could be cured by SLIT using Dermatophagoides farinae drops. This study provides a reference for the selection of allergens to be used in immunotherapy for polysensitized AR patients.

Expression and refolding of mite allergen pro-Der f1 from inclusion bodies in Escherichia coli.

House dust mite (Dermatophagoides farinae) allergen Der f1 is one of the most important indoor allergens associated with asthma, eczema and allergic rhinitis in humans. Therefore, sufficient quantities of Der f1 cysteine protease to be used for both experimental and therapeutic purposes are very much needed. Using recombinant DNA technology, high expression rates of cysteine proteases were obtained. The cDNA sequence encoding pro-Der f1 was cloned and expressed in Escherichia coli using the T7 based expression vector pET-44a and induced by isopropyl-ß-d-thiogalactoside at a final concentration of 0.2mM. Recombinant pro-Der f1 (pro-rDer f1) was expressed as an inclusion body and the isolated protease was solubilized, refolded and purified. The protease activities and IgE reactivities of pro-rDer f1 that were refolded by size-exclusion chromatography (SEC) were higher than those obtained by dilution. The pair of pro-rDer f1 polypeptides produced by this method could be used for more effective and safer allergen-specific immunotherapy or to produce enzymatically and immunologically active Der f1 for diagnostic testing and deciphering of immunotherapy mechanisms.

Reduction of the number of major representative allergens: from clinical testing to 3-dimensional structures.

Vast amounts of allergen sequence data have been accumulated, thus complicating the identification of specific allergenic proteins when performing diagnostic allergy tests and immunotherapy. This study aims to rank the importance/potency of the allergens so as to logically reduce the number of allergens and/or allergenic sources. Meta-analysis of 62 allergenic sources used for intradermal testing on 3,335 allergic patients demonstrated that in southern China, mite, sesame, spiny amaranth, Pseudomonas aeruginosa, and house dust account for 88.0% to 100% of the observed positive reactions to the 62 types of allergenic sources tested. The Kolmogorov-Smironov Test results of the website-obtained allergen data and allergen family featured peptides suggested that allergen research in laboratories worldwide has been conducted in parallel on many of the same species. The major allergens were reduced to 21 representative allergens, which were further divided into seven structural classes, each of which contains similar structural components. This study therefore has condensed numerous allergenic sources and major allergens into fewer major representative ones, thus allowing for the use of a smaller number of allergens when conducting comprehensive allergen testing and immunotherapy treatments.