Efficacy and safety of pharmacotherapy for refractory or unexplained chronic cough: a systematic review and network meta-analysis

Background: Refractory chronic cough (RCC) has a significant impact on patient's health-related quality of life and represents a challenge in clinical management. However, the optimal treatment for RCC remains controversial. This study aimed to investigate and compare the efficacy and safety of the current pharmacological therapeutic options for RCC. Methods: A systematic review was performed by searching PubMed, Web of Science, Embase, and Ovid databases from January 1, 2008 to March 1, 2023. All randomised control trials (RCTs) reporting outcomes of efficacy or/and safety were included in the Bayesian network meta-analysis. Here, we compared the effects on Leicester Cough Questionnaire (LCQ), Visual Analogue Scale (VAS), and objective cough frequency of patients with RCC. Besides, we also compared the incidence of adverse events (AEs) for analysis of safety. PROSPERO registration: CRD42022345940. Findings: 19 eligible RCTs included 3326 patients and 7 medication categories: P2X3 antagonist, GABA modulator, Transient Receptor Potential (TRP) modulator, NK-1 agonist, opioid analgesic, macrolide, and sodium cromoglicate. Compared with placebo, mean difference (MD) of LCQ and 24 h cough frequency for P2X3 antagonist relief were 1.637 (95% CI: 0.887–2.387) and −11.042 (P = 0.035). Compared with placebo, effect sizes (MD for LCQ and cough severity VAS) for GABA modulator were 1.347 (P = 0.003) and −7.843 (P = 0.003). In the network meta-analysis, gefapixant is the most effective treatment for patients with RCC (The Surface Under the Cumulative Ranking Curves (SUCRA) is 0.711 in LCQ, 0.983 in 24 h cough frequency, and 0.786 in cough severity VAS). Lesogaberan had better efficacy than placebo (SUCRA: 0.632 vs. 0.472) in 24 h cough frequency. Eliapixant and lesogaberan had better efficacy than placebo in cough severity VAS. However, TRP modulator had worse efficacy than placebo. In the meta-analysis of AEs, the present study found P2X3 antagonist had a significant correlation to AEs (RR: 1.129, 95% CI: 1.012–1.259), especially taste-related AEs (RR: 6.216, P < 0.05). Interpretation: In this network meta-analysis, P2X3 antagonist showing advantages in terms of efficacy is currently the most promising medication for treatment of RCC. GABA modulator also showed potential efficacy for RCC but with AEs of the central system. Nevertheless, the role of TRP modulator needed to be revisited. Further research is needed to determine the potential beneficiary population for optimizing the pharmacological management of chronic cough. Funding: National Natural Science Foundation of China ( 81870079), Guangdong Science and Technology Project ( 2021A050520012), Incubation Program of National Science Foundation for Distinguished Young Scholars ( GMU2020-207)

Plexin B2 and Semaphorin 4C Guide T Cell Recruitment and Function in the Germinal Center

Follicular T helper (TFH) cells orchestrate the germinal center (GC) response locally. TFH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here. we define an antigen-independent, contact-dependent, adhesive guidance system for TFH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule, which is highly expressed by GC B cells, and its transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on TFH cells. Sema4C on TFH cells serves as a receptor to sense the GC-presented PlxnB2 cue and biases TFH migration inwards at the GC edge to promote GC access. The absence of PlxnB2 from the GC or Sema4C from TFH cells causes TFH accumulation along the GC border, impairs T-B cell interactions in the GC, and is associated with defective plasma cell production and affinity maturation. Therefore, Sema4C and PlxnB2 regulate GC TFH recruitment and function and optimize antibody responses.This work was funded partly by the Ministry of Science and Technology 973 program (grant 2014CB542501 to H.Q.), the National Natural Science Foundation of China (grants 81425011 and 81330070 to H.Q. and grant 31200670 to L.W.), the Ministry of Science and Technology 863 program (grant 2012AA022403 to L.W.), a China Postdoctoral Science Foundation grant (2013M540970 to L.W.), and the Tsinghua-Peking Center for Life Sciences. H.Q. was supported partly by a Bayer Endowed Chair Professorship

Multiple sex partner behavior in female undergraduate students in China: A multi-campus survey

<p>Abstract</p> <p>Background</p> <p>China is realizing increases in women engaged in premarital sex and multiple sex partner behavior. Our aim was to examine prevalence and determinants of multiple sex partner behavior among female undergraduates in China.</p> <p>Methods</p> <p>Anonymously completed questionnaires were received from 4,769 unmarried female undergraduates, recruited using randomized cluster sampling by type of university and students' major and grade. Items captured demographic, family, peer and work influence, and student factors (major, academic performance, and sex-related knowledge and attitudes). To examine risk factors for sexual behaviors, we used multi-level logistic regression, yielding odds ratios (OR) and 95% confidence intervals (95% CI).</p> <p>Results</p> <p>Of 4,769 female students, 863 (18.10%) reported ever having sexual intercourse, and 5.31% reported having multiple sex partners (29.32% of all women having sexual intercourse). Several demographic, family, peer and work influences, and student factors (including major, performance, knowledge, and attitude toward sex) were risk factors for ever having sex. However, risk factors for multiple sex partners only included working in a place of entertainment, having current close friends that were living with boyfriends, poor academic performance, and positive attitudes toward multiple partners. These women also were more likely to practice masturbation, start having sex at a younger age, have sex with married men and/or men not their "boyfriends" at first coitus, and not use condoms consistently.</p> <p>Conclusion</p> <p>A small but important subset of Chinese female undergraduates is engaged in unprotected sex with multiple sex partners. Interventions need to target at risk women, stressing the importance of consistent condom use.</p

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor–related pneumonitis

BackgroundCheckpoint inhibitor–related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined.MethodsWe conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase’s characteristics.ResultsThere were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P&lt;0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005).ConclusionsThe general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised

Influence of Energy State of Montmorillonite Interlayer Cations on Organic Intercalation

It is well known that the intercalation of montmorillonite (Mt) with organic cations is a fast process. During the intercalation, the interaction between the original cations and the structure layer of Mt keeps changing, and the basal spacing of Mt keeps increasing until an organic environment has been built in the interlayer. Many properties of Mt also change during the intercalation, such as hydrophobic or hydrophilic property and thermal stability. In this research, the impact of intercalation on the properties of Mt was studied by investigating the change in basal spacing and energy that coordinates the interlayer cations during the intercalation of Mt with organic cations. The interaction between interlayer cations and the layers in the Mt structure and the change in the system energy were obtained by using molecular dynamics simulation. All the experiment and calculation results provide a theoretical proof in organic intercalation mechanism

Carbon emission reduction and profit distribution mechanism of construction supply chain with fairness concern and cap-and-trade.

Fairness concern behavior is extremely common in social life, and many scholars are beginning to pay attention to this behavior. In this study, we investigate a two-echelon construction supply chain that consists of a general contractor and a subcontractor under cap-and-trade policy. We study the carbon emission reduction decisions and profit distribution mechanism in the construction supply chain with fairness concern and cap-and-trade. We use the Nash bargaining model to describe the fairness concerns of the construction supply chain members and use the co-opetition model to portray the profit distribution. We show that the fairness concern can impose an adverse influence on firms' profits and decrease the magnitude of their carbon emission reductions. The subcontractor's fairness concern causes greater losses to the construction supply chain's profit. We further demonstrate the impact of fairness concern on the optimal decisions of the general contractor and the subcontractor through numerical analysis

Investigation on the Gas Drainage Effectiveness from Coal Seams by Parallel Boreholes

Gas drainage is an important technology to prevent coal and gas outburst, and the drained gas is a kind of clean energy. The gas pressure can characterize gas drainage effectiveness. In this paper, we investigated the effectiveness of gas drainage by gas pressure. Determined by the space shape of the gas flow field, the gas flow state surrounding the drainage boreholes is radial flow. According to the basic equations of radial flow, discrete equations were achieved by the implicit difference scheme, and then we obtained the gas pressure surrounding the drainage boreholes. Results showed that the midpoint between two holes presents the highest gas pressure, and gas pressure declined from the midpoint of two boreholes to both sides. The midpoint gas pressure of the two holes reflects gas drainage effectiveness in a certain degree. Gas pressure declined with segmented characteristics in the first period decline curve in the form of a cubic curve, and the second period decline curve in the form of a straight line. When the drainage pressure reaches a certain value, the decline rate of gas pressure had little relationship with the drainage negative pressure, mainly influenced by the permeability coefficient. To improve the drainage effectiveness, anti-reflection measures are feasible, instead of increasing the drainage negative pressure. Moreover, the conclusion was verified by field data

Job category differences in the prevalence and associated factors of insomnia in steel workers in China

ObjectivesThis study aimed to investigate the prevalence of insomnia and risk factors among different job categories of steel workers in China, in order to improve their quality of occupational life.Material and MethodsA cross-sectional face-to-face survey was conducted which involved 5834 steel workers from a large enterprise located in northern China, including front-line, maintenance and inspection, and other auxiliary workers. The Athens Insomnia Scale and the Job Content Questionnaire were used to assess the status of insomnia and job stress/social support, respectively. Multivariable logistic regression was used to identify factors influencing insomnia.ResultsThe overall prevalence of insomnia was determined at 42.0% (95% confidence interval: 40.7%–43.2%). For front-line, maintenance and inspection, and other auxiliary workers, the prevalence was 42.3%, 39.8%, and 47.9% (p = 0.001), respectively. The participants with high stress and low support, and those who had experienced ≥2 major life events in the past 12 months, compared to those with low stress and high support, and those without major events, displayed an increased risk of insomnia among all 3 job categories (the adjusted odds ratio ranged 1.56–2.38 and 1.30–1.75, respectively). The educational level, shift work, alcohol consumption, and present illness were identified as influencing factors of insomnia for 1 or 2 job categories.ConclusionsThe prevalence of insomnia was the highest in the group of other auxiliary steel workers among the 3 job categories of steel workers under consideration. While the influencing factors of insomnia differed among the groups, job stress and major life events were common risk factors of insomnia among the 3 categories of steel workers