Cost-Effectiveness Analysis of Combined Chemotherapy Regimen Containing Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis in China

Objective This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline(BR)and the conventional treatment regimen(CR,not containing Bedaquiline)for the treatment of adults with multidrug-resistant tuberculosis(MDR-TB)in China.Methods A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years.The model parameter data were synthesized from the literature,the national TB surveillance information system,and consultation with experts.The incremental cost-effectiveness ratio(ICER)of BR vs.CR was determined.Results BR(vs.CR)had a higher sputum culture conversion rate and cure rate and prevented many premature deaths(decreased by 12.8%),thereby obtaining more quality-adjusted life years(QALYs)(increased by 2.31 years).The per capita cost in BR was as high as 138,000 yuan,roughly double that of CR.The ICER for BR was 33,700 yuan/QALY,which was lower than China's 1×per capita Gross Domestic Product(GDP)in 2020(72,400 yuan).Conclusion BR is shown to be cost effective.When the unit price of Bedaquiline reaches or falls below57.21 yuan per unit,BR is expected to be the dominant strategy in China over CR.

Acknowledging the Diversity of Modernisation as Foundation of a Common Understanding of Human Rights

Human thinking is apparently caught in dichotomies:it is about the we and the other,the latter often seen as barbarians;it is about the now and then;and all this thinking is characterised by a tension:while the grass seems to be greener on the other side,we are often inclined to refer to our own time,space and organisation as superior.This implies not only the rejection of the notion of equality,but also that there is no equality so between different patterns;it also proves difficult to truly accept diversity,or in other words:to accept that something is different,at least initially,without any valuation.

Novel Strategies for Redirecting NK Cells in Cancer Immunotherapy

Natural killer(NK)cells act as a first line of defense in innate immune system against new malignant transformed cells without prior exposure to tumor antigens.The activity of NK cells is tightly controlled by a balance between inhibitory receptors and activating receptors,and when activation signals outweigh inhibitory signals,NK cells can mediate a response to eliminate the targeted cells.As a bridge between the innate and adaptive immune responses to enhance destruction of tumors,NK cells kill their tumor targets through a variety of mechanisms,including receptor-mediated cytotoxicity,antibody-dependent cell-mediated cytotoxicity(ADCC),death receptor Fas/FasL signaling pathway-mediated cancer apoptosis.However,the efficacy of using NK cells for tumor immunotherapy has been limited by a lack of antigen specificity.To overcome this limitation,Vallera and colleagues developed a bispecific killer cell engager(BiKE),which is comprised of a first ScFv that recognizes a tumor antigen and a second ScFv against CD16(expressed on NK cells)to trigger ADCC.To overcome the poor expansion of NK cells in vivo,a novel trispecific killer cell engager(TriKE)was evolved from the BiKE by the same team.In this molecule,IL-15 was integrated to promote NK cell expansion,thereby eliciting superior NK cytotoxicity and NK cell persistence in vivo compared to BiKE.In order to simultaneously target drug-refractory cancer stem cells(CSC)and cancer cells,a novel tetraspecific killer engager(TetraKE)comprising anti-CD133,EpCAM,CD16 ScFvs and a sustaining IL-15 signal cross-linker was recently developed.Compared to BiKE or TriKE,TetraKE1615EpCAM133 was highly specific against EpCAM-and CD133-bearing cells,leading to enhanced NK cell proliferation,prolonged survival and a limited cytokine response.This TetraKE represents a promising new modality for immunotherapy.

Diagnosis and treatment of post-cholecystectomy diarrhoea

The incidence of cholecystitis is relatively high in developed countries and may usually be attributed to gallstones,the treatment for which involves complete surgical removal of the gallbladder(cholecystectomy).Bile acids produced following cholecystectomy continue to flow into the duodenum but are poorly absorbed by the colon.Excessive bile acids in the colon stimulate mucosal secretion of water and electrolytes leading,in severe cases,to diarrhoea.Bile acid diarrhoea(BAD)is difficult to diagnose,requiring a comprehensive medical history and physical examination in combination with laboratory evaluation.The current work reviews the diagnosis and treatment of BAD following chole-cystectomy.

Role of unc5b in retinal neovascularization in mice with oxygen-induced retinopathy

AIM: To explore the role of unc5b in retinal neovascularization in murine oxygen-induced retinopathy (OIR). METHODS: On postnatal 7 (P7), C57BL/6J mice were exposed to 75% +/- 2% oxygen for 5 days. On postnatal 12 (P12), the mice were brought back to the room air (21% oxygen) to induce retinal neovascularization. Western blot analysis was performed to examine the temporal expression of unc5b in murine retinas. Double staining for unc5b and isolectin B4 were employed to determine the location of unc5b in murine retinas. The effect of unc5b on retinal neovascularization was evaluated by intravitreal injection of unc5b-FC in mice with OIR. Retinal neovascularization was measured by counting neovascular cell nuclei above the internal limiting membrane and by angiography of flat-mounted retinas perfused with fluorescein dextran. o RESULTS: Compared to age-matched normal mice, the expression of unc5b was significantly increased in retinas of OIR mice on P17 and P21. Unc5b was apparently expressed in retinal vessels of OIR while being negative in normal retinal vessels. Retinal neovascularization in eyes injected with unc5b-FC was significantly reduced. CONCLUSION: Unc5b-FC can effectively inhibit retinal neovascularization induced by OIR. It may serve as a powerful and novel therapy for ischemia-induced retinal disease.

Efficacy and safety of acarbose in the treatment of elderly patients with postprandial hypotension

Background Postprandial hypotension （PPH） occurs frequently in elderly people and may lead to syncope, falls, dizziness, weakness, angina pectoris, and stroke. Some studies suggest that the magnitude of the postprandial fall in blood pressure （BP） is influenced by the rate at which glucose enters the small intestine. We hypothesized that acarbose （α-glucosidase inhibitor）, a hypoglycemic agent that decreases the rate of glucose absorption in the small intestine, would attenuate PPH in the elderly, and would be safe in the treatment. Methods Forty-three elderly in-patients with PPH were recruited. All of them were in relatively stable conditions. They had semi-liquid standard meals without and with acarbose for the two following days： screening day and intervention day. Blood pressure and heart rate （HR） were recorded at baseline and every 15 minutes for 120 minutes using a non-invasive ambulatory blood pressure monitoring system during the study, and ejection fraction （EF） and fractional shortening （FS） were measured by two dimensional echocardiography. Results Compared with the screening day, the falls in systolic, diastolic and mean arterial blood pressure （SBP, DBP, MAP） （all P 〈0.05） were significantly attenuated after taking acarbose during breakfast, so were MAP （P 〈0.05） during lunch, DBP （P 〈0.05） and MAP （P 〈0.05） during supper. The change of HR was not statistically significant after taking acarbose in three meals. EF and FS were positively correlated with the relief rate. The effective power was 63%, and the incidence of adverse drug reaction （ADR） was 9%. Conclusion Acarbose is effective and safe in the treatment of elderly patients with PPH.

Chinese-Style Human Rights Reflect Chinese Wisdom

The modernization path the West has taken is very different from that of China,largely because Western-style modernization centers on capital,whereas Chinese-style modernization emphasizes the collective promotion and equitable sharing of development achievements among all Chinese citizens,with the aim of improving the quality of life for all.