In the context of the new medical reform,the formation mechanism of drug prices is one of the important is-sues of this round of medical reform.Drug prices involve the interests of drug companies,hospitals,patients,and other parties,so it is particularly important to establish a reasonable mechanism for the formation of drug prices to safeguard the interests of all parties.This paper first analyzes the characteristics of drugs and the drug market,and then discusses the actual situation and challenges faced by the formation mechanism of drug prices.On this basis,it proposes basic principles for drug pricing and opti-mization recommendations for the formation mechanism of drug prices in the context of the new medical reform.This can provide a reference for the country to formulate relevant drug price policies and promote the rational development of drug prices.

In the context of the new medical reform,the formation mechanism of drug prices is one of the important is-sues of this round of medical reform.Drug prices involve the interests of drug companies,hospitals,patients,and other parties,so it is particularly important to establish a reasonable mechanism for the formation of drug prices to safeguard the interests of all parties.This paper first analyzes the characteristics of drugs and the drug market,and then discusses the actual situation and challenges faced by the formation mechanism of drug prices.On this basis,it proposes basic principles for drug pricing and opti-mization recommendations for the formation mechanism of drug prices in the context of the new medical reform.This can provide a reference for the country to formulate relevant drug price policies and promote the rational development of drug prices.

Depression is a frequently-seen mental disorder that profoundly affects the survival and quality of life of individuals.Present clinical medicine therapies for depression are not fully efficacious and novel therapeutic agents and targets remain necessary.Bupleuri Radix-Paeoniae Radix(BR-PRA),an essential and crucial compo-nent of traditional antidepressant compound,possesses the beneficial effect of lowering toxicity and amplifying the antidepressant effect when utilized in combination.The underlying mechanisms of these synergistic effects may involve the suppression of inflammation and oxidative stress,the regulation of monoamine neurotransmitters,brain-derived neurotrophic factors,the modulation of the hypothalamus-pituitary-adrenal axis,and the metabolism of various amino acids and energy.This article summarizes the synergistic effects and antidepressant pharmacological effects of BR-PRA herb-pair,thereby providing valuable insights into the potential advantages of this combination and its potential mechanisms of antidepressant action.

Background The serious air pollution of highway toll booths poses a high occupational exposure risk to toll collectors. It is urgent to develop purification methods suitable for airborne particles and microbial pathogens in highway toll booths. Objective To verify the purification effect of low temperature plasma air purifiers on airborne particles and microbes in highway toll booths. Methods Based on controlled-intervention design, we selected three toll booths in an expressway toll station as on-site experimental locations for 6 d (no-intervention period: the low-temperature plasma purifier was turned off in the first three days; intervention period: the purifier was turned on from 9:00 to 17:00 in the following three days). The indoor and outdoor PM_2.5 and PM₁₀ concentrations were continuously monitored during the study. At 9:00, 12:00, and 17:00 of every day during the experiment, indoor and outdoor air samples were collected to analyze the concentration of airborne culturable colonies with a plankton sampler. Airborne particle samples were collected in the outermost exit continuously from 9:00 to 17:00 every day during the experiment using a medium flow particulate sampler, and the species and relative abundance of fungi and bacteria contained in the samples were analyzed by gene sequencing. Independent-sample t test was used to compare the concentration of indoor PM_2.5, PM₁₀, and culturable colonies between the intervention period and the non-intervention period. α diversity analysis, β diversity analysis, and t test were used to compare the diversity and relative abundance of specific species of bacteria and fungi, as well as typical pathogenic bacteria and fungi in the samples between the non-intervention period and the intervention period to reflect the purification effect of low temperature plasma air purifier on airborne PM_2.5, PM₁₀, and microorganisms. Results During the intervention period, the mean indoor concentrations of PM_2.5, PM₁₀, and culturable colonies were lower than those of the no-intervention period (P<0.01 or P<0.001). The ratios of indoor to outdoor concentration (I/O) of PM_2.5 and PM₁₀ during the intervention period were significantly lower than those of the no-intervention period (P<0.001), except the I/O of culturable colonies. Compared with the average concentration at 9:00, the average cleaning rates at 12:00 and 17:00 for PM_2.5 were 49.0% and 46.1%, for PM₁₀ were 49.7% and 45.4%, for airborne culturable colonies were 50.8% and 49.9%, respectively. The β diversity analysis showed that there were significant differences in composition at the level of species of bacteria, and at the levels of genus and species of fungi between the intervention and the no-intervention periods. The relative abundances of 10 species of bacteria such as Lactobacillus and 7 species of fungi such as Torula in the intervention period were significantly lower than those in the non-intervention period, but the relative abundances of fungi such as unclassified_f_cladosporiaceae, trichomerium, and cercospora were higher (P<0.05). For typical pathogenic bacteria, the relative abundances of Lactobacillus and Clostridium_sensu_stricto_1 during the intervention period were 73.5% and 86.9% lower than those in the no-intervention period, and the relative abundance of Talaromyces was 53.5% lower (P<0.05). Conclusion Low temperature plasma air purifier has a good purification effect on indoor PM_2.5, PM₁₀, and culturable colonies in highway toll booths, and likely a limited effect on some fungi.

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

Constraint-based genome-scale metabolic network models (genome-scale metabolic models, GEMs) have been widely used to predict metabolic phenotypes. In addition to stoichiometric constraints, other constraints such as enzyme availability and thermodynamic feasibility may also limit the cellular phenotype solution space. Recently, extended GEM models considering either enzymatic or thermodynamic constraints have been developed to improve model prediction accuracy. This review summarizes the recent progresses on metabolic models with multiple constraints (MCGEMs). We presented the construction methods and various applications of MCGEMs including the simulation of gene knockout, prediction of biologically feasible pathways and identification of bottleneck steps. By integrating multiple constraints in a consistent modeling framework, MCGEMs can predict the metabolic bottlenecks and key controlling and modification targets for pathway optimization more precisely, and thus may provide more reliable design results to guide metabolic engineering of industrially important microorganisms.
Genome ; Metabolic Engineering ; Metabolic Networks and Pathways/genetics* ; Models, Biological ; Thermodynamics

Allografts ; COVID-19 ; China/epidemiology* ; Disease Outbreaks ; Humans ; Kidney Transplantation/adverse effects* ; SARS-CoV-2

Objective:To explore the clinical features, diagnosis and prognosis of renal transplant recipients with COVID-19.Methods:The clinical data were retrospectively analyzed for 2 kidney transplant recipients with COVID-19. Based upon clinical manifestations, blood routine, inflammatory factors, cell immunity, chest computed tomography(CT)and therapeutic efficacies, the diagnosis and treatment of COVID-19 in kidney transplant recipients(Interim Edition V)were compared to that of ordinary COVID-19 patients. Both recipients had an onset of low/moderate fever. There was no initial symptom of cough or fatigue. Blood routine indicated a normal count of leukocytes, a marked lymphocytopenia, elevated C-reactive protein(CRP)and slightly higher procalcitonin(PCT). Cellular immunity was extremely low and chest CT showed multiple patchy ground-glass opacities in both lungs.Results:After 1 week of onset, both patients had a marked disease progression. The pathogenesis and imaging changes were highly similar to those reported for ordinary COVID-19 patients. For preventing secondary infections, both received symptomatic supportive measures of antiviral agents, withdrawing immunosuppressants, tapering of hormone maintenance dose, intravenous drip of gamma globulin and respiratory supports. Currently the conditions of both patients obviously improved and renal function was stable. One case recovered and was discharged.Conclusions:The clinical manifestations of COVID-19 in renal transplant recipients are generally consistent with that of ordinary COVID-19 patients. Although there is no established treatment for COVID-19, withdrawing immunosuppressants, maintaining small and medium doses of hormones, actively restoring immunity and providing respiratory supports in a timely manner are effective.

Objective: To explore the clinical features, diagnosis and prognosis of renal transplant recipients with NCP. Method: The clinical data of 2 cases of kidney transplant recipients with NCP were retrospectively analyzed. Based onclinical manifestations, blood routine, inflammatory factors, cell immunity, chest CT andtherapeutic effects, the diagnosis and treatment of NCP in kidney transplant recipients (5th edition) were compared to that ofordinary NCP patients. Both recipients developed onset of low andmoderate fever, with no cough or fatigue at the initial stage. Blood routine indicated a normal range of leukocytes,buta significant decrease in lymphocyte counts, increased C-reactive protein (CRP) , and slightly higher procalcitonin (PCT) . The cellular immunity was extremely low, and the chest CT showed multiple patchy ground glass shadows in both lungs. Result: After 1 week of onset, both patients had significant disease progression. The pathogenesis and imaging changes were highly similar tothatreported in ordinary NCP patients.Two patients were givensymptomatic supportive treatment by antiviral agents, stop uses ofimmunosuppression agents, small amount of hormone maintenance, intravenous drip of gamma globulin andrespiratory support toavoid secondary infections. At present, the condition of both patients is obviously improved, and renal function is stable. One of them has recovered and was discharged. Conclusion The clinical manifestations of NCP in renal transplant recipients were generally consistent with that of ordinary NCP patients. Although there is no established method for the treatment of NCP, it is effective by stopping uses of immunosuppressive agents, maintaining small and medium doses of hormones, actively restoring immunity, and providing respiratory support in a timely manner.

Objective To investigate the influence of extracellular high mobility group box 1 (HMGB1) on viral replication in HTLV-1 infected T cells.Methods HMGB1 in culture supernatants of adult T-cell leukemia virus 1 (HTLV-1) virus-negative cell:Jurkat,MOLT4 cells and HTLV-1 virus-positive cells:MT2,MT4,was detected by ELISA;The HTLV-1 long terminal repeat reporter gene (pHTLV-1-LTR-luc) was transfected into MT2 cells by Tfx-50-mediated transfection,and 0.25,0.50,0.75 μg/ml of HMGB1 polyclonal antibody(HMGB1 PcAb) and its isotype control rabbit IgG antibodies,0.03,0.1,0.3 μg/ml rhHMGB1 and its control PBS,were added into culture supernatant respectively,then luciferase activity was detected after 48 h;Similarly,0.25 μg/ml HMGB1 PcAb and the isotype control antibody,0.3 μg/ml rhH-MGB1 and the control PBS were added to the culture supernatant of MT2 cell,the viral gene,pol1,pol2,gag,env,etc,were performed by real-time PCR.Results Culture supernatant HMGB1 levels has no significant difference between HTLV-1 positive cells MT2 and MT4 and the other two virus-negative T cell lines;Compared with isotype control antibody group,the culture supernatant,to which is added 0.25 μg/ml HMGB1 PcAb,can significantly inhibit the HTLV-1-LTR transcriptional activity and suppress the expressions of the viral gene pol1,pol2,gag,env.Compared with the control PBS,0.3 μg/ml rhHMGB1 significantly promotes the transcriptional activity of the HTLV-1-LTR and the expressions of the viral gene pol1,pol2,gag,env.Conclusion The extracellular HMGB1 can promote viral replication of HTLV-1 infected T cells.