UNASSIGNED: Implantable cardioverter defibrillator (ICDs) for primary prevention (PP) of sudden cardiac arrest (SCA) is underutilized in developing countries. The Improve SCA study has identified a subset of 1.5 primary prevention (1.5PP) patients with a higher risk of SCA and a significant mortality benefit from ICD therapy. From the perspective of China\'s healthcare system, we evaluated the cost-effectiveness of ICD therapy vs. no ICD therapy among 1.5PP patients with a view to informing clinical and policy decisions.
UNASSIGNED: A published Markov model was adjusted and verified to simulate the course of the disease and describe different health states of 1.5PP patients. The patient characteristics, mortality, utility and complication estimates were obtained from the Improve SCA study and other literature. Cost inputs were sourced from government tender prices, medical service prices and clinical experts\' surveys in 9 Chinese public hospitals. For both ICD and no ICD therapy, the total medical costs and quality-adjusted life-years (QALYs) were modelled over a lifetime horizon and the incremental cost-effectiveness ratio (ICER) was calculated. Deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of the model parameters. We used the willingness-to-pay (WTP) threshold recommended by China Guidelines for Pharmacoeconomic Evaluations, one to three times China\'s GDP per capita (CNY85,698-CNY257,094) in 2022 Chinese Yuan.
UNASSIGNED: The incremental cost effectiveness ratio (ICER) of ICD therapy compared to no ICD therapy is 139,652 CNY/QALY, which is about 1-2 times China\'s GDP per capita. The probability that ICD therapy is cost effective was 92.1%. Results from sensitivity analysis supported the findings of the base case.
UNASSIGNED: ICD therapy compared to no ICD therapy is cost-effective for the 1.5PP patients in China.

UNASSIGNED: For hospitalized patients with chronic obstructive pulmonary disease (COPD), albuterol and levalbuterol can both be used as relievers to alleviate bronchoconstriction. This study aimed to evaluate levalbuterol and albuterol\'s cost-utility and budget impact in hospitalized patients with COPD.
UNASSIGNED: A cost-utility analysis was used to evaluate the impact on the costs of nebulized levalbuterol verse albuterol in hospitalized patients with COPD. The decision tree model was employed to estimate the incremental cost per quality-adjusted life year in the admission setting. A budget impact model was used to examine the impact of budget on levalbuterol\'s entry into the Chinese market from the healthcare system\'s perspective. One-way sensitivity and probabilistic sensitivity analyses were performed to test the uncertainty of the parameters.
UNASSIGNED: The cost-utility results showed that levalbuterol saved ¥495.7 ($105.1) per hospitalization, while the budget impact analysis revealed a potential saving of ¥22.3 ($6.8) million in 3 years. The sensitivity analysis indicated that the results were robust to the changes in input parameter values.
UNASSIGNED: Levalbuterol is a cost-saving option for treating hospitalized patients with COPD in China.
Chronic obstructive pulmonary disease (COPD) is a common disease in China, with an increased financial burden over the years. Nebulized albuterol is the most commonly used short-acting beta2-agonist, often regarded as the initial bronchodilator to treat hospitalized COPD patients. Its R-isomer, levalbuterol, entered the Chinese market in 2019. The new intervention always impacts the expenditure of the health system. We built a cost-utility and budget impact model to analyze the difference between albuterol and levalbuterol. The cost-utility results showed that levalbuterol saved ¥495.7 ($105.1) per hospitalization compared with albuterol, while the budget impact analysis revealed a potential saving of ¥22.3 ($6.8) million in 3 years.

BACKGROUND: Exocarpium Citri Grandis (Huajuhong) is an authentic Chinese materia medica with excellent curative effects on relieving cough and reducing phlegm, which has been reputed as \"Southern Ginseng\" in China for a long history.
OBJECTIVE: To establish a sequential grade evaluation method with strong operability and controllable quality for Huajuhong decoction pieces.
METHODS: (1) Indicators of ingredients and bio-effects were predicted by network pharmacology, and the potential pharmacodynamic ingredients and key targets were analyzed integrating screening results and literatures. (2) 45 batches of Huajuhong decoction pieces from different producing areas were collected and graded by original plant, planting place, and harvesting time. The chemical indicators determination of Huajuhong decoction pieces was conducted by Ultra Performance Liquid Chromatography (UPLC). (3) 112 rats with idiopathic pulmonary fibrosis (IPF) model were used to evaluated the efficacy within graded groups.
RESULTS: (1) There are 22 key targets corresponding to 20 potential ingredients related to immunity and inflammation pathways for Huajuhong. Naringin and rhoifolin were chosen as the chemical indicators, and IL-6, IL-8, MCP-1, MIP-1α, TNF-α, TGF-β1 were selected as bio-indicators for different grades of Huajuhong decoction pieces. (2) The contents of the naringin and rhoifolin can reflect the quality of different grades of Huajuhong decoction pieces. (3) The efficacy of different grades of Huajuhong decoction pieces can delay the progression of IPF in varying degrees via the selected bio-indicators\' pathways.
CONCLUSIONS: This sequential grading evaluation method is an attempt to apply systems pharmacology which integrates network pharmacology, quantitative chemical and experiments on animals to the classification of TCM decoction pieces. Combining the concepts of traditional theory and modern technology to explain the complex grading mechanism of TCM decoction pieces is worth popularizing and applying.

Rickettsia species are obligate intracellular Gram-negative bacteria that can infect a wide range of vertebrate hosts, including humans, through arthropod vectors such as Ixodid ticks. These ticks are a threat to humans and animals because they are the primary vectors or reservoirs for rickettsiae, which is of public health importance. In this study, we report the identification and percent of positive of Rickettsia spp. in ticks collected from Cangxi County, Southwest China. Haemaphysalis longicornis comprised 48.4% of the 188 ticks collected followed by Haemaphysalis flava (29.3%), H. doenitzi (12.2%), and Haemaphysalis hystricis (10.1%). A total of 63 (33.5%) ticks were positive with Rickettsia spp., with 48 (57%) of those being H. longicornis and 15 (27.3%) being H. flava. The other two tick species, however, did not have any ticks positive for rickettsial DNA. In addition, two different Rickettsia spp. were identified using gltA and ompA as molecular markers. The sequence of Rickettsia sp. infecting H. longicornis ticks was found to be identical to the Rickettsia sequences from Northeastern China and Japan (KF728367, AB516964). Phylogenetic analyses using these molecular markers support the notion that Rickettsia species from H. flava is the most close to a member of the Candidatus Rickettsia gannanii subgroup. The high percentage of Rickettsia positive in this Southwest China region suggests potential public health threat in the future and warrants to be monitored.

In places like China, an ageing population coupled with changes in living standards and increases in disposable income, imply a shift of the demand for health-related goods and services which is likely to affect the whole organization of the industries that supply such goods and services at the global level. One of the industries most likely to be affected is the pharmaceutical sector. In the early 2000s China was already the second largest global producer of pharmaceutical ingredients. The pharmaceutical sector has become one of the most important industries promoted by the Chinese government and Five-Year Plan of China\'s Strategic Emerging Sectors, mergers and acquisition (M&A) activity has been the key strategy to restructure the sector and increase its competitiveness. This paper firstly provides an updated picture of the evolution of M&As in the pharmaceutical sector, compared to other sectors, in China in the period 2005-2013. Secondly, we develop a composite indicator to measure the industrial performance of all Chinese industrial sectors over time, which allows us to assess the performance of the pharmaceutical industry compared to that of other sectors of the Chinese economy. Finally, we develop and estimate an empirical model that tests the relationship between the number of M&A in a sector and its performance, with a particular focus on the pharmaceutical case. The results offer some initial evidence of positive effects from the process of restructuring of the pharmaceutical sector in China.

To investigate the effect of oleanolic acid (OA) on the differentiation of neural stem cells (NSCs) induced by A[Formula: see text] via regulating the JAK/STAT signaling pathway, a neurotoxicity cell model involving the induction of NSCs by soluble A[Formula: see text] (5 [Formula: see text]M) was used. The WST-1 method and immunofluorescence tests were used respectively to detect the activity of cell model and the expression of GFAP[Formula: see text]/DAPI and Tubulin[Formula: see text]/DAPI. Western blotting and real-time PCR analyses were used to observe the effects of OA on NSCs differentiation by examining key targets of the JAK/STAT signal transduction pathway. Compared with normal NSCs, A[Formula: see text]-induced NSCs had down-regulated expression of Ngn1 and up-regulated STAT3 expression and phosphorylation, and inhibited neuronal differentiation. OA treatment effectively inhibited the A[Formula: see text]-induced activation of JAK/STAT signaling, with a significant increase in Ngn1 expression and a significant decrease in p-STAT3/STAT3. These results indicate that OA could inhibit the excessive differentiation of NSCs into astrocytes by down-regulating JAK/STAT signaling which might retard the progress of AD.

Chlorophyll content, one of the most important physiological parameters related to plant photosynthesis, is usually used to predict yield potential. To map the quantitative trait loci (QTLs) underlying the chlorophyll content of rice leaves, a double haploid (DH) population was developed from an indica/japonica (Zhenshan 97/Wuyujing 2) crossing and two backcross populations were established subsequently by backcrossing DH lines with each of their parents. The contents of chlorophyll a and chlorophyll b were determined by using a spectrophotometer to directly measure the leaf chlorophyll extracts. To determine the leaf chlorophyll retention along with maturation, all measurements were performed on the day of heading and were repeated 30 days later. A total of 60 QTLs were resolved for all the traits using these three populations. These QTLs were distributed on 10 rice chromosomes, except chromosomes 5 and 10; the closer the traits, the more clustering of the QTLs residing on common rice chromosomal regions. In general, the majority of QTLs that specify chlorophyll a content also play a role in determining chlorophyll b content. Strangely, chlorophyll content in this study was found mostly to be lacking or to have a negative correlation with yield. In both backcross F1 populations, overdominant (or underdominant) loci were more important than complete or partially dominant loci for main-effect QTLs and epistatic QTLs, thereby supporting previous findings that overdominant effects are the primary genetic basis for depression in inbreeding and heterosis in rice.

BACKGROUND: Mucolipidosis type III gamma (MLIII gamma) is an autosomal recessive disease caused by a mutation in the GNPTG gene, which encodes the γ subunit of the N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase). This protein plays a key role in the transport of lysosomal hydrolases to the lysosome.
METHODS: Three Chinese children with typical skeletal abnormalities of MLIII were identified, who were from unrelated consanguineous families. After obtaining informed consent, genomic DNA was isolated from the patients and their parents. Direct sequencing of the GNPTG and GNPTAB genes was performed using standard PCR reactions.
RESULTS: The three probands showed clinical features typical of MLIII gamma, such as joint stiffness and vertebral scoliosis without coarsened facial features. Mutation analysis of the GNPTG gene showed that three novel mutations were identified, two in exon seven [c.425G>A (p.Cys142Val)] and [c.515dupC (p.His172Profs27X)], and one in exon eight [c.609+1G>C]. Their parents were determined to be heterozygous carriers when compared to the reference sequence in GenBank on NCBI.
CONCLUSIONS: Mutation of the GNPTG gene is the cause of MLIII gamma in our patients. Our findings expand the mutation spectrum of the GNPTG gene and extend the knowledge of the phenotype-genotype correlation of the disease.

Ototoxicity induced by aminoglycoside antibiotics appears to occur both in hair cells (HCs) and the cochlear nerves that innervate them. Although HC loss can be easily quantified, neuronal lesions are difficult to quantify because two types of afferent dendrites and two types of efferent axons are tangled beneath the hair cells. In the present study, ototoxicity was induced by gentamicin in combination with the diuretic agent furosemide. Neuronal lesions were quantified in cochlear whole-mount preparations combined with microsections across the habenular perforate (HP) openings to achieve a clear picture of the topographic relationship between neuronal damage and HC loss. Multiple immunostaining methods were employed to differentiate the two types of afferent dendrites and two types of efferent axons. The results show that co-administration of gentamicin and furosemide resulted in a typical dynamic pattern of HC loss that spread from the basal turn to the outer hair cells to the apex and inner hair cells, depending on the dose and survival time after drug administration. Lesions of the innervation appeared to occur at two stages. At the early stage (2-4 days), the loss of labeling of the two types of afferent dendrites was more obvious than the loss of labeled efferent axons. At the late stage (2-4 weeks), the loss of labeled efferent axons was more rapid. In the high-dose gentamicin group, the loss of outer HCs was congruent with afferent dendrite loss at the early stage and efferent axon loss at the late stage. In the low-dose gentamicin group, the loss of labeling for cochlear innervation was more severe and widespread. Thus, we hypothesize that the gentamicin-induced damage to cochlear innervation occurs independently of hair cell loss.

The Piwi genes have an important role in stem cell development, gametogenesis and RNA interference in diverse organisms. So far, most of the studies have focused on the function of Piwis in vertebrates, but their function during spermiogenesis in invertebrates still remains largely unclear. In order to investigate the function of Piwis during spermiogenesis in the crab Portunus trituberculatus, we use RT-PCR and RACE to identify three Piwi complete cDNA sequences from the total RNA of the testis in P. trituberculatus. The deduced amino acid sequences of P. trituberculatus Piwi-1, Piwi-2 and Piwi-3 showed that each contains a well-conserved PAZ domain and PIWI domain. RT-PCR analyzed the tissue expression pattern of P. trituberculatus Piwi-1, Piwi-2 and Piwi-3 in the testis, heart, muscle, hepatopancreas and gill. All of the Piwis are found in germ cells of adult testis in P. trituberculatus by in situ hybridization, suggesting that these genes may play function during spermiogenesis in this species.