Individualized Use of 6-Mercaptopurine in Chinese Children with ALL: A Multicenter Randomized Controlled Trial.

Continuous 6-mercaptopurine (6-MP) dose titration is necessary because of its narrow therapeutic index and frequently encountered dose-limiting hematopoietic toxicity. However, evidence-based guidelines for gene-based 6-MP dosing have not been established for Chinese children with acute lymphoblastic leukemia (ALL). This multicenter, randomized, open-label, active-controlled clinical trial randomly assigned Chinese children with low- or intermediate-risk ALL in a 1:1 ratio to receive TPMT-NUDT15 gene-based dosing of 6-MP (N = 44, 10 to 50 mg/m2 /day) or standard dosing (N = 44, 50 mg/m2 /day) during maintenance therapy. The primary end point was the incidence of 6-MP myelosuppression in both groups. Secondary end points included frequencies of 6-MP hepatotoxicity, duration of myelosuppression and leukopenia, event-free survival, and steady-state concentrations of active metabolites (6-thioguaninenucleotides and 6-methylmercaptopurine nucleotides) in erythrocytes. A 2.2-fold decrease in myelosuppression, the primary end point, was observed in the gene-based-dose group using ~ 50% of the standard initial 6-MP dose (odds ratio, 0.26, 95% confidence interval, 0.11 to 0.64, P = 0.003). Patients in the gene-based-dose group had a significantly lower risk of developing thiopurine-induced myelosuppression and leukopenia (P = 0.015 and P = 0.022, respectively). No significant differences were observed in the secondary end points of the incidence of hepatotoxicity and steady-state concentrations of active metabolites in erythrocytes between the two groups. TPMT- and NUDT15-based dosing of 6-MP will significantly contribute toward further reducing the incidence of leukopenia in Chinese children with ALL. This trial is registered at www.clinicaltrial.gov as #NCT04228393.

Enantioselective effect of the chiral fungicide tebuconazole on the microbiota community and antibiotic resistance genes in the soil and earthworm gut.

Tebuconazole, consisting of two enantiomers, has a high detectable rate in the soil. The residue of tebuconazole in the soil may cause risk to microbiota community. Antibiotic resistance genes (ARGs) are considered as emerging environmental contaminants, and they can be transferred vertically and horizontally between microbiota community in the soil. Until now, the enantioselective effect of tebuconazole on the microbiota community and ARGs in the soil and earthworm gut has remained largely unknown. Tebuconazole enantiomers showed different bioconcentration behaviors in earthworms. The relative abundances of bacteria belonging to Actinobacteriota, Crenarchaeota and Chloroflexi in R-(-)-tebuconazole-treated soil were higher than those in S-(+)-tebuconazole-treated soil at same concentrations. In the earthworm gut, bacteria belonging to Proteobacteria and Bacteroidota exhibited different relative abundances between the S-(+)-tebuconazole and R-(-)-tebuconazole treatments. The numbers and abundances of ARGs in the soil treated with fungicides were higher than those in the control. In earthworm gut, the diversities of ARGs in all treatments were higher than that in the control, and the relative abundances of Aminoglycoside, Chloramphenicol, Multidrug resistance genes and mobile genetic elements (MGEs) in R-(-)-tebuconazole-treated earthworm gut were higher than those in S-(+)-tebuconazole-treated earthworm gut. Most of ARGs showed a significantly positive correlation with MGEs. Based on network analysis, many ARGs may be carried by bacteria belonging to Bacteroidota and Proteobacteria. These results provide valuable information for understanding the enantioselective effect of tebuconazole on the microbiota community and ARGs.

Engineering Cu/NiCu LDH Heterostructure Nanosheet Arrays for Highly-Efficient Water Oxidation.

The development of stable and efficient electrocatalysts for oxygen evolution reaction is of great significance for electro-catalytic water splitting. Bimetallic layered double hydroxides (LDHs) are promising OER catalysts, in which NiCu LDH has excellent stability compared with the most robust NiFe LDH, but the OER activity is not satisfactory. Here, we designed a NiCu LDH heterostructure electrocatalyst (Cu/NiCu LDH) modified by Cu nanoparticles which has excellent activity and stability. The Cu/NiCu LDH electrocatalyst only needs a low over-potential of 206 mV and a low Tafel slope of 86.9 mV dec-1 at a current density of 10 mA cm-2 and maintains for 70 h at a high current density of 100 mA cm-2 in 1M KOH. X-ray photoelectron spectroscopy (XPS) showed that there was a strong electronic interaction between Cu nanoparticles and NiCu LDH. Density functional theory (DFT) calculations show that the electronic coupling between Cu nanoparticles and NiCu LDH can effectively improve the intrinsic OER activity by optimizing the conductivity and the adsorption energy of oxygen-containing intermediates.

Soil conditions and the plant microbiome boost the accumulation of monoterpenes in the fruit of Citrus reticulata 'Chachi'.

BACKGROUND: The medicinal material quality of Citrus reticulata 'Chachi' differs depending on the bioactive components influenced by the planting area. Environmental factors, such as soil nutrients, the plant-associated microbiome and climatic conditions, play important roles in the accumulation of bioactive components in citrus. However, how these environmental factors mediate the production of bioactive components of medicinal plants remains understudied. RESULTS: Here, a multi-omics approach was used to clarify the role of environmental factors such as soil nutrients and the root-associated microbiome on the accumulation of monoterpenes in the peel of C. reticulata 'Chachi' procured from core (geo-authentic product region) and non-core (non-geo-authentic product region) geographical regions. The soil environment (high salinity, Mg, Mn and K) enhanced the monoterpene content by promoting the expression of salt stress-responsive genes and terpene backbone synthase in the host plants from the core region. The microbial effects on the monoterpene accumulation of citrus from the core region were further verified by synthetic community (SynCom) experiments. Rhizosphere microorganisms activated terpene synthesis and promoted monoterpene accumulation through interactions with the host immune system. Endophyte microorganisms derived from soil with the potential for terpene synthesis might enhance monoterpene accumulation in citrus by providing precursors of monoterpenes. CONCLUSIONS: Overall, this study demonstrated that both soil properties and the soil microbiome impacted monoterpene production in citrus peel, thus providing an essential basis for increasing fruit quality via reasonable fertilization and precision microbiota management. Video Abstract.

A Review of Filtration Performance of Protective Masks.

Masks are essential and effective small protective devices used to protect the general public against infections such as COVID-19. However, available systematic reviews and summaries on the filtration performance of masks are lacking. Therefore, in order to investigate the filtration performance of masks, filtration mechanisms, mask characteristics, and the relationships between influencing factors and protective performance were first analyzed through mask evaluations. The summary of filtration mechanisms and mask characteristics provides readers with a clear and easy-to-understand theoretical cognition. Then, a detailed analysis of influencing factors and the relationships between the influencing factors and filtration performance is presented in. The influence of the aerosol size and type on filtration performance is nonlinear and nonconstant, and filtration efficiency decreases with an increase in the gas flow rate; moreover, fitness plays a decisive role in the protective effects of masks. It is recommended that the public should wear surgical masks to prevent COVID-19 infection in low-risk and non-densely populated areas. Future research should focus on fitness tests, and the formulation of standards should also be accelerated. This paper provides a systematic review that will be helpful for the design of masks and public health in the future.

Valorization of Livestock Keratin Waste: Application in Agricultural Fields.

Livestock keratin waste is a rich source of protein. However, the unique structure of livestock keratin waste makes its valorization a great challenge. This paper reviews the main methods for the valorization of livestock keratin waste, which include chemical, biological, and other novel methods, and summarizes the main agricultural applications of keratin-based material. Livestock keratin waste is mainly used as animal feed and fertilizer. However, it has promising potential for biosorbents and in other fields. In the future, researchers should focus on the biological extraction and carbonization methods of processing and keratin-based biosorbents for the soil remediation of farmland.

Chan-Lam Reaction and Lewis Acid Promoted 1,3-Rearrangement of N-O Bonds to Prepare N-(2-Hydroxyaryl)pyridin-2-ones.

We describe the difunctionalization of arylboronic acids to prepare various N-(2-hydroxyaryl)pyridin-2-ones in good yields using N-hydroxypyridin-2-ones as the oxygen and nitrogen sources through a copper(II)-catalyzed Chan-Lam reaction and subsequent BF3-promoted selective 1,3-rearrangement of N-O bond in a one-pot procedure. Mechanistic studies reveal that the 1,3-rearrangement selectivity is controlled by the formation of the key aryloxypyridinium salt. The obtained products are easily converted to various useful pyridin-2-one scaffolds.

Seasonal and vegetational variations of culturable bacteria concentrations in air from urban forest parks: a case study in Hunan, China.

It is important to investigate the airborne bacterial air quality in urban forest parks as tree bacteriostasis practices are being increasingly advocated as measures to improve the air quality and public health in urban green spaces around the world. The aim of the study was to quantitatively investigate airborne culturable bacteria (ACB) concentration levels based on field measurements in every season in five selected forest communities and the uncovered space in an urban forest park, as well as the effects of several factors on the culturability of airborne bacteria. Results suggested that the airborne bacterial levels of all the forest communities reached the clean air quality standard with regard to the airborne bacteria content, with the highest concentration of ACB showing in the uncovered space (1658 ± 1298 CFU/m3) and the lowest showing in the mixed community (907 ± 567 CFU/m3). The temporal distribution analysis showed that the airborne bacteria were mostly concentrated in summer, as well as in the morning and afternoon. The bacteriostatic rates of the mixed community were significantly different with seasonal variation (p < 0.05). Spearman's correlations revealed that the concentration of ACB was significantly positively correlated with the season, wind speed (WS), temperature (T), ultraviolet light (UV), negative air ion (NAI), and total suspended particles (TSP) (p<0.05) but significantly negatively correlated with the forest community type (p < 0.05). Overall, the selection of tree species plays a key role in shaping the forest structure and improving air quality, and the urban forest highlights key priorities for future efforts toward a cleaner, healthier, and more diverse regional forest environment.

Overexpression of Twist1 in vascular endothelial cells promotes pathological retinal angiogenesis in mice.

Retinal angiogenesis is a critical process for normal retinal function. However, uncontrolled angiogenesis can lead to pathological neovascularization (NV), which is closely related to most irreversible blindness-causing retinal diseases. Understanding the molecular basis behind pathological NV is important for the treatment of related diseases. Twist-related protein 1 (TWIST1) is a well-known transcription factor and principal inducer of epithelial-mesenchymal transition (EMT) in many human cancers. Our previous study showed that Twist1 expression is elevated in pathological retinal NV. To date, however, the role of TWIST1 in retinal pathological angiogenesis remains to be elucidated. To study the role of TWIST1 in pathological retinal NV and identify specific molecular targets for antagonizing pathological NV, we generated an inducible vascular endothelial cell (EC)-specific Twist1 transgenic mouse model ( Tg-Twist1 iEC+ ). Whole-mount retinas from Tg-Twist1 iEC+ mice showed retarded vascular progression and increased vascular density in the front end of the growing retinal vasculature, as well as aneurysm-like pathological retinal NV. Furthermore, overexpression of Twist1 in the ECs promoted cell proliferation but disturbed cell polarity, thus leading to uncontrolled retinal angiogenesis. TWIST1 promoted pathological NV by activating the Wnt/ß-catenin signaling pathway and inducing the expression of NV formation-related genes, thereby acting as a 'valve' in the regulation of pathological angiogenesis. This study identified the critical role of TWIST1 in retinal pathological NV, thus providing a potential therapeutic target for pathological NV.

Biodegradation mechanism of chloramphenicol by Aeromonas media SZW3 and genome analysis.

The overuse of chloramphenicol (CAP) due to its low price is detrimental to ecological safety and human health. An earthworm gut content dwelling bacterium, Aeromonas media SZW3, was isolated with capability of CAP biodegradation, and the CAP degradation efficiency reached 55.86% at day 1 and 67.28% at day 6. CAP biodegradation kinetics and characteristic of strain SZW3 determined the factors that affect CAP biodegradation. Thirteen possible biodegradation products were identified, including three novel biodegradation products (CP1, CP2 and CP3), and three potential biodegradation pathway were proposed. Biodegradation reactions include amide bond hydrolysis, nitro group reduction, acetylation, aminoacetylation, dechlorination and oxidation. Genome analysis suggested that the coding gene of RarD (CAP resistance permease), CAP O-acetyltransferase, nitroreductase and haloalkane dehalogenase may be responsible for CAP biodegradation. The proposed complete biodegradation pathway and genome analysis by strain SZW3 provide us new insight of the transformation route and fate of CAP in the environment.

Mechanisms of the enhanced DDT removal from soils by earthworms: Identification of DDT degraders in drilosphere and non-drilosphere matrices.

The remediation of soil contaminated by 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) remains an important issue in environmental research. Although our previous studies demonstrated that earthworms could enhance the degradation of DDT in soils, the underlying mechanisms and microorganisms involved in these transformation processes are still not clear. Here we studied the transformation of DDT in sterilized/non-sterilized drilosphere and non-drilosphere matrices and identified DDT degraders using the technique of DNA-stable isotope probing. The results show that DDT degradation in non-sterilized drilosphere was quicker than that in their non-drilosphere counterparts. Earthworms enhance DDT removal mainly by improving soil properties, thus stimulating indigenous microorganisms rather than abiotic degradation or tissue accumulating. Ten new genera, including Streptomyces, Streptacidiphilus, Dermacoccus, Brevibacterium, Bacillus, Virgibacillus, were identified as DDT ring cleavage degrading bacteria in the five matrices tested. Bacillus and Dermacoccus may also play vital roles in the dechlorination of DDTs as they were highly enriched during the incubations. The results of this study provide robust evidence for the application of earthworms in remediating soils polluted with DDT and highlight the importance of using combinations of cultivation-independent techniques together with process-based measurements to examine the function of microbes degrading organic pollutants in drilosphere matrices.

Facultative methanotrophs - diversity, genetics, molecular ecology and biotechnological potential: a mini-review.

Methane-oxidizing bacteria (methanotrophs) play a vital role in reducing atmospheric methane emissions, and hence mitigating their potent global warming effects. A significant proportion of the methane released is thermogenic natural gas, containing associated short-chain alkanes as well as methane. It was one hundred years following the description of methanotrophs that facultative strains were discovered and validly described. These can use some multi-carbon compounds in addition to methane, often small organic acids, such as acetate, or ethanol, although Methylocella strains can also use short-chain alkanes, presumably deriving a competitive advantage from this metabolic versatility. Here, we review the diversity and molecular ecology of facultative methanotrophs. We discuss the genetic potential of the known strains and outline the consequent benefits they may obtain. Finally, we review the biotechnological promise of these fascinating microbes.

Maternal valproic acid exposure leads to neurogenesis defects and autism-like behaviors in non-human primates.

Despite the substantial progress made in identifying genetic defects in autism spectrum disorder (ASD), the etiology for majority of ASD individuals remains elusive. Maternal exposure to valproic acid (VPA), a commonly prescribed antiepileptic drug during pregnancy in human, has long been considered a risk factor to contribute to ASD susceptibility in offspring from epidemiological studies in humans. The similar exposures in murine models have provided tentative evidence to support the finding from human epidemiology. However, the apparent difference between rodent and human poses a significant challenge to extrapolate the findings from rodent models to humans. Here we report for the first time the neurodevelopmental and behavioral outcomes of maternal VPA exposure in non-human primates. Monkey offspring from the early maternal VPA exposure have significantly reduced NeuN-positive mature neurons in prefrontal cortex (PFC) and cerebellum and the Ki67-positive proliferating neuronal precursors in the cerebellar external granular layer, but increased GFAP-positive astrocytes in PFC. Transcriptome analyses revealed that maternal VPA exposure disrupted the expression of genes associated with neurodevelopment in embryonic brain in offspring. VPA-exposed juvenile offspring have variable presentations of impaired social interaction, pronounced stereotypies, and more attention on nonsocial stimuli by eye tracking analysis. Our findings in non-human primates provide the best evidence so far to support causal link between maternal VPA exposure and neurodevelopmental defects and ASD susceptibility in humans.

Low interferon-gamma release in response to phytohemagglutinin predicts the high severity of diseases.

A clinically useful immune biomarker could potentially assist clinicians in their decision making. We stimulated T-cell proliferation to secret interferon gamma (IFN-γ) by phytohemagglutinin, and then measured the production of IFN-γ (mitogen value [M value]). We aimed to determine the relationship between the M value, clinical severity, and outcomes of diseases.In all, 484 patients admitted to intensive care units were enrolled in this retrospective study. The Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were collected within the first 24 hours. M value, C-reaction protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), and routine blood tests were analyzed and collected during the study.When APACHE II scores were greater than 15 and M values were less than 6, the hospital mortality rose in a straight line. There was an inverse correlation between APACHE II score and M value (rs = -0.212, P < .001). There was a positive correlation between M value and lymphocyte numbers (b' = 0.249, P < .001); however, there was an inverse correlation between M value and WBC (b' = -0.230, P < .001), and ESR (b' = -0.100, P = .029). Neurological diseases had the greatest influence on APACHE II scores (b' = 10.356, P < .001), whereas respiratory diseases had the greatest influence on M value (b' = 1.933, P < .001). Furthermore, in the respiratory system, severe pneumonia had a greater influence on M value. Taking the APACHE II score as the gold standard, the area under the curve of M was 0.632 (95% confidence interval [CI] 0.575-0.690, P < .001), PCT was 0.647 (95% CI 0.589-0.705, P < .001), CRP was 0.570 (95% CI 0.511-0.629, P = .022), and ESR was 0.553 (95% CI 0.494-0.612, P = .078). Divided by M value = 5, the positive predictive value of the M value is 37.22% (115/309) and negative predictive value is 75.43% (132/175).The results show that the M values, PCT, and CRP were better than ESR to predict the severity of diseases. The number and proportion of lymphocytes also affected the result of the M value. To a certain extent, the M value may be a clinically useful immune biomarker, which may help clinicians objectively evaluate the severity of diseases, especially in the respiratory system.

A Thermoelectric-Heat-Pump Employed Active Control Strategy for the Dynamic Cooling Ability Distribution of Liquid Cooling System for the Space Station's Main Power-Cell-Arrays.

A proper operating temperature range and an acceptable temperature uniformity are extremely essential for the efficient and safe operation of the Li-ion battery array, which is an important power source of space stations. The single-phase fluid loop is one of the effective approaches for the thermal management of the battery. Due to the limitation that once the structure of the cold plate (CP) is determined, it is difficult to adjust the cooling ability of different locations of the CP dynamically, this may lead to a large temperature difference of the battery array that is attached to the different locations of the CP. This paper presents a micro-channel CP integrated with a thermoelectric heat pump (THP) in order to achieve the dynamic adjustment of the cooling ability of different locations of the CP. The THP functions to balance the heat transfer within the CP, which transports the heat of the high-temperature region to the low-temperature region by regulating the THP current, where a better temperature uniformity of the CP can be achieved. A lumped-parameter model for the proposed system is established to examine the effects of the thermal load and electric current on the dynamic thermal characteristics. In addition, three different thermal control algorithms (basic PID, fuzzy-PID, and BP-PID) are explored to examine the CP's temperature uniformity performance by adapting the electric current of the THP. The results demonstrate that the temperature difference of the focused CP can be declined by 1.8 K with the assistance of the THP. The proposed fuzzy-PID controller and BP-PID controller present much better performances than that provided by the basic PID controller in terms of overshoot, response time, and steady state error. Such an innovative arrangement will enhance the CP's dynamic cooling ability distribution effectively, and thus improve the temperature uniformity and operating reliability of the Li-ion space battery array further.

Removal of persistent DDT residues from soils by earthworms: A mechanistic study.

Earthworms have been reported to enhance DDT (1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane) removal from soils, but the mechanism underlying is still poorly understood. This study therefore worked on the links between DDT transformation in drilosphere and non-drilosphere matrices and the properties of these matrices in sterile and non-sterile soil columns with and without earthworms to reveal related mechanisms. The results show that earthworms shortened the half-time of DDT in soils from over 14 weeks to about 8 weeks; DDT residues were lower (p < 0.05) and its transformation products were higher (p < 0.05) in drilosphere matrixes than those in their non-drilosphere counterparts; DDD and DDMU was higher (p < 0.05) in the gut, and DDE was higher (p < 0.05) in the burrow; and the bioaccumulation of DDT in earthworm tissues only contributed less than 0.03% to the DDT removal enhanced by earthworms. The results further demonstrate that drilosphere is the hotspot of soil DDT transformation with oxidative degradation dominant in the burrow and reductive dechlorination in the gut, and earthworms enhanced DDT removal mainly by digesting and promoting the microbial degradation of DDT by indigenous microorganisms via improving soil properties. Knowledge of the mechanisms of DDT transformation by earthworms will support the use of earthworms in remediating DDT-contaminated soils.

Nitrogen inputs are more important than denitrifier abundances in controlling denitrification-derived N2O emission from both urban and agricultural soils.

Cities are increasingly being recognized as important contributors in global warming, for example by increasing atmospheric nitrous oxide (N2O). However, urban ecosystems remain poorly understood due to their functional complexity. Further, few studies have documented the microbial processes governing the N2O emissions from urban soils. Here, a field study was performed to assess in situ N2O emissions in an urban and agricultural soil located in Xiamen, China. The mechanisms underlying the difference in N2O emission patterns in both soils were further explored in an incubation experiment. Field investigations showed that N2O emission (3.5-19.0 µg N2O-N m-2 h-1) from the urban soil was significantly lower than that from the agricultural soil (25.4-18,502.3 µg N2O-N m-2 h-1). Incubation experiments showed that the urban soil initially emitted lower denitrification-derived N2O because of the lower nirS (encoding nitrite reductases) abundances, whereas overall N2O accumulation during the incubation was mainly controlled by the initial nitrate content in soil. Nitrate addition in a short period (5 days) did not change the total bacterial and denitrifier abundances or the soil bacterial community composition, but significantly altered the relative distribution of some key genera capable of denitrification. Although the urban soil exhibited lower N2O emission than its agricultural counterpart in this study, the expanding urban green areas should be taken into account when building N2O emission reduction targets.

Earthworms stimulate nitrogen transformation in an acidic soil under different Cd contamination.

In acidic Cd-contaminated soils, soil nitrogen conversion is inhibited and usually block nitrogen supply for plants. Earthworms are well known for improving soil properties and regulating various soil biogeochemical processes including nitrogen cycling. To figure out the effect and mechanisms of earthworms on soil nitrogen transformation in Cd-contaminated soil, ten treatments with and without A. robustus in five soil Cd concentration gradients were established. The tolerant concentration of A. robustus to Cd in the acidic soil is about 6 mg kg-1. The potential ammonia oxidation of the acidic soils was very low, ranging from 0.05 to 0.1 µg NO2--N g-1 d-1. Although AOA was more abundant in the acidic soil than AOB, AOA was inhibited by Cd pollution, while AOB showed some increase under Cd-stress. AOA may play a dominant role in ammonia oxidation in acidic soil, but the recovery of nitrification in Cd-contaminated acidic soil was probably due to the effect of AOB. Earthworms significantly increased soil pH, DOC, ammonium and PAO, thus promoted soil ammonification and potential nitrification, but had no significant effect on soil net nitrification. Correlation analysis results demonstrate that earthworms may promote soil PAO by increasing soil pH, NH4+-N content, and AOB abundance. This study could provide a theoretical basis for solving the problem of nitrogen-cycling-functional degradation and nitrogen supply in the process of phytoremediation of heavy metals-contaminated soils.

Liuwei Dihuang Pill () Treats Postmenopausal Osteoporosis with Shen (Kidney) Yin Deficiency via Janus Kinase/Signal Transducer and Activator of Transcription Signal Pathway by Up-regulating Cardiotrophin-Like Cytokine Factor 1 Expression.

OBJECTIVES: To investigate the mechanism of Liuwei Dihuang Pill (, LDP) in treating postmenopausal osteoporosis (PMOP) with Shen (Kidney) yin deficiency. METHODS: In this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group (Group A), PMOP Shen-yang deficiency group (Group B), PMOP without Shen deficiency group (Group C), and control group (Group N). Real-time polymerase chain reaction (RT-PCR) and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 (CLCF1), ankyrin repeat and SOCS box containing 1 (ASB1), and prokineticin 2 (PROK2) genes and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. RESULTS: The mRNA (P<0.05) and protein (P<0.01) expression levels of the CLCF1 gene in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gene were obviously up-regulated (P<0.01). After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated (both P<0.01), and the average bone density of the top femur had significantly increased (P<0.05). In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3. CONCLUSIONS: The CLCF1 gene is an important gene associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gene expression and activation of the JAK/STAT signaling pathway.