"Sinew prescription correspondence" is the principle of selecting prescriptions for channel sinew diseases. On the basis of the theory of syndrome differentiation and treatment， the pulse manifestation corresponds to the channel sinew syndrome， which can improve the flexibility and standardization of clinical prescriptions. From the perspective of systematic dialectical sphygmology， this paper explains the dialectical relationship between channel sinew theory and pulse body elements， pulse wall elements， pulse elements and blood flow elements， and clarifies the internal relationship between pulse manifestation and prescriptions at the level of channel sinew disease. The prescription is derived from the method， while the method is established with the syndrome， and the prescription is unified by the method. According to the theory of "sinew prescription correspondence"， the treatment ideas of channel sinew diseases were analyzed from the perspective of channel sinew distribution， functional characteristics and structural changes. On this basis， the diagnosis of channel sinew disease and the application of prescriptions are expanded， and the research on the internal treatment and diagnosis mode of "pulse manifestation-channel sinew-zang fu （脏腑）" is prospected， so as to expand the differentiation and treatment methods of channel sinew theory.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

Formate is an important solar fuel, with large application potential in bioconversion. Especially, the win-win collaboration is achieved when formate is applied to the cultivation of microalgae, which combines the advantages from both artificial and natural photosynthesis. However, the inhibition of formate on the photosynthetic electron transport hinders the application of formate at high concentrations. The engineering or directed evolution of the regulation pathway is a case-by-case and time-consuming strategy. Here, we developed a new strategy by introducing a Stenotrophomonas sp. strain which was isolated and identified from the long-term self-evolution process of Chlamydomonas reinhardtii for adapting to high concentrations of formate. The co-culture with the strain or the fermentation broth relieved the inhibition of formate (50 mmol/L) on C. reinhardtii and promoted the growth of the microalga. Especially, the protein content increased significantly to nearly 50% of the dried weight. In addition, the co-culture also benefited the growth of both Chlorella pyrenoidesa and Synechocystis sp. PCC 6803 exposed to formate, which indicated broader applicability of this strategy. This strategy provides the opportunity to overcome the bottleneck in the formate-mediated artificial-natural hybrid photosynthesis and to aid the development of technologies for solar energy-driven production of bulk biomass, including proteins, by carbon dioxide reduction.
Photosynthesis/physiology* ; Formates/pharmacology* ; Stenotrophomonas/growth & development* ; Microalgae/metabolism* ; Chlamydomonas reinhardtii/growth & development*

Objective:To discuss the role of changes of serum total bile acid(TBA)levels induced by long-term high-fat diet in the occurrence of supraventricular arrhythmia(SVA)in the apolipoprotein E knockout(ApoE-/-)mice,and to clarify its mechanism.Methods:Twenty ApoE-/-mice were randomly divided into normal diet group and high-fat diet(HFD)group(n=10);after 20 weeks of feeding,surface electrocardiogram was used to detect cardiac electrophysiology of the mice in various groups;echocardiography was used to detect cardiac systolic function and structure in the mice in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of blood lipids,total bile acid(TBA)and inflammatory factors in the mice in various groups;hematoxylin-eosin(HE)staining was used to detect cardiac inflammatory response in the mice in various groups;Masson staining was used to observe myocardial fibrosis degree in the mice in various groups.Results:Compared with normal diet group,4 cases of junctional premature beat(JPB)/junctional tachycardia(JT),1 case of premature atrial contraction(PAC)and 1 case of premature ventricular contraction(PVC)were found in HFD group,while only 1 case of JPB/JT and 1 case of PAC were found in normal diet group.Compared with normal diet group,the heart rate of the mice in HFD group was significantly decreased(P<0.05);the QRS and QT intervals were significantly prolonged(P<0.05);the ejection fraction(EF)and fractional shortening(FS)were significantly decreased(P<0.05);the end-diastolic volume(EDV)was increased(P<0.05),but there was no significant difference in end-systolic volume(ESV)between groups(P>0.05);the left ventricular internal diameter at end-diastole(LVIDd)and left ventricular internal diameter at end-systole(LVIDs)were significantly increased(P<0.05).There were no significant differences in plasma total cholesterol(TC),triglyceride(TG),high-density lipoprotein(HDL-c)and low-density lipoprotein(LDL-c)levels and body weight between normal diet group and HFD group(P>0.05).Compared with normal diet group,the TBA level of the mice in HFD group was significantly increased(P<0.05).There were no significant differences in interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),monocyte chemoattractant protein-1(MCP-1),and C-X-C motif chemokine ligand 1(CXCL-1)levels between HFD group and normal diet group.Compared with normal diet group,the interleukin-1β(IL-1β)level in HFD group showed an increasing trend,but there was no significant difference between groups(P>0.05).The HE staining results showed that the inflammatory cell infiltration was similar between HFD group and normal diet group.The Masson staining results showed that compared with normal diet group,the fibrosis of the mice in HFD group showed an increasing trend,but there was no significant difference in myocardial fibrosis area between groups(P>0.05).Conclusion:Long-term high-fat diet may increase serum TBA level in ApoE-/-mice,which may induce SVA.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To explore the characteristics and evolutionary features of cognitive impairment and clinical transformation in early-stage Parkinson′s disease (PD) patients.Methods:Based on the cohort of patients with primary unmedicated PD admitted to the Parkinson′s Specialized Outpatient Clinic of Affiliated Brain Hospital of Nanjing Medical University from November 2018 to July 2022, follow-up was conducted for PD patients who completed the baseline assessment and had a follow-up time of 1.5 years or more, and a total of 87 patients finally completed the follow-up and were included in the study. At follow-up, the 87 patients were divided into a cognitively impaired group ( n=36) and a cognitively normal group ( n=51) according to the norm proposed by Professor Jia Jianping and colleagues in 2011 for the Chinese elderly population. Differences in baseline clinical characteristics between the 2 groups were compared, and binary Logistic regression analysis was used to explore risk factors for cognitive impairment in PD patients. In addition, transformed grouping according to cognitive assessment results at baseline and follow-up was used to compare differences in patients′ baseline clinical characteristics among the 3 groups: a reversal group [Parkinson′s disease-mild cognitive impairment (PD-MCI), reverting to Parkinson′s disease-cognitively normal (PD-CN); n=15], a non-reversal group (persistent PD-MCI; n=24), and a stable group (stable PD-CN; n=36). Results:Cognitive reversal occurred at follow-up in 36.6% (15/41) of patients with cognitive impairment at baseline, and 21.7% (10/46) of patients with normal cognition at baseline had cognitive impairment at follow-up. At the end of the follow-up, the 87 patients with PD had higher Unified Parkinson′s Disease Rating Scale Ⅱ (UPDRS-II) scores [8 (6, 11)], Unified Parkinson′s Disease Rating Scale Ⅲ (UPDRS-Ⅲ) scores [23 (16, 30)], and Hoehn-Yahr stages [2.0 (1.5, 2.5)] than those at baseline [7(4, 10), 19(14, 25), 1.5(1.0, 2.0)]. The differences were statistically significant ( Z=-2.498, P=0.012; Z=-3.039, P=0.002; Z=-4.436, P<0.001). The cognitively impaired group had lower Montreal Cognitive Assessment scores [22.00(19.00, 23.75)] and fewer years of education [9.00(8.00, 11.75) years] but higher Parkinson′s Disease Non-Motor Symptoms Questionnaire (PD-NMSQ) scores [8.00(5.25, 12.00)] than the cognitively normal group [25.00(24.00, 27.00), 12.00(9.00, 15.00) years, 6.00(3.00, 8.00)], and the differences were statistically significant ( Z=-4.764, P<0.001; Z=-3.016, P=0.003; Z=-3.281, P=0.001). Multivariate Logistic regression showed that years of education ( OR=0.829, 95%CI 0.715-0.960, P=0.012) and PD-NMSQ scores ( OR=1.200, 95%CI 1.040-1.384, P=0.012) were independent predictors of cognitive impairment in patients with PD. There were statistically significant differences among the reversal, non-reversal, and stable groups in years of education ( F=5.366, P=0.010), PD-NMSQ scores ( H=10.795, P=0.005), and UPDRS-Ⅱ scores ( H=6.957, P=0.031). Pairwise comparisons showed lower PD-NMSQ scores [4.00(3.00, 7.00) vs 8.00(6.25, 12.75); Z=-2.989, P=0.003] and lower UPDRS-Ⅱ scores [6.00(3.00, 6.00) vs 7.00(6.00, 10.00); Z=-2.756, P=0.006] in the reversal group than in the non-reversal group, indicating better baseline quality of life in cognitive reversal patients. Conclusions:Low educational level and severe non-motor symptoms were risk factors predicting cognitive impairment in PD patients. Conversely, mild non-motor symptoms with high quality of life (lower UPDRS-Ⅱ scores) were important factors for cognitive reversal.

Objective:To investigate the therapeutic efficacy and disruptive effects of Meropenem（MEM）-loaded microbubbles（MBs）combined with ultrasound targeted microbubble destruction（UTMD）technology on Escherichia coli and its biofilm.Methods:MEM-MBs were prepared using the thin-film hydration method，and their characterization was assessed using a Zeta potential analyzer，with morphological observations conducted under an optical microscope. An in vitro biofilm model of periprosthetic joint infection（PJI）caused by Escherichia coli was constructed，and the morphology of the biofilm and the distribution of MEM-MBs in the bacterial biofilm were observed under a laser confocal microscope after staining the biofilm with SYTO59 staining and DIL staining for Microbubbles. The biofilm morphology and the distribution of MEM-MBs in bacterial biofilm were observed under laser confocal microscope. The biofilms were randomly divided into 5 groups using a random number table：control，Meropenem（MEM），MEM-MBs，UTMD，and MEM-MBs+UTMD，with 12 samples per group. After applying the respective interventions，scanning electron microscopy（SEM）and laser scanning confocal microscopy（LSCM）were employed to observe the effects on the morphology and structure of Escherichia coli and its biofilm. Crystal violet staining was utilized to determine and compare the biofilm density among groups using a microplate reader. LSCM was also used to observe the biofilm thickness，while both LSCM and spread plate counting were employed to assess bacterial viability differences across groups.Results:①MEM-MBs meeting the experimental requirements were successfully constructed.②A dense Escherichia coli biofilm visible under both the naked eye and LSCM was established，with a thickness of（10.61 ± 0.17）μm and a proportion of dead bacteria within the biofilm of（16.8 ± 0.8）%.③MEM-MBs were observed to penetrate into all layers of the biofilm using LSCM.④The results of crystal violet staining showed a decreasing trend in the biofilm density of the control group，the MEM group，the MEM-MBs group，the UTMD group，and the MEM-MBs+UTMD group. There was no significant difference between the MEM group and the MEM-MBs group（ P＞0.05），while there was a significant difference in biofilm density between the other groups，as revealed by pairwise comparison（all P＜0.05）.⑤UTMD technique and MEM-MBs+UTMD could significantly disrupt the biofilm of Escherichia coli. LSCM results showed that，compared to the control group，the thickness of the biofilm was reduced in all other groups，with only the UTMD group and the MEM-MBs+UTMD group showing an increase in porosity（both P＜0.05）. In comparison with the MEM group and the MEM-MBs group，the UTMD group showed an increase in porosity，while the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05）. Additionally，compared to the UTMD group，the MEM-MBs+UTMD group had a decrease in biofilm thickness and an increase in porosity（both P＜0.05），based on laser confocal microscopy results.⑥The results of the plate counting and LSCM showed that，compared with the control group，clump counts decreased，and the proportion of dead cells increased in the MEM group，the MEM-MBs group，and the MEM-MBs+UTMD group（all P＜0.05）. Compared with MEM group and MEM-MBs group，the clump counts of UTMD group increased，the proportion of dead cells decreased（all P＜0.05）；the clump counts of MEM-MBs+UTMD group decreased，and the proportion of dead cells increased（all P＜0.05）.Compared with UTMD group（all P＜0.05），the clump counts of MEM-MBs+UTMD group decreased，while the proportion of dead cells increased（all P＜0.05）.⑦The results of scanning electron microscopy revealed that the network structure of Escherichia coli was completely destroyed in the MEM-MBs+UTMD group. Conclusions:UTMD technology combined with MEM-MBs exerts a significant disruptive effect on the morphology and structure of Escherichia coli biofilm and significantly enhances bactericidal efficacy.

Objective:To propose a novel radiotherapy marking method-the"#"-character method,which aimed at improving the accuracy and repeatability of positioning during radiotherapy.Methods:A specially"cross-shaped"stamp was designed by this study,which consisted of a handheld square base with a"cross-shaped"protrusion.Using this stamp,the extreme positions of end-expiration and end-inspiration were marked respectively at the laser-guided regions on the directly above and bilateral sides of the patient's body,and each position was printed a"+"character.Finally,a"#-shaped"signal was formed,which represented the full range of respiratory motion of patients.The study included two parts:surface displacement caused by respiration was simulated through a three-dimensional(3D)motion platform,which was used to conduct a phantom experiment for anthropomorphic dummy,A randomized controlled study involving 40 patients,who were treated between January and June 2024 at the Department of Radiotherapy,Cancer Hospital,Chinese Academy of Medical Sciences,were conducted.The cohort included 20 patients with breast tumor(Positioning the outer contour by exposing the chest)and 20 patients with thoracic tumor(fixed position of using thermoplastic film).These patients were divided into two groups for comparison,which received respectively the"#-shaped"method and the conventional"+-shaped"method.The cone-beam computed tomography(CBCT)images before treatment were used to compare the influences of the two kinds of marking methods on the positioning errors of patients with breast tumor and patients with thoracic tumor.Then,the statistical analysis was used to assess precision and accuracy of positioning.Results:The result of phantom experiment indicated that the positioning error of the"#-shaped"method was significantly better than that of the"+-shaped"method under various parameters of respiratory movement.Under three kinds of different respiratory cycles(3,4,and 5 seconds)and amplitudes(8,12,and 15 mm),the positioning errors of the"#-shaped"method were respectively(0.15±0.04)cm,(0.19±0.05)cm and(0.35±0.14)cm,while the"+-shaped"method were respectively(0.42±0.16)cm,(0.64±0.28)cm and(0.88±0.37)cm,and the differences were statistically significant(t=8.347,3.416,2.901,P<0.05).The results of actual patients indicated the positioning error[(0.97±0.32)cm]of the"#-shaped"method was significantly lower than[(1.62±0.47)cm]of the"+-shaped"method for patients with breast tumor(Positioning the outer contour by exposing the chest),and the difference was significant(t=3.615,P<0.05).On the other hand,the positioning error[(0.69±0.24)cm]of the"#-shaped"method was significantly lower than[(0.97±0.39)cm]of the"+-shaped"method for patients with thoracic tumor(fixed position of using thermoplastic film),and the difference also was significant(t=1.934,P<0.05).Conclusion:Compared to the conventional"+-shaped"method,the"#-shaped"method appears higher accuracy and repeatability during the positioning process of radiotherapy,which especially is suitable to the treatment for breast tumor and thoracic tumor that need accurately control the influences of respiratory motion.