[Professor LIN Guo-hua's experience in the clinical application of "Dayingxiang"].

The paper introduces professor LIN Guo-hua's experience in treatment with acupuncture-moxibustion at "Dayingxiang". Based on the application of Neiyingxiang (internal LI 20), professor LIN defines the entire nasal cavity and its adjacent nasopharynx as "Dayingxiang", of which, "Neiyingxiang" and "Biyandian" (nasopharynx point) are commonly stimulated with acupuncture-moxibustion. "Dayingxiang" may regulate lung qi and promote the circulation of the marrow sea in treatment of the disorders of lung system and the marrow. Fire needling with twirling or burning-scallion technique is predominated in manipulation. "Neiyingxiang" is stimulated for the shallow-located disorders, while, "Biyandian" is for the deep-located ones. These two points are optioned alternatively or in combination to enhance the therapeutic effect.

Vaccination coverage determinants in low uptake areas of China: a qualitative study of provider perspectives in Sichuan, Guangdong, and Henan Provinces.

China's immunization programme is relatively strong, with latest WHO-UNICEF monitoring rates for 2019 showing national vaccination coverage over 90%. However, vaccination coverage is heterogeneous, varying across geographic regions, rural-urban communities, and sub-populations. We conducted a qualitative study from a critical realist perspective, analyzing semi-structured interviews with 26 vaccination providers in three provinces, selected to represent regional socioeconomic disparities across Eastern, Central, and Western China. We analyzed data thematically, using deductive and inductive coding. Providers reported vaccination coverage in their areas had increased significantly, but remained lower among migrant and left-behind children. Main coverage determinants were child-related (i.e. gender, number, health status), caregiver-related (i.e. socioeconomic status, role, education level, ethnicity), institution-related (i.e. vaccinator numbers, information system, appointment process), and system-related (i.e. vaccine supply, intersectoral cooperation, vaccine 'hesitancy'). Potentially effective measures to promote vaccination coverage included using routine maternal and child health-care visits for catch-up vaccination, providing additional health education, conducting follow-up family visits by village doctors, and requiring vaccination verification at school enrollment. This is the first qualitative study to examine potential determinants of low vaccination coverage in these areas of China. Findings can inform policies to strengthen the role of schools, develop the national immunization information system, and promote appointment apps. More consideration is needed to improve service quality and eliminating inequities, such as strengthening health education and service provision for migrant and left-behind children.

[Professor LIN Guo-hua's clinical experience in staging treatment for post-stroke dysphagia].

The paper summarizes professor LIN Guo-hua's clinical experience in staging treatment for post-stroke dysphagia. Professor LIN Guo-hua adheres to "essence and marrow deficiency and primary yang decline" as the pathogenesis and "conducting yin from yang " as the treating principle. By regulating the conception vessel and the governor vessel and focusing on yang meridians, in association with meridian differentiation and the location differentiation, professor LIN provides the staging treatment for post-stroke dysphagia. At the oral phase, yangming is dysfunction, manifested as facial paralysis and flaccid tongue. In treatment, reducing method is predominated at yangming meridian specially. At the pharyngeal phase, shaoyang is invaded by pathogens, manifested as pivoting dysfunction. The treatment focuses on communicating the exterior with the interior and promoting shaoyang meridian. At the esophageal phase, yangming meridian is deficiency and the turbid qi fails to descend, thus the reinforcing method is dominated to promote and tonify yangming. Additionally, the kinesiotherapy of acupuncture is assisted and the Lingnan fire needling therapy is used particularly. All of the summaries above provide the reference for the clinical treatment of post-stroke dysphagia.

[ZHANG Jia-wei's experience for treating press ulcer with fire-moxibustion].

To summarize ZHANG Jia-wei 's experience for treating press ulcer with fire-moxibustion. Through syndrome differentiation and examined factors, ZHANG Jia-wei believes that the disease is caused by qi deficiency and blood stasis, and advocates that the treatment should be weighed against deficiency and excess, and selection by stages. The cotton-moxibustion is used to diffusing and obstruction-removing qi and blood duingⅠstage of press ulcer. The Lingnan fire-needling is adopted for removing dampness, blood stasis and toxic substance to generate new muscles duringⅡand Ⅲ stage of press ulcer. Stage Ⅳof pressure ulcer and deep pressure ulcer should be treated with Taiyi moxa stick and aconite cake-separated moxibustion combined or alternately to expel toxin and grow muscles.

[Professor LIN Guo-hua's experience in treating intractable sudden deafness with acupuncture and moxibustion].

Professor LIN Guo-hua's experience and medical record in the treatment of intractable sudden deafness with acupuncture is introduced. Professor LIN believes that this disease is mainly caused by the blockage of shaoyang meridians, and should be treated with acupuncture therapy as soon as possible. According to the root cause and the pathogenesis of shaoyang blockage, the method of "soothing shaoyang, clearing the ear and opening the orifices" is adopted. In the treatment, Tinggong (SI 19) and acupoints in shaoyang meridians are selected as the main acupoints, and other acupoints based on meridian differentiation are selected as assisting acupoints. The manipulatingmethods of "fameng acupuncture" "blowing warm air into ear", and "Lingnan fire needling" are used synthetically. And qi and spirit are also regulated and front mu points are added if necessary to obtain satisfied effect of restore hearing.

miR-597-3p inhibits invasion and migration of thyroid carcinoma SW579 cells by targeting RAB23.

INTRODUCTION: Nowadays, it is indicated that miRNA was anomaly expressed in tumour. Previous studies have shown that miRNAs can regulate the proliferation, invasion, and migration of cancer cell-related processes. Meanwhile, current investigations show that RAB23 also plays an important role in cancer cell-related processes. But the potential mechanism remains unclear. MATERIAL AND METHODS: SW579 cells were selected and transfected with miR-597-3p mimics. Then the expression of miR-597-3p and RAB23 were measured by quantitative real-time polymerase chain reaction (PCR) and western blotting, respectively. Subsequently, the abilities of proliferation, invasion, and migration of SW579 cells were researched. For further study, the Luciferase reporter assay proved that miR-597-3p could target the expression of RAB23, and the proteins of invasion and migration were also measured to clear the mechanism. RESULTS: After being transfected with miR-597-3p mimics, the expression of miR-597-3p was remarkably increased and RAB23 was significantly decreased. The abilities of proliferation, invasion, and migration also decreased significantly. The miRTarase Database predicated and Luciferase reporter assay proved that RAB23 was the target gene of miR-597-3p. The expression of matrix metalloproteinase (MMP)-2, MMP-9, and N-cadherin was down-regulated, and the expression of E-cadherin was up-regulated. CONCLUSION: miR-597-3p could reduce the proliferation, invasion and migration abilities of SW579 cells, which may be related to the targeted inhibition of RAB23 expression and down-regulation of the expression levels of MMP-2, MMP-9 and N-cadherin proteins of SW579 cells.

Toll­like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi­1 expression.

Overproduction of pro­inflammatory cytokines in the aged, which is called inflammaging, leads to the deterioration of periodontitis. Toll­like receptor 4 (TLR4) plays a role in the regulation of cellular senescence, and its expression increases with age. However, there has been limited research into the molecular mechanisms underlying the onset of periodontal inflammaging, and the interplay between TLR4 and inflammaging. In the present study, wild­type and TLR4 gene knockout mice were used to investigate the activation of the TLR4 pathway in mouse periodontitis and the expression of the nucleotide­binding and oligomerization domain­like receptor 3 (NLRP3) inflammasome, an upstream immune checkpoint during the development of inflammaging. Activation of TLR4 in a mouse model of periodontitis enhanced the expression of a senescence­associated secretory phenotype (SASP), which boosted the inflammaging process. Conversely, TLR4 activation downregulated the expression of B cell­specific Moloney murine leukemia virus integration site 1 (Bmi­1) and promoted the priming of NLRP3 inflammasome, both of which are regulators of SASP. Treating gingival fibroblasts with Bmi­1 inhibitor PTC209, it was demonstrated that TLR4 activated the NLRP3 pathway and the inflammaging process by suppressing Bmi­1. In addition, there was a significant reduction in the expression of Bmi­1 expression in the gingiva of patients with periodontitis compared with healthy controls. In conclusion, the present study demonstrated that TLR4 acted by inhibiting Bmi­1 to enhance the NLRP3 pathway and SASP factors. This cascade of reactions may contribute to the senescence of the periodontium.

[Professor LIN Guo-hua's experience in the new clinical application of Yinjiao (GV 28)].

Yinjiao (GV 28) is generally used in treatment of lumbago and anorectal diseases. Professor LIN Guo-hua believes that Yinjiao (GV 28) is indicated in the disorders related to the sea of marrow and lower jiao by regulating the governor vessel and the conception vessel, promoting qi and blood circulation, tonifying the sea of marrow and adjusting the lower jiao. Based on professor Lin's clinical experience, "three Yinjiao" points are innovated, named Yinjiao (GV 28, upper Yinjiao), external Yinjiao and lower Yinjiao. Acupuncture therapy is generally optioned at Yinjiao (GV 28) and 5 needling principles are emphasized, i.e. accurate acupoint location, strong needling sensation, needling combined with body movement, alternative stimulation and allied stimulation. All of those mentioned above provide a new approach to the clinical treatment for the disorders related to the sea of marrow and lower jiao.

[Exploration of fire needling therapy on coronavirus disease 2019].

Combined with previous clinical experience in anti-epidemic and acupuncture, the prevention program of fire needling therapy for coronavirus disease 2019 (COVID-19) was drawn out. Fire needling therapy has the effects of clearing heat, removing dampness, replenishing for the deficiency, removing stasis and detoxifying, which is mainly aimed at preventing populations, light and common types cases, and cases in the recovery period. Acupoints of governor vessel, lung meridian, bladder meridian and stomach meridian are mainly used in this program. For the special groups, such as children, elderly and weak, and pregnant women, Shenzhu (GV 12), Danshu (BL 19), Geshu (BL 17), Zhigou (TE 6), etc. are added. It is hoped that fire needling therapy will be applied in the community and square cabin hospitals as an effective supplement to anti-epidemic of traditional Chinese medicine (TCM).

Long noncoding RNAs SET-binding factor 2-antisense RNA1 promotes cell growth through targeting miR-431-5p/CDK14 axis in human papillary thyroid cancer.

Papillary thyroid cancer (PTC) is a frequent thyroid malignancy. With the significant regulatory role in tumor progression, more attention has been employed to investigate mechanism of long noncoding RNAs (lncRNAs) in progression of PTC. We prospectively explored the mechanism whereby lncRNA SET-binding factor 2-antisense RNA1 (SBF2-AS1) is implicated in pathogenesis of PTC. First, differentially expressed SBF2-AS1 between PTC and normal adjacent thyroid tissues was determined, and result indicated a higher SBF2-AS1 expression in PTC tissues than adjacent normal tissues. Moreover, highly SBF2-AS1 expression predicted a poor prognosis in PTC patients. Second, SBF2-AS1 overexpression promoted cell viability and cycle of PTC, while inhibited cell apoptosis. However, SBF2-AS1 downregulation reduced viability and cycle, while promoted cell apoptosis. Moreover, SBF2-AS1 could bind with miR-431-5p and showed negative correlation with miR-431-5p in PTC patients. Furthermore, miR-431-5p bind with cyclin-dependent kinase (CDK) 14 and showed negative correlation with CDK14 in PTC patients. Finally, overexpression of CDK14 counteracted with the inhibitory role of SBF2-AS1 downregulation on cell viability, cycle, and apoptosis of PTC. In conclusion, SBF2-AS1 exhibited oncogenic property in PTC, and knockdown of SBF2-AS1 could be a therapeutic strategy for PTC.

Poloxamer modified florfenicol instant microparticles for improved oral bioavailability.

Surfactants can improve the hydrophobicity of poorly water-soluble drugs and increase the stability of microparticles by reducing surface tension. This study describes that surfactant-engineered florfenicol instant microparticles (FIMs) increase bioavailability through a micellar solubilization mechanism. The FIMs were prepared by a modified emulsification method, and the optimal prescription was obtained by a combination of single factor investigation and response surface methodology. The microparticles prepared in this study reduce the polymer materials while increasing the drug content. FIM has a smaller particle size and modification of poloxamer, resulting in better solubility and higher bioavailability. The in vitro solubility of FIM is 1.43 times higher than that of the bulk drug, and the dissolution equilibrium can be achieved in 10 minutes. Compared with florfenicol, FIM showed a decrease in Tmax in the plasma concentration curve, with a peak concentration of 1.43 times and an area of 1.41 times. Considering the advantages of in vitro/in vivo performance and ease of preparation, FIMs may have great application prospects in pharmacy research.

[Professor LIN Guo-hua's experience in treatment of progressive muscular dystrophy with acupuncture].

Professor LIN Guo-hua's experience is introduced in treatment of progressive muscular dystrophy with acupuncture. It is believed that the pathogenesis of this disease is related to spleen and kidney deficiency, qi and blood insufficiency and malnutrition of tendon and muscle. The treatment is determined in terms of the pathogenesis and focuses on the regulation of spleen and kidney functions. The thinking of treatment is summarized as exerting the strong stimulation of acupuncture specially at the acupoints on the head, supplementing the sea of marrow, adjusting simultaneously the three yang meridians, rather than treating particularly yangming meridian and regulating qi in priority and considering the lung function for wei (flaccid) syndrome. Moreover, in clinical treatment, the acupoint thread-embedding therapy is commonly combined to ensure the significant therapeutic effect.

[Professor LIN Guo-hua's clinical experience of acupuncture for oculomotor nerve paralysis].

Professor LIN Guo-hua's clinical experience of acupuncture for oculomotor nerve palsy was summarized and one typical case was introduced. Professor LIN skillfully applied traditional acupuncture theory and classical acupuncture method, and proposed a diagnosis and treatment system combining meridian syndrome differentiation and specific acupuncture techniques. In addition, Professor LIN combined the yuan-primary and luo-connecting acupoints combination method, theory of "removing the stagnation of blood and qi " and theory of root-stem and origin-end, etc. into the treatment of oculomotor nerve palsy, and achieved good results.

Protective Effects of Salidroside against Carbon Tetrachloride (CCl4)-Induced Liver Injury by Initiating Mitochondria to Resist Oxidative Stress in Mice.

The antioxidant effect of salidroside has been proven, but its role in liver injury is poorly understood. In this study, we aimed to evaluate the protective effects and mechanism of salidroside on liver injury induced by carbon tetrachloride (CCl4) in vivo. Mice were pretreated with salidroside (60 mg/kg, intraperitoneally injected, i.p.) once per day for 14 consecutive days and then administered with CCl4 (15.95 g/kg, i.p.) for 24 h to produce a liver injury model. Salidroside attenuated hepatic transaminase elevation in serum and ameliorated liver steatosis and necrosis, thereby suggesting its protective effect on the liver. Salidroside antagonized CCl4-induced toxicity by equilibrating antioxidation system, thereby inhibiting reactive oxygen species accumulation, and restoring mitochondrial structure and function. Salidroside exerts antioxidant and liver-protective effects by selectively inhibiting the activation of genes, including growth arrest and DNA -damage-inducible 45 α (Gadd45a), mitogen-activated protein kinase 7 (Mapk7), and related RAS viral oncogene homolog 2 (Rras2), which induce oxidative stress in the mitogen-activated protein kinase pathway. These results revealed that salidroside can protect the liver from CCl4-induced injury by resisting oxidative stress and protecting mitochondrial function.

P16INK4a played a critical role in exacerbating acute tubular necrosis in acute kidney injury.

Acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality, which is mostly caused by acute tubular necrosis (ATN). AKI is associated with many factors, including cell senescence, inflammatory infiltration, apoptosis and excessive accumulation of reactive oxygen species (ROS). P16INK4a (hereafter termed p16) inhibits cell cycle, and the absence of p16 can significantly slow the progression of cell senescence. We found that the expression of p16 was significantly increased after ATN. To determine whether p16 could exacerbate ATN degree and whether p16 deletion had protective effects against the ATN and renal dysfunction in AKI progression, glycerol-rhabdomyolysis-induced ATN was performed in eight-week-old p16 knockout and wild-type (WT) littermates. Their ATN phenotypes were analyzed; the levels of serum creatinine and serum urea nitrogen were detected; inflammation, cell apoptosis, ROS level and ROS signaling pathway molecules were examined using histopathological and molecular techniques. We found that compared to WT mice, p16 deletion has protective effects against the ATN phenotype and renal dysfunction in AKI progression through ameliorating inflammatory infiltration and proinflammatory factor expression by inhibiting NF-κB proinflammatory pathway, decreasing cell apoptosis by balancing the expressions between pro-apoptotic and anti-apoptotic molecules, and reducing ROS levels and downregulating ROS signaling pathway molecules including AIF, PGAM5 and KEAP1. Thus, p16 deletion or inhibition and p16 positive cell clearance would be a novel strategy for preventing ATN in AKI progression.

Effect of tetrahedral DNA nanostructures on osteogenic differentiation of mesenchymal stem cells via activation of the Wnt/ß-catenin signaling pathway.

Adipose-derived stem cells (ADSCs) are considered to be ideal stem cell sources for bone regeneration owing to their ability to differentiate into osteo-like cells. Therefore, they have attracted increasing attention in recent years. Tetrahedral DNA nanostructures (TDNs), a new type of DNA-based biomaterials, have shown great potential for biomedical applications. In the present work, we aimed to investigate the role played by TDNs in osteogenic differentiation and proliferation of ADSCs and tried to explore if the canonical Wnt signal pathway could be the vital biological mechanism driving these cellular responses. Upon exposure to TDNs, ADSCs proliferation and osteogenic differentiation were significantly enhanced, accompanied by the up-regulation of genes correlated with the Wnt/ß-catenin pathway. In conclusion, our results indicate that TDNs are crucial regulators of the increase in osteogenic potential and ADSCs proliferation, and this noteworthy discovery could provide a promising novel approach toward ADSCs-based bone defect regeneration.