Pulmonary sarcoidosis is an immune system disease with an unclear etiology. Guided by the yang-reinforcing method， it is believed that the fundamental pathogenesis of pulmonary sarcoidosis lies in the disharmony between water and fire and the reckless movement of the ministerial fire. The failure of the spleen and stomach to maintain warmth， leading to the production of phlegm and blood stasis， is an important pathogenesis. The invasion of external pathogenic toxins， deeply penetrating into the interior， is considered a triggering factor for the disease. The treatment focuses on supplementing the yang， consolidating the kidney， drawing fire back to its source， warming the yang， benefiting the kidney， and nourishing the spleen to generate metal. It also emphasizes unblocking the yang， transforming turbidity， and eliminating phlegm and blood stasis.

Refractory chronic cough belongs to the category of "refractory cough" in traditional Chinese medicine， and it is believed that the root cause of intractable chronic cough is wind lodging in the spleen collaterals， with poor spleen yang and deficient kidney essence as the pathologic basis of the disease， which is present throughout the disease. The method advocated is to search the spleen collaterals and eliminate latent wind， warm the spleen yang and smooth the middle jiao， cultivate the kidney essence and consolidate the root， prescribed with modified Fuzi Lizhong Decoction （附子理中汤） plus Erxian Decoction （二仙汤） as the basis. The Fuzi Lizhong Decoction can warm yang and fortify the middle， and smooth the middle jiao， and the Erxian Decoction can cultivate the kidney essence and consolidate the innate. The two prescriptions could combine with Suye （Perilla frutescens）， Jingjie （Dysphania ambrosioides）， Fangfeng （Carum carvi） and other medicinals of cleaning characteristic， or combine with Gouteng （Uncaria rhynchophylla）， Chuanshanlong （Dioscorea nipponica）， Dilong （Kummerowia striata） and other medicinals of worm or cane category， to find the wind and expel pathogen， smooth spleen collaterals.

This article is based on ZHANG Jingyue's theory of yin-yang holism to explore the etiology， pathogenesis， and treatment of acute exacerbation of rheumatoid arthritis-associated interstitial lung disease （RA-ILD）. It is believed that the foundation of acute exacerbation of RA-ILD lies in real yin insufficiency and yin fail to control yang； external pathogen attacking is a common cause of acute exacerbation of RA-ILD. For treatment， it is important to first suppress ministerial fire by prescribing modified Yinhuo Decoction （引火汤）； if ministerial fire submerged， focus should be on nourishing both yin and yang； if real yin deficiency is the main issue， modified Zuogui Pill （左归丸） should be used； if real yang deficiency is prominent as well， modified Yougui Pill （右归丸） can be chosen. When yin and yang balanced， the disease could be solved.

It is believed that the fundamental pathogenesis of the connective tissue diseases-associated interstitial lung disease （CTD-ILD） is kidney essence deficiency， with lung collateral obstruction throughout the disease， and environmental toxin pathogen is the important causative factors for the development of CTD-ILD. This article proposed to restore origin and alleviate bi （痹） for CTD-ILD， for which restoring origin means tonifying the lungs， spleen and kidneys to bank up the roots and consolidate the original qi， with modified Erxian Decoction （二仙汤） plus Liu Junzi Decoction （六君子汤）； alleviating bi means expelling wind and dredging collaterals， and eliminating the mass to restore the smoothness of the lung collaterals， with paired medicines of Chuanshanlong （Dioscorea nipponica）-Dilong （Kalanchoe pinnata）， Vinegar-processed Sanleng （Sparganium stoloniferum）-Vinegar-processed Ezhu （Curcuma zedoaria）， and stem-type medicines， and emphasized on removing the environmental toxin pathogens to facilitate the recovery of healthy qi.

Objective : To investigate the effects of D ⁃allose on the restoration of neurological function , Galectin⁃3 (Gal⁃3) , adenosine monophosphate⁃activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) and the expression of some inflammatory factors in ischemia⁃reperfusion injury ( CIRI) mice . Methods : A total of 50 male mice were randomly divided into control group (Con group) , sham group (Sham group) , cerebral ischemia⁃reperfusion injury group (MCAO group) , cerebral ischemia⁃reperfusion injury + D ⁃alolose group (MCAO + D ⁃allose group) and cerebral ischemia⁃reperfusion injury + modified citrus pectin group (MCAO + MCP group) . The middle cerebral artery occlusion/reperfusion (MCAO/R) model (reperfusion after 2 hours of MCA ischemia) was established by thread embolism . After successful modeling , the neurological function of mice was evaluated Longa score and rotated rod walking . TTC staining was used to observe the volume of cerebral infarction foci . The expression levels of Gal⁃3 and autophagy⁃related molecules were detected by Western blot and RT⁃PCR . Immunofluorescence was applied to detect the distribution of Gal⁃3 in brain tissue , and TNF⁃α , IL⁃8 secretion was detected with ELISA KIT . Results : Compared with Con group and Sham group , the MCAO model represented significant increase in the Longa neurofunction score (P < 0. 01) , cerebral infarction volume ( P < 0. 01) , Gal⁃3 expression and manifasted enhanced autophagy (P < 0. 01) . After treatment with D ⁃allose , it could significantly improve neurological dysfunction , reduce cerebral infarction volume (P < 0. 01) , reduce the expression of Gal⁃3 ( P < 0. 01) , inhibit AMPK phosphorylation , promote mTOR phosphorylation , and inhibit autophagy (P < 0. 01) . The use of the Gal⁃3 inhibitor MCP alone could also achieve the effect of inhibiting autophagy . Conclusion D ⁃allose can effectively promote the recovery of neurological function and reduce the volume of infarct foci in CIRI mice . The mechanism may involve inhibiting excessive cell autophagy by downregulating the expression of Gal⁃3 , and reducing the release of inflammatory factors such as TNF⁃α and IL⁃8 , thereby exerting neuroprotective effects .

Bronchiectasis is a refractory chronic airway disease characterized by chronic cough and phlegm production. Airway mucus hypersecretion is one of the important causative factors for acute exacerbation of bronchiectasis. Thus， reducing airway mucus secretion during the stable phase of bronchiectasis is the key to the treatment. Phlegm-dispelling therapy is commonly used in modern medicine， which， however， fails to radically reduce mucus secretion. At the moment， it is difficult and urgent to find an intervention that can improve the quality of life of patients and reduce the recurrence of disease during the stable phase of bronchiectasis. Chinese medicine shows remarkable efficacy in reducing airway mucus secretion. Nonetheless， there is a lack of research on the airway mucus hypersecretion of bronchiectasis， and no registered research outcome is available. Traditional Chinese medicine boasts a lot of experience in the treatment of phlegm. It combines clearing and tonifying methods and identifies Yin and Yang and internal organs， thus being advantageous in the treatment of airway mucus hypersecretion of bronchiectasis. Therefore， it is an important topic to improve the effectiveness of Chinese medicine on airway mucus hypersecretion of bronchiectasis by focusing on the "generation"， "transformation" and "excretion" of phlegm.

Objective: To understand the characteristics of injury deaths of children and adolescents aged 0 to 19 years in Kunming during 2010-2019,and to provide injury prevention and control basis. Methods: Injury mortality data in 2010-2019 were from Kunming population based mortality surveillance system. The characteristics of injury death of children and adolescents were analyzed by descriptive statistical analysis, including mortality rate, composition ratio, the annual percent change,etc. Results: Child and adolescent injury mortality was 23.18/10 5,decreasing by year(t=7.13,P<0.05). Male mortality(31.59/10 5) was higher than female(14.27/10 5)(χ2=376.24,P<0.05),the APC of male was -8.82% and -7.48% in female.The injury mortality of male was higher than that of female at all age group. The injury mortality rate of rural children and adolescents(28.65/10 5) was higher than that of urban children(12.37/10 5)(χ2=297.30,P<0.05),the APC was -8.53% in urban areas and -7.78% in rural areas.The top five causes of injury death of children and adolescents were traffic accident drowning, accidental fall, suicide and accidental mechanical suffocation, accounting for 80.88% of the total injury deaths of children and adolescents.In urban and rural areas,injury death by traffic accident, drowning and rural unintentional falls decreased significantly(t urban=3.17,3.20,t rural=5.66,3.12,4.42,P<0.05). The leading cause of death varied by different age groups. Conclusion The injury mortality rate of children and adolescents in Kunming city is on the decline. Rural children and adolescents, as vulnerable population to injury death, should receive protective strategies according to their specific characteristics of injuries and deaths in different age groups.

Wnt signaling has emerged as a major regulator of tissue development by governing the self-renewal and maintenance of stem cells in most tissue types. As a key upstream regulator of the Wnt pathway, the transmembrane E3 ligase ZNRF3 has recently been established to play a role in negative regulation of Wnt signaling by targeting Frizzled (FZD) receptor for ubiquitination and degradation. However, the upstream regulation of ZNRF3, in particular the turnover of ZNRF3, is still unclear. Here we report that ZNRF3 is accumulated in the presence of proteasome inhibitor treatment independent of its E3-ubiquitin ligase activity. Furthermore, the Cullin 1-specific SCF complex containing β-TRCP has been identified to directly interact with and ubiquitinate ZNRF3 thereby regulating its protein stability. Similar with the degradation of β-catenin by β-TRCP, ZNRF3 is ubiquitinated by β-TRCP in both CKI-phosphorylation- and degron-dependent manners. Thus, our findings not only identify a novel substrate for β-TRCP oncogenic regulation, but also highlight the dual regulation of Wnt signaling by β-TRCP in a context-dependent manner where β-TRCP negatively regulates Wnt signaling by targeting β-catenin, and positively regulates Wnt signaling by targeting ZNRF3.
Cells, Cultured ; Humans ; Proteolysis ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitination ; beta-Transducin Repeat-Containing Proteins ; metabolism

OBJECTIVE:To compare the clinical efficacy of raloxifene and clomiphene in the treatment of polycystic ovary syndrome(PCOS)complicated with infertility. METHODS:In retrospective study,clinical information of 137 PCOS patients with infertility in our hospital during Jun. 2012-Feb. 2015 were selected and divided into raloxifene group(70 cases)and clomiphene group(67 cases)according to therapy plan. Raloxifene group received Raloxifene tablet 120 mg at the fifth day of menstrual cy-cle,qd,for consecutive 5 d. Clomiphene group received Clomiphene citrate capsule 100 mg at the fifth day of menstrual cycle, qd,for consecutive 5 d. Both groups received B-ultrasound to detect the follicular diameter and endometrial development at the twelfth day of menstrual cycle. When endometrial thickness was ≥7 mm and the diameter of one follicle was ≥18 mm at least,all patients received abdominal subcutaneous injection of Triptorelin acetate injection 0.1 mg to induce ovulation;after 48 h,ovulation was confirmed by B ultrasound. The patients with insufficient luteal function should take dydrogesterone 10 mg as appropriate,q12 h,till 15 d after ovulation. The endometrial thickness,the number of follicles with diameter≥18 mm and follicular maturation time were compared between 2 groups on the day of injection. The sex hormone levels before treatment and on the day of injection,as well as ovulation,outcome indexes and the occurrence of ADR in 2 groups were compared. RESULTS:The endometrial thickness of raloxifene group was greater than that of clomiphene group;the number of follicles with diameter ≥18 mm was more than clo-miphene group;the follicular maturation time was shorter than clomiphene group,with statistical significance(P<0.05). Before treatment,there was no statistical significance in serum levels of P,E2,FSH and LH between 2 groups(P>0.05). Compared to before treatment,there was no statistical significance in serum levels of P,E2,FSH or LH in 2 groups on the day of injection(P>0.05). Serum levels of LH in 2 groups were decreased significantly,and serum level of LH in raloxifene group was significantly lower than in clomiphene group,with statistical significance(P<0.05). The ovulation rate of raloxifene group was significantly higher than clomiphene group,with statistical significance(P<0.05);while the pregnancy rate,abortion rate,continuous pregnan-cy rate of 2 groups had no statistical significance(P>0.05). There was no statistical significance in the total incidence of ADR (5.71% vs. 8.96%)between 2 groups(P>0.05). CONCLUSIONS:Raloxifene has better ovulation induction effect than clomi-phene,and it can improve the sex hormone levels of PCOS patients with infertility,with few ADR,and similarity in long-term clinical effect with clomiphene.