Osteoporosis （OP） is a systemic metabolic disease with a strong correlation with age. The prevalence of osteoporosis is rising annually as a consequence of the growing issue of population ageing. The current treatments for OP have numerous shortcomings. In contrast， traditional Chinese medicine has a long history and a rich species diversity. Furthermore， recent years have seen an increase in the number of studies examining the anti-OP properties of traditional Chinese medicine. This may provide a safe and effective alternative strategy for the treatment of OP. The zebrafish， due to its favourable optical transparency and high homology with human genes， has been extensively employed as an animal research model in the investigation of human skeletal-related disease mechanisms and drug screening. This paper presents a review of anti-osteoporosis studies of traditional Chinese medicine using zebrafish as a model for osteoporosis. It also provides a summary of the experimental evaluation methods involved in such studies， an analysis of the current status of traditional Chinese medicine in the treatment of osteoporosis using zebrafish as a model， and a summary of the mechanism of action and the signalling pathways involved in traditional Chinese medicine in the anti-osteoporosis treatment of zebrafish. The current research status of Chinese medicine in the treatment of OP was analysed， as well as the mechanism of action of Chinese medicine against OP and the signalling pathways involved. Furthermore， the advantages and disadvantages of various zebrafish modelling methods of OP were compared with those of traditional animal models. The objective of this study is to provide a reference for the evaluation method of the zebrafish model in the study of bone-related diseases， as well as for the study of the mechanism of action of traditional Chinese medicine against OP and for the reference of the research and development of new drugs.

BACKGROUND:Upregulation of hedgehog protein signaling can increase the expression of osteoarthritis markers,Runx2,a disintegrin and metalloproteinase with thrombospondin motifs,collagen type X alpha 1,and matrix metalloproteinase 13,while inhibition of hedgehog proteins attenuates the severity of osteoarthritis.It is speculated that osteoarthritic chondrocytes can influence bone formation by affecting osteoblasts through the Indian hedgehog protein(IHH)signaling pathway. OBJECTIVE:To investigate the effect of human osteoarthritic chondrocytes on subchondral osteoblasts. METHODS:Tibial plateau specimens from patients with osteoarthritis were collected.Chondrocytes were extracted using enzymatic digestion,and osteoblasts were extracted using enzymatic pre-digestion + bone block method.Chondrocytes were identified by toluidine blue staining and immunofluorescence and osteoblasts were identified by alkaline phosphatase staining and immunofluorescence.Chondrocytes were cultured in sodium alginate beads to maintain chondrocyte phenotype and co-cultured with osteoblasts.The co-culture system was added with IHH signaling pathway inhibitor(cyclopamine,10 nmol/L)and activator(purmorphamine,10 nmol/L)separately.After 48 hours of co-culture,osteoblasts from each group were collected,mRNA expressions of Gli1,osteoprotegerin,Runx2,parathyroid hormone-related peptide,alkaline phosphatase,receptor activator of nuclear factor-kB ligand(RANKL)and osteocalcin were detected by qRT-PCR,and protein expressions of GLi1,oseoprotegerin and RANKL in osteoblasts were detected by western blot. RESULTS AND CONCLUSION:The mRNA expression levels of GLi1,osteoprotegerin and RUNX2 in osteoblasts were significantly increased,while the mRNA expression levels of parathyroid hormone-related peptide were decreased(P＜0.05)when co-cultured with human osteoarthritic chondrocytes.The mRNA and protein levels of Gli1 were significantly decreased after the addition of IHH signaling pathway inhibitor(cyclopamine)(P＜0.05),and the mRNA and protein levels of Gli1 were significantly increased after the addition of IHH signaling pathway activator(purmorphamine)(P＜0.05).Osteoprotegerin showed the same trend as Gli1 in the experiment.The osteoprotegerin/RANKL ratio followed the same trend as osteoprotegerin.To conclude,human osteoarthritic chondrocytes can promote the expression of Gli1,osteoprotegerin,Runx2 and other proteins in osteoblasts.The upregulation of osteoprotegerin is related to the IHH signaling pathway.Osteoarthritic chondrocytes can up-regulate the expression of osteoprotegerin in osteoblasts through the IHH signaling pathway and thus up-regulate the osteoprotegerin/RANKL ratio,which will contribute to bone formation in subchondral bone.

ObjectiveTo clarify the relationship between intestinal flora and intestinal motility in rats with slow transit constipation （STC） and qi stagnation syndrome by conducting a pseudo-sterile experiment and fecal microbiota transplantation （FMT） technology. MethodsTwenty-four Wistar rats were randomly divided into normal group （n=6）， STC with qi stagnation pattern group （n=6） and pseudo-sterile group （n=12）. In the STC group with qi stagnation pattern， 3 mg/kg of loperamide suspension by intragastric administration combined with tail clamping stimulation were performed to establish the rat model of STC with qi stagnation pattern. After successful modeling， fresh feces from the rats in the STC with qi stagnation pattern group and the normal group were collected to prepare 100 mg/ml of fecal bacterial suspension. In the pseudo-sterile group， the antibiotic cocktail method was used （a mixed antibiotic suspension containing bacitracin， streptomycin sulfate， and neomycin sulfate at 20 mg/ml each was administered intragastrically） to establish pseudo-sterile rats model. After successful modeling， the rats were randomly divided into normal fecal bacterial liquid group and STC with qi stagnation pattern fecal bacterial liquid group， with six rats in each group， and then were given 10 ml/kg of the prepared corresponding rat fecal bacterial suspension by gavage. Rats in STC with qi stagnation pattern group were given an equal volume of sterile water by gavage. All groups were administered once a day for 7 consecutive days. The small intestinal propulsion rate of the STC with qi stagnation pattern group， the normal fecal bacterial liquid group， and STC with qi stagnation pattern fecal bacterial liquid group were compared. ELISA method was used to detect serum 5-hydroxytryptamine （5-HT） levels. Immunohistochemistry was used to detect the positive expression levels of 5-hydroxytryptamine 3 receptor （5-HT3R） and 5-hydroxytryptamine 4 receptor （5-HT4R） in colon tissue. Western blot method was used to detect the protein expression levels of tryptophan hydroxylase 1 （TPH1）， tryptophan hydroxylase 2 （TPH2）， serotonin transporter （SERT）， and monoamine oxidase A （MAO-A） in colon tissue. ResultsCompared to those in the normal fecal bacterial liquid group， the small intestinal propulsion rate， serum 5-HT level， positive expression of 5-HT3R and 5-HT4R in colon tissue， and protein expression of TPH1， TPH2， SERT and MAO-A significantly decreased in the STC with qi stagnation pattern group and STC with qi stagnation pattern fecal bacterial liquid group （P＜0.05）. There was no statistically significant difference in the indicators between the STC with qi stagnation pattern group and STC with qi stagnation pattern fecal bacterial liquid group （P＞0.05）. ConclusionThe intestinal flora in STC rats with qi stagnation pattern can lead to a slowdown in intestinal transmission function， whose mechanism may be related to intestinal motility disorders affected by the synthesis， transport， metabolism and other pathways of 5-HT.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

Objective To investigate the effects of calcitriol intervention on PI3K/AKT signaling pathway and wound healing in rats with diabetic foot ulcer(DFU).Methods Thirty-two male SD rats were divided into normal control(Con)group,DFU group,calcitriol low dose(L)group and calcitriol high dose(H)group.A circular wound of 5 mm in diameter and deep to the fascia was made on the dorsum of the left foot of rats in each group.HE staining was used to evaluate the histopathological changes of the wounds.Immunohistochemical method was selected to compare the distribution of CD34-positive cells and the expression of p-PI3K and p-AKT in traumatic tissues of each group.ELISA was adopted in the detection of serum IL-6,IFN-γ,TNF-α and IL-7.RT-PCR was used to detect the mRNA expression of PI3K and AKT in each group,and western blot was used to detect the protein expression of PI3K,p-PI3K,AKT,p-AKT and VEGF.Results Compared with Con group,the expressions of IL-6,IFN-γ,TNF-α,IL-7,CD34,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K,p-AKT/AKT increased,while PI3K protein expression decreased in DFU,L and H groups(P<0.05),VEGF and AKT protein expression decreased in DFV and L groups(P<0.05).Compared with DFU group,the expressions of VEGF,AKT and PI3K protein increased(P<0.05),while the expressions of p-PI3K/PI3K,p-AKT/AKT decreased in L and H groups(P<0.05),IL-6 decreased in L group(P<0.05),and CD34 expression increased in H group(P<0.05),while IL-6,IFN-γ,TNF-α and IL-7,PI3K mRNA,AKT mRNA,p-AKT protein and p-PI3K protein expression decreased(P<0.05).Compared with L group,the expressions of CD34,VEGF,AKT and PI3K protein increased(P<0.05),while IL-6,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K and p-AKT/AKT decreased in H group(P<0.05).Conclusions Calcitriol intervention may reduce the activity of the PI3K/AKT signaling pathway,inhibit inflammation,promote neovascularization,and facilitate wound healing in rats with DFU.

Objective The risk evaluation indicators for the occurrence of diaphragm dysfunction in ICU patients was constructed to provide a reference for the establishment of the disease risk evaluation tools for diaphragm dysfunction.Methods The literature related to diaphragm dysfunction from CNKI,Wanfang Data,PubMed,Embase and Web of Science from the establishment of databases to November 11 th,2022 was systematically searched.After the first draft was determined through the literature review method,the first draft of the indicators was revised by brainstorming,with the opinions of 10 medical and nursing experts from May to June 2023.From June to July 2023,the content and weight of risk evaluation indicators of diaphragmatic dysfunction in ICU patients were determined through expert letter inquiry and hierarchical analysis.Results 35 experts completed the first round of letter inquiry,and 34 experts completed the second round of letter inquiry.The recovery rates of the valid questionnaires in the 2 rounds of expert correspondence were 92.1％and 97.1％,respectively,and the expert authority coefficients were 0.884 and 0.904,respectively,and the Kendall harmony coefficients of all indicators were 0.356～0.570 and 0.369～0.604,respectively(all P＜0.001).The final constructed risk evaluation indicators of diaphragm dysfunction in ICU patients includes 7 first-level indicators,34 secondary indicators and 34 tertiary indicators.Conclusion The risk evaluation index of diaphragm dysfunction in ICU patients constructed in this study is comprehensive,specific,scientific and applicable,which can guide medical staff to conduct early risk evaluation of diaphragm function in ICU patients,and provide references for the establishment of disease risk assessment tools for diaphragm function.

OBJECTIVE To analyze the status quo of performance appraisal of pharmacy intravenous admixture services （PIVAS） in China based on literature analysis， and provide reference for the implementation of performance management of PIVAS in China. METHODS Retrieved from domestic and foreign databases such as CNKI， VIP， Wanfang， PubMed， Embase， the Cochrane Library and CBM， the literature on the status quo evaluation of performance appraisal of PIVAS in China was included from the inception to Sept. 2022. The descriptive analysis was carried out on performance appraisal measures， performance appraisal indicators， performance appraisal achievement， etc. RESULTS Twelve pieces of literature were included， involving 8 before-and-after controlled studies and 4 experience sharing. The performance appraisal subjects of 10 pieces of literature were all staff and those of 2 pieces of literature were nurses. The measures of PIVAS performance appraisal were roughly the same， mainly involving contents and indicators of workload， work quality （including errors）， clinical service satisfaction， labor discipline， department contribution， personal comprehensive evaluation， and so on， but the main accounting proportion was different. Performance appraisal indicators mainly included the rate of medical order review， dispensing rate， check rate， delivery rate， finished product review rate， etc. The performance appraisal achievement mainly included the improvement of work efficiency， the improvement of work quality， the reduction of error rate， and the improvement of clinical satisfaction and employee satisfaction. CONCLUSIONS By building performance appraisal system and adopting corresponding performance management measures of PIVAS， it can improve the work efficiency and quality， reduce the error rate， ensure the safety of patients’ medication， and promote the standardized management of PIVAS in China.

Endoplasmic reticulum (ER) stress, as an emerging hallmark feature of cancer, has a considerable impact on cell proliferation, metastasis, invasion, and chemotherapy resistance. Ovarian cancer (OvCa) is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis. Studies have explored the influence of ER stress on OvCa in recent years, while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored. Here, we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts for the screening of prognosis-related genes. The least absolute shrinkage and selection operator (LASSO) regression was applied to establish an ER stress-related risk signature based on the TCGA cohort. A seven-gene signature revealed a favorable predictive efficacy for the TCGA, International Cancer Genome Consortium (ICGC), and another GEO cohort (P<0.001, P<0.001, and P=0.04, respectively). Moreover, functional annotation indicated that this signature was enriched in cellular response and senescence, cytokines interaction, as well as multiple immune-associated terms. The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group. In conclusion, ER stress-related genes are vital factors predicting the prognosis of OvCa, and possess great application potential in the clinic.
Humans ; Female ; Ovarian Neoplasms/genetics* ; Cell Proliferation ; Cytokines ; Endoplasmic Reticulum Stress/genetics*

Autophagy， a mechanism of cell self-protection and self-renewal， is associated with the occurrence and development of lung cancer. Favorable autophagy can slow down the progression of lung cancer， while unfavorable autophagy can promote the progression. Therefore， regulating the level of autophagy is of great significance in the treatment of lung cancer. Healthy Qi deficiency and pathogenic Qi stagnation is an extension of the theory of deficiency and Qi stagnation proposed by the Academician WANG Yongyan. It refers to the pathological process that the abnormal body fluid metabolism caused by Qi deficiency of lung， spleen， and kidney results in phlegm and blood stasis. Lung cancer has the root cause of Qi deficiency of lung， spleen， and kidney and the syndrome of phlegm and blood stasis. The autophagy in lung cancer is interconnected with healthy Qi deficiency and pathogenic Qi stagnation. The Qi deficiency of lung， spleen， and kidney is the key factor for the weakening of favorable autophagy in lung cancer， which inhibits the apoptosis of tumor cells and leads to the accumulation of harmful substances. Phlegm and blood stasis is a direct factor enhancing the unfavorable autophagy in lung cancer， which promotes the autophagic death of normal cells， weakens the immunosuppressive effect of immune cells on tumor cells， and leads to the proliferation and migration of tumor cells. The combination of healthy Qi deficiency and pathogenic Qi stagnation results in the development of autophagy in an unfavorable direction and finally leads to the continuous progression of lung cancer. Therefore， the traditional Chinese medicine （TCM） treatment of lung cancer should follow the principle of reinforcing healthy Qi and expelling pathogenic Qi， removing phlegm and resolving stasis， so as to enhance favorable autophagy while inhibiting unfavorable autophagy. Such therapy can inhibit the proliferation and migration of tumor cells and promote the remission of lung cancer. According to the existing literature， Chinese medicine monomers are mainly used to treat lung cancer by regulating autophagy. The Chinese medicine intervention of autophagy in lung cancer mainly aims to promote the activation of autophagy. This may be because the favorable autophagy weakening caused by the Qi deficiency of lung， spleen， and kidney is the fundamental reason for the development of lung cancer.

Bipolar disorder （BD） is a serious chronic emotional disorder with a high suicide rate and a common psychiatric disease. Traditional Chinese medicine （TCM） treatment based on syndrome differentiation of BD has unique advantages and good safety， which is expected to become a breakthrough in the treatment. Based on Expert Consensus on TCM Syndrome Differentiation Criteria for Bipolar Disorder by Professor Yin Dongqing and Professor Jia Hongxiao， this study collated the treatment protocols of BD with various syndrome types according to Meta-analysis of the existing literature in the database and evaluated the evidence level according to the evidence evaluation standard issued by the US Agency for Healthcare Research and Quality （AHRQ）. （1） Depression attack. ① Liver depression and spleen deficiency syndrome： Xiaoyaosan pills or Shugan Jieyu capsules， ② Phlegm dampness and spleen stagnation syndrome： Wendantang modified with Tianwang Buxindan， ③ Heart and spleen deficiency syndrome： Jiuwei Zhenxin Granules or DANG's Ganmai Dazhaotang， ④ Fire heat and internal depression syndrome： Danzhi Xiaoyaosan Granules or Chaihu Longgu Mulitang， ⑤ Liver and kidney deficiency syndrome： JIANG's Buganshen Decoction. （2） Mania episode. ① Heart and liver fire hyperactivity syndrome： Zhengan Ningshen Formula， ② Phlegm heat harassing spirit syndrome： Huatan Xiehuo Dingshen decoction， Lianzhi Tongqiao Anshen decoction， Qingshen Dingkuang decoction or Qingshen Xingnao decoction， ③ Liver and gallbladder dampness-heat syndrome： Longdan Xiegantang. （3） Other syndrome types. ① Liver qi stagnation syndrome： modified Tongqiao Huoxue decoction， Shengyang Yiwei Acupuncture， ② Deficiency of kidney yang syndrome： Jingui Shenqitang， ③ Phlegm accumulation and blood stasis syndrome： modified Tongqiao Huoxue decoction， ④ Qi and Yin deficiency， stagnation of blood stasis syndrome： Xinnaoxin pills， ⑤ Syndrome of blood deficiency generating wind and fire heat harassing spirit： Fangji Dihuangtang.