The exploration and pilot studies of applying blockchain to drug supply chain show great potential in promoting information sharing, collaboration competence among the actors, regulatory efficiency, and etc. In the future, with the help of blockchain, the optimization of the entire supply chain for orphan drugs is expected to be realized. However, there is no such exploration in China at present. This paper systematically sorts out the whole process of supply chain for orphan drugs and the existing problems of the chain. The article concludes that at present, blockchain is mainly used in the " circulation" and " use" of the drug supply chain. It helps to improve the traceability of drugs, to cope with the problem of counterfeit drugs, to enable actors of the drug supply chain to form a collaborative network in optimizing resource allocation, and to improve the operation and supervision efficiency of the supply chain. In the future, the application faces challenges such as high costs in system conversion, lack of personnel awareness, and incomplete supporting systems. Based on the three dimensions of technology, practice, and research, this paper also looks into the future and suggests for the future use of blockchain in the supply chain of orphan drugs by constructing a practice model, the so called DI-GIVE (Digital, Intelligence, Government′s supervision, Innovation, Views of variety, Evaluation-based) hoping to innovate the supply chain of orphan drugs and to ensure the drug use for the patients with rare diseases in China.

OBJECTIVE To establish an HPLC fingerprint of Xiao’er resuqing oral liquid， and to determine the contents of twelve index components. METHODS HPLC method was adopted. The determination was performed on Venusil MP C18 column with mobile phase consisting of acetonitrile-0.1% phosphate aqueous solution （gradient elution） at a flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm， the column temperature was 30 ℃， the injection volume was 10 μL. HPLC fingerprint of Xiao’er resuqing oral liquid was established by using the Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition） to evaluate the similarity. The contents of 12 components were determined， including （R， S）-goitrin， 3，5-O-dicaffeoyl quinic acid， puerarin， forsythin， forsythoside A， chlorogenic acid， baicalin， saikosaponins d， wogonoside， baicalein， emodin and chrysophanol. RESULTS The similarity of HPLC fingerprints of 13 batches of Xiao’er resuqing oral liquid was greater than 0.97， and 14 common peaks were confirmed. The contents of the above 12 index components in 13 batches of Xiao’er resuqing oral liquid were as follows： 0.078-0.172， 1.564-2.736， 1.338-2.578， 0.426-0.872， 1.477-2.628， 1.396-2.447， 4.052-9.146， 0.367- 0.692， 1.974-4.674， 1.274-2.969， 0.085-0.167 and 0.155-0.307 mg/mL. CONCLUSIONS The established HPLC fingerprint and content determination methods have high accuracy and high specificity， which can be used for the quality evaluation of Xiao’er resuqing oral liquid.

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSC^M2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl₄）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSC^M2. The rats were given subcutaneous injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSC^M2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl₄. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSC^M2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSC^M2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSC^M2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl₄/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

BACKGROUND:Hypoxic exercise can promote the degradation of body fat,and changes in the external environment can affect the circadian rhythm of animals,but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear. OBJECTIVE:To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise. METHODS:Forty obese rats were randomly selected and divided into four groups(n=10 per group):normoxic sedentary group,hypoxic sedentary group,normoxic exercise group,and hypoxic exercise group for 4 weeks of intervention.The rats in the sedentary groups were not intervened,while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6%for the whole day.In the exercise groups,adaptive training was performed in the 1st week,and the speed and length of training remained unchanged for the last 3 weeks.The body mass,body length and perirenal fat mass of obese rats were measured.Serum levels of triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit.Liver fat content was observed by oil red O staining.Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups.RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue.The mRNA expressions of PGC-1α,Beclin 1,KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR. RESULTS AND CONCLUSION:Hypoxic exercise intervention significantly decreased body mass,body fat percentage,Lee's index,serum triacylglycerol,total cholesterol,and low-density lipoprotein cholesterol levels(P＜0.01),and significantly increased high-density lipoprotein cholesterol level(P＜0.01).Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liver tissue and promoting the browning of parepididymal adipose tissue compared with normoxic sedentary group,hypoxic sedentary group,and normoxic exercise group.RNA-seq results showed that hypoxic exercise significantly upregulated the expression of clock genes Dbp,Nr1d1,Sik1 and adipose tissue browning gene Ppargc1a(PGC-1α)and downregulated the expression of Arntl(Bmal1),accompanied by the enhanced expression of genes related to substance metabolism.qRT-PCR indicated that hypoxic exercise significantly increased the mRNA expression levels of PGC-1α and Perilipin1(P＜0.01).Therefore,these findings indicate that clock genes play an important role in promoting adipose tissue browning during hypoxic exercise.

Objective It aims to construct a quality evaluation index system for cancer multidisciplinary diagnosis and treatment(MDT)model in China from a full process perspective,providing guidance for practical application and model optimization.Methods Based on the number of MDT publications and practical situations,20 provincial-level hospitals nationwide were selected as typical cases.Rooted theory was used to extract evaluation indicators from the original text of the cases through three-level coding.A cancer MDT quality evaluation index system was constructed under the Input-Process-Output framework.Results Through three-level coding,27 initial categories,8 subcategories,and 3 main categories were sorted out,and a cancer MDT quality evaluation index system was constructed with input,process,and output as the primary evaluation indicators,and top-level design,management system,object resources,meeting preparation,meeting progress,plan implementation,patient outcomes,and hospital outcomes as the secondary evaluation indicators.Conclusion The quality evaluation index system of cancer MDT mode based on the perspective of the entire process can effectively guide practical optimization,but there is still a need for the improvement of supporting policies and information systems to assist in quality evaluation.

Objective To investigate the effect and mechanism of Yiguan Decoction(YGJD)on the efficacy of M1 bone marrow-derived macrophages(M1-BMDMs)in the treatment of rats with liver cirrhosis induced by 2-AAF/CCl4.Methods BMDMs were isolated and induced into M1-BMDMs by lipopolysaccharide.A total of 50 male Wistar rats were randomly divided into normal group with 5 rats and model group with 45 rats.The rats for modeling were given subcutaneous injection of 50%CCl4 twice a week.Since week 7,the rats for modeling were randomly divided into model group(M group),YGJD group,M1-BMDM group,M1-BMDM+YGJD group,and sorafenib(SORA)group,and they were given subcutaneous injection of 30%CCl4 to maintain the progression of liver cirrhosis and intragastric administration of 2-AAF.CCR2 inhibitors were added to the drinking water,and each group was given the corresponding intervention.Related samples were collected at week 9.The rats were observed in terms of serum liver function parameters,liver pathology,hydroxyproline(Hyp)content in liver tissue,hepatic stellate cell activation,hepatic fibrosis and inflammation factors,and the expression levels of molecules associated with the Wnt signaling pathway.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the M group,the M1-BMDM+YGJD group had significant reductions in the serum levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin(TBil)(all P<0.05)and a significant increase in the content of albumin(Alb)(P<0.05),and compared with the M1-BMDM group,the M1-BMDM+YGJD group had a significant reduction in the serum level of TBil(P<0.05)and a significant increase in the serum level of Alb(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in the expression levels of CD68 and TNF-α(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in Hyp content and Sirius red positive area(P<0.05).As for the non-canonical Wnt signaling pathway molecules,compared with the M1-BMDM group,the M1-BMDM+YGJD group had significantly lower mRNA and protein expression levels of Wnt5a(P<0.05)and mRNA expression level of Fzd2(P<0.05),as well as significant reductions in the mRNA expression levels of Wnt4,Wnt5b,and Fzd3(P<0.05),while there were no significant changes in the mRNA expression levels of the canonical Wnt signaling pathway molecules β-catenin,LRP5,LRP6,Fzd5,and TCF.Conclusion YGJD can enhance the therapeutic effect of M1-BMDMs on rats with liver cirrhosis induced by 2-AAF/CCl4,possibly by inhibiting the non-canonical Wnt5a/Fzd2 signaling pathway,which provides new ideas for the synergistic effect of traditional Chinese medicine on M1-BMDMs in the treatment of liver cirrhosis.

Objective:To explore the application of anterior esophageal wall full layer fixation and gastric tube guidance in total laparoscopic overlap method for intracorporeal esophagojejunostomy.Methods:Overlap esophagojejunostomy with anterior esophageal wall full layer fixation and gastric tube guidance is suitable for patients with advanced gastric cancer (clinical stage: cT1b~4aN0~3M0) and esophageal invasion <3 cm, who underwent radical total gastrectomy+ overlap esophagojejunostomy. The main operation procedure was performed as follows: A titanium clip was used for fixation of the full anterior wall of esophagus before overlap esophagojejunostomy, and the side‐to‐side esophagojejunostomy was performed with the linear stapler under the guidance of gastric tube. Then the titanium clip was removed after confirming that the correct cavity was entered. Finally, the common outlet was closed by two barbed sutures. A descriptive case series study was conducted. The clinical data of patients who underwent laparoscopic radical gastrectomy and overlap esophagojejunostomy with anterior esophageal wall full layer fixation and gastric tube guidance in Guangdong Provincial Hospital of Chinese medicine and the First Affiliated Hospital of Guangzhou University of Chinese medicine from May 2021 to June 2023 were retrospectively analyzed.Results:A total of 42 patients were collected, and all of them were successfully completed laparoscopic total radical gastrectomy without conversion to laparotomy or perioperative death. The esophagojejunostomy time, operative time, intraoperative blood loss was 17(5‐25) minutes, (258.8±38.0) minutes and 50(20‐200) ml, respectively. The incidence of esophageal false lumen was 0%, and there were no intraoperative complications. The time of gastric tube removal, initial fluid diet intake and the duration of postoperative hospital were 2(1‐5) , 4(1‐8) and 8(4‐21) days, respectively. There were no postoperative anastomotic hemorrhage, anastomotic stenosis and other related complications. One patient (2.38%) developed a Clavien‐Dindo IIIb complication, which was abdominal hemorrhage after operation. The second surgical exploration confirmed that the patient was bleeding due to gastroduodenal artery rupture. After intraoperative suture hemostasis, fluid expansion, blood transfusion and other treatments, the patient was discharged on the 15th day after the operation. Three patients (7.14%) developed Clavien‐Dindo grade II complications, including anastomotic leakage, chylous leakage and pulmonary infection, and were discharged after conservative treatment such as anti‐infection and prolonged retention of drainage tube.Conclusions:Laparoscopic overlap method for intracorporeal esophagojejunostomy with anterior esophageal wall fixation and gastric tube guidance can shorten the time of esophagojejunostomy and prevent the occurrence of false lumen, and do not increase anastomose‐related complications.

Objective:To analyze the clinical features and genetic etiology of 17 Chinese pedigrees affected with X-linked intellectual disability (XLID).Methods:Seventeen pedigrees affected with unexplained intellectual disability which had presented at Henan Provincial People′s Hospital from May 2021 to May 2023 were selected as the study subjects. Clinical data of the probands and their pedigree members were collected. Trio-whole exome sequencing (Trio-WES), Sanger sequencing and X chromosome inactivation (XCI) analysis were carried out. Pathogenicity of candidate variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics and co-segregation analysis.Results:The 17 probands, including 9 males and 8 females with an age ranging from 0.6 to 8 years old, had all shown mental retardation and developmental delay. Fourteen variants were detected by genetic testing, which included 4 pathogenic variants ( MECP2: c. 502C>T, MECP2: c. 916C>T/c.806delG, IQSEC2: c.1417G>T), 4 likely pathogenic variants ( MECP2: c. 1157_1197del/c.925C>T, KDM5C: c. 2128A>T, SLC6A8: c. 1631C>T) and 6 variants of uncertain significance ( KLHL15: c. 26G>C, PAK3: c. 970A>G/c.1520G>A, GRIA3: c. 2153C>G, TAF1: c. 2233T>G, HUWE1: c. 10301T>A). The PAK3: c.970A>G, GRIA3: c. 2153C>G and TAF1: c. 2233T>G variants were considered as the genetic etiology for pedigrees 12, 14 and 15 by co-segregation analysis, respectively. The proband of pedigree 13 was found to have non-random XCI (81: 19). Therefore, the PAK3: c. 1520G>A variant may underlie its pathogenesis. Conclusion:Trio-WES has attained genetic diagnosis for the 17 XLID pedigrees. Sanger sequencing and XCI assay can provide auxiliary tests for the diagnosis of XLID.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Photon Counting Detector(PCD)is a device used to detect X-ray photons,which can directly convert the energy of photons into electrical signals to achieve photon counting and measurement.PCD-based energy spectrum computed tomography(PCD-CT)technology can provide additional energy spectral imaging information,and improve imaging quality while reducing radiation dose.Compared with energy integrating detectors(EID),PCD has advantages of high energy conversion efficiency,good imaging quality,exquisite structural design,and wide application range.It has broad application prospects in ultra-low-dose CT,specific disease diagnosis,and industrial inspection.The application of PCD-CT in spectral CT imaging was reviewed to provide a useful reference for its application in clinical medical diagnosis and industrial applications.