ObjectiveAccording to the theory of medicinal properties in traditional Chinese medicine （TCM）， Tangye Jingfa Tu， implying that all tonic prescriptions should primarily feature sweetness. However， the "Chart of the Classic Methods of Decoction Therapy" recorded in Mnemonic Aids for Medical Practice （Fuxingjue） proposes that each of the Zangfu organs has a corresponding tonifying flavor， i.e.， pungent for the liver， salty for the heart， sweet for the spleen， sour for the lungs， and bitter for the kidneys. Therefore， deficiency syndromes of different organs should be primarily addressed with specific medicinal flavors. This study applies this theoretical framework to analyze the formulation and compatibility principles and efficacy positioning of commonly used TCM tonic prescriptions， providing a reference for differentiated clinical medication. MethodsA database of tonic prescriptions was established based on the textbook Science of Prescriptions. Excel software was used to separately calculate the number of medicinal types， frequency of use， flavors， and proportional composition of the prescriptions. The prescriptions were categorized to determine their compatibility structures and functional characteristics. ResultsA total of 60 prescriptions were included， classified into six categories， involving 110 medicinal types with 469 instances of use. From the perspective of the "Chart of the Classic Methods of Decoction Therapy"， different tonic prescriptions exhibit distinct dominant medicinal flavors and organ associations. Specifically， 15 Qi-tonifying prescriptions primarily adopted a "sweet flavor" to tonify the spleen. Nine blood-tonifying prescriptions primarily adopted a "pungent-salty flavor" to tonify the liver and heart. Seven Qi-and-blood-tonifying prescriptions primarily featured a "sweet-pungent flavor" to tonify the spleen and liver. Nineteen Yin-tonifying prescriptions primarily adopted a "bitter-sour flavor" to tonify the kidneys and lungs. Seven Yang-tonifying prescriptions primarily featured a "pungent-bitter flavor" to tonify the liver and kidneys. Three Yin-and-Yang-tonifying prescriptions primarily featured a "bitter-pungent-sweet flavor" to tonify the kidneys， liver， and spleen. ConclusionThe "Chart of the Classic Methods of Decoction Therapy" clearly illustrates the formulation and compatibility principles and key differences among various tonic prescriptions， indicating that not all tonic prescriptions are predominantly sweet in flavor. This provides new insights for the clinical modification and application of tonic prescriptions.

ObjectiveAccording to the theory of medicinal properties in traditional Chinese medicine （TCM）， Tangye Jingfa Tu， implying that all tonic prescriptions should primarily feature sweetness. However， the "Chart of the Classic Methods of Decoction Therapy" recorded in Mnemonic Aids for Medical Practice （Fuxingjue） proposes that each of the Zangfu organs has a corresponding tonifying flavor， i.e.， pungent for the liver， salty for the heart， sweet for the spleen， sour for the lungs， and bitter for the kidneys. Therefore， deficiency syndromes of different organs should be primarily addressed with specific medicinal flavors. This study applies this theoretical framework to analyze the formulation and compatibility principles and efficacy positioning of commonly used TCM tonic prescriptions， providing a reference for differentiated clinical medication. MethodsA database of tonic prescriptions was established based on the textbook Science of Prescriptions. Excel software was used to separately calculate the number of medicinal types， frequency of use， flavors， and proportional composition of the prescriptions. The prescriptions were categorized to determine their compatibility structures and functional characteristics. ResultsA total of 60 prescriptions were included， classified into six categories， involving 110 medicinal types with 469 instances of use. From the perspective of the "Chart of the Classic Methods of Decoction Therapy"， different tonic prescriptions exhibit distinct dominant medicinal flavors and organ associations. Specifically， 15 Qi-tonifying prescriptions primarily adopted a "sweet flavor" to tonify the spleen. Nine blood-tonifying prescriptions primarily adopted a "pungent-salty flavor" to tonify the liver and heart. Seven Qi-and-blood-tonifying prescriptions primarily featured a "sweet-pungent flavor" to tonify the spleen and liver. Nineteen Yin-tonifying prescriptions primarily adopted a "bitter-sour flavor" to tonify the kidneys and lungs. Seven Yang-tonifying prescriptions primarily featured a "pungent-bitter flavor" to tonify the liver and kidneys. Three Yin-and-Yang-tonifying prescriptions primarily featured a "bitter-pungent-sweet flavor" to tonify the kidneys， liver， and spleen. ConclusionThe "Chart of the Classic Methods of Decoction Therapy" clearly illustrates the formulation and compatibility principles and key differences among various tonic prescriptions， indicating that not all tonic prescriptions are predominantly sweet in flavor. This provides new insights for the clinical modification and application of tonic prescriptions.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Objective:To explore the role of conducting a"thematic morning report"based on post-competency in the standardized residents training in hospital in the Intensive Care Unit(ICU).Methods:A total of 60 resident training physicians who participated in the standardized residents training in hospital in the ICU of this hospital from January 2020 to December 2022 were included,and randomly divided into an observation group and a control group,with 30 in each group.The observation group adopted an interactive teaching method of themed morning report based on post-competency,while the control group adopted the traditional teaching method.The assessment results of clinical theoretical knowledge and operational skills of the two groups of resident training physicians under different teaching methods were compared.The 360°assessment method was used to record the multi-directional evaluation of patients or their families,nurses,colleagues,and teaching teachers on the post-competence of resident training physicians(self-learning ability,team collaboration ability,effective communication ability,and learning interest).Results:The assessment scores of clinical theoretical knowledge and practical skills in the observation group after teaching were higher than those in the control group,with statistically significant differences(theoretical assessment:t=2.101,P＜0.05;practical assessment:t=9.647,P＜0.05).The post-competence scores of nurses,colleagues,and teaching teachers on resident training physicians in the observation group were higher than those in the control group after one-month regular training,and the differences were statistically significant(nurses'evaluation of self-learning ability:t=3.182,P=0.002,team collaboration ability:t=3.978,P＜0.05,effective communication ability:t=2.180,P=0.0335,learning interest:t=3.884,P＜0.05;colleagues'evaluation of self-learning ability:t=2.888,P=0.005,team cooperation ability:t=6.816,P＜0.05,effective communication ability:t=3.833,P＜0.05,learning interest:t=4.086,P＜ 0.05;teaching teacher's evaluation of self-learning ability:t=3.429,P=0.001,team cooperation ability:t=3.086,P=0.003,effective communication ability:t=3.493,P=0.001,learning interest:t=3.126,P=0.003).There was a statistically significant difference in the satisfaction scores of patients or their familymembers towards the two groups of resident training physicians(t=3.126,P=0.003).Conclusion:The use of the interactive teaching method of thematic morning report based on post-competency in the standardized residents training in hospital in the ICU can not only improve the theoretical practice and case analysis test scores of resident training physicians,but also improve the post-competence and the satisfaction of patients and their families.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

Background: and Purpose CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature. Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeatprimed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats. Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients. Conclusions Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

We here investigated the effect of MS4A6D(the membrane spanning 4-domain subfamily A(MS4A)superfamily protein 6D),one of the tetraspanins which specifically expresses on the membrane of macrophages,on carrageenan(CGN)-induced mouse foot pad swelling and its possible mechanism.Male C57BL/6 wild-type(WT)and various gene knockout(including Ms4a6d-/-,Nlrp3-/-,Casp-1-/-and IlR1-/-)mice were recruited and injected with 100 μl 1%CGN(w/v)and 20 μl CaCl2(50 mmol/L)to establish the foot pad swelling model,and then the severity of foot pad swelling in WT and gene knockout mice were compared.H&E staining was performed to investigate the pathological changes,and immunofluorescence was used to detect the infiltration of F4/80+ macrophages in the foot pad tissue.Finally,Western blot was used to determine the protein expression of NLRP3,IL-1 β,TNF-α and IL-6.Data showed that the combined injection of 100 μl 1%CGN(w/v)and 20 μl CaCl2(50 mmol/L)significantly promoted the swelling of foot pads,while the degree of foot pad swelling in Ms4a6d-/-mice was significantly lower than that in WT littermates(P<0.05);Significant tissue damage and inflammatory infiltration as well as necrotic lesions were observed in the WT foot pads,whereas,the degrees from Ms4a6d-/-foot pads showed significantly reduced;The protein levels of Caspase-1 and IL-1β in the foot pad tissue of the WT model were significantly higher than those of the Ms4a6d-/-groups;Compared with WT controls,the degree of foot pad swelling in Nlrp3-/-,Casp-1-/-,and IlR1-/-mice induced by 1%CGN(w/v)and CaCl2(50 mmol/L)were also significantly reduced(P<0.05).Taken together,MS4A6D promotes the activation of NLRP3 inflammasome in macrophages and induces IL-1β secretion,by thus deteriorates CGN-mediated swelling of mouse foot pads.

Objective:To explore the effect of sports training guidance based on Internet platform on the limb function and quality of life in home rehabilitation of stroke hemiplegic patients.Methods:Eighty patients with stroke and hemiplegia admitted to Beijing Rehabilitation Hospital Affiliated to Capital Medical University from June 2018 to December 2019 were selected and divided into observation group and control group with 40 cases in each group by random digits table method. The control group was given routine rehabilitation training. In addition to the regular rehabilitation training, the observation group was supplemented with home rehabilitation based on the WeChat platform for modified constraint-induced movement therapy. The limb motor function Fugl-Meyer Assessment (FMA) score, Upper Extremity Function Test (UEFT) score, Stroke-Specific Quality of Life scale (SS-QOL) score before and after intervention, and patients′ satisfaction and cares′ satisfaction score were compared between the two groups.Results:There was no significant difference in the score of FMA, UEFT, SS-QOL before intervention between the two groups( P>0.05). After discharge, the FMA score, UEFT score and physical function, physiological function, mental health, social function of SS-QOL score were (68.87±6.64),(72.38±7.33), (35.28±4.13), (36.55±4.23), (37.22±3.84), (38.23±3.44) points in the observation group and (55.25±6.20), (61.24±6.47), (28.72±4.56), (30.85±5.30), (31.28±4.63), (31.02±5.16) points in the control group, and the differences were statistically significant between the two groups( t values were 5.316-9.482, P<0.01). During the nursing period, the patients′ satisfaction and cares′ satisfaction score were 92.50%(37/40), 87.50%(35/40) in the observation group and 72.50%(29/40), 67.50%(27/40) in the control group, and the differences were statistically significant between the two groups( χ 2 values were 5.541, 4.588, P<0.05). Conclusions:The home rehabilitation based on the Internet platform for modified constraint-induced movement therapy helps to promote the recovery of limb motor function in stroke hemiplegic patients, improve the nursing satisfaction of patients and their families, and has a positive effect on improving the quality of life of patients.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.