The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Based on the pathogenesis of “tendon off-position and joint subluxation”， combined with modern ana-tomy and biomechanics， the characteristic manifestations of “tendon off-position” and “joint subluxation” of the knee and the intrinsic connection between them are clarified. Through sorting out the relationship between “tendon off-position and joint subluxation” and knee osteoarthritis （KOA） in modern research， it is believed that “tendon off-position and joint subluxation” is the key mechanism for the occurrence and development of KOA， and accordingly， it is proposed to take the diet as the guide， use bone manipulation for external diagnosis and treatment， use traditional Chinese medicine decoction for internal treatment， and use Daoyin exercise throughout the whole process as the strategy for KOA's comprehensive traditional Chinese medicine treatment to improve the clinical effectiveness.

BACKGROUND:"Tendon off-position"is a disease name included in the International Classification of Diseases 11th Revision,and also a clinical indication of manipulation,acupuncture and other treatments.However,its specific mechanism is still unclear.It is urgent to establish an animal model that can reflect the clinical and pathological characteristics of"tendon off-position,"so as to further study the mechanism of effective clinical treatments. OBJECTIVE:To establish an animal model of"tendon off-position"in rats based on isometric contraction of skeletal muscles,and to explore the changes of skeletal muscle function and morphological phenotype after"tendon off-position." METHODS:Sixty rats were randomly divided into control group,static-loading group and extra loading group,with twenty rats in each group.Rats in the control group were kept normally without treatment.In the latter two groups,the rats were fixed by the self-made static-loading modeling device and a static-loading(the body mass of each rats was applied as the static-loading)was applied to cause sustained isometric contraction of the upper limb muscles.Then,animal models of"tendon off-position"were successfully established.In the extra loading group,50%of the body mass was added to the ankle joint after modeling.The skeletal muscle samples were harvested at 2 and 4 weeks after modeling.The changes of limb grip strength,wet mass of skeletal muscle,and serum levels of creatine kinase-muscle and lactate dehydrogenase A were measured,and the changes of skeletal muscle histomorphology and ultrastructure were observed. RESULTS AND CONCLUSION:At 2 weeks after modeling,the rats in the static-loading group and extra loading group showed significantly decreased grip strength and wet muscle mass,significantly increased serum levels of creatine kinase-muscle and lactate dehydrogenase A,and abnormal muscle fiber morphology and structure accompanied by a large number of deposited collagen fibers.Electron microscopy results showed that the structure of myofibrils was disordered,the Z-line was distorted,and the light and dark boundaries were blurred.At 4 weeks after modeling,the grip strength of the model rats was increased compared with that at 2 weeks,the serum creatine kinase-muscle and lactate dehydrogenase A levels were decreased,and the changes of muscle fiber morphology and ultrastructure were recovered to varying degrees.It is suggested that the rat skeletal muscle injury model based on continuous isometric contraction of skeletal muscle can well reflect the pathological characteristics of"tendon off-position"at 2 weeks,and can be used to study the mechanism of acupuncture and manipulation in the treatment of"tendon off-position."

Objective To investigate the effect of intravitreal injection of fibrillin-2(FBN2)recombinant protein on FBN2-deficient retinopathy.Methods Thirty-two SPF-grade C57BL/6J mice were randomly divided into 4 groups:nor-mal control group,negative control group,FBN2 knockdown group,and FBN2 recombinant protein group,with 8 mice in each group.The right eyes were taken as the experimental eyes.Mice in the normal control group did not receive any inter-vention,mice in the negative control group were intravitreally injected with 3 μL empty vector(1 mg·L-1),and mice in the FBN2 knockdown group and FBN2 recombinant protein group were intravitreally injected with 3 μL adeno-associated vi-rus(1 mg·L-1).After 4 weeks,mice in the FBN2 recombinant protein group were intravitreally injected with 3 μL FBN2 recombinant protein(1 mg·L-1).Then,electroretinogram(ERG)and optical coherence tomography(OCT)were used to measure the amplitude of Rod-b and Max-a waves and the changes in the retinal structure.Real-time quantitative poly-merase chain reaction(RT-PCR)and Western blot were used to detect changes in FBN2,microfibril-associated glycopro-tein 2(MAGP-2),collagen I(COL1)mRNA and protein expression in the mouse retina.Results The ERG findings showed that compared with the negative control group and normal control group,the amplitude of Rod-b and Max-a waves in the retina of mice in the FBN2 knockdown group and FBN2 recombinant protein group decreased(all P＜0.05);com-pared with the FBN2 knockdown group,the amplitude of Rod-b and Max-a waves in the retina of mice in the FBN2 recom-binant protein group significantly increased(both P＜0.05).The OCT findings showed that compared with the FBN2 knock-down group,the structure of the retinal pigment epithelium and the light reflex in the FBN2 recombinant protein group be-came more regular.The RT-PCR detection results showed that compared with the FBN2 knockdown group,the expression of FBN2 mRNA in the retinal tissue of mice in the FBN2 recombinant protein group significantly increased,while the ex-pression of COL1 and MAGP-2 mRNA significantly decreased(all P＜0.05).Western blot assay results showed that com-pared with the FBN2 knockdown group,the expression of FBN2 protein in the retinal tissue of mice in the FBN2 recombi-nant protein group increased significantly,while the expression of COL1 and MAGP-2 proteins decreased significantly(all P＜0.05).Conclusion Intravitreal injection of FBN2 recombinant protein can compensate for the endogenous deficiency of FBN2 in mice with FBN2-deficient retinopathy and achieve therapeutic effects by regulating COL1 and MAGP-2 expres-sion.

Objective:To investigate the expression of latent transforming growth factor-β-binding protein (LTBP), transforming growth factor-β (TGF-β), cyclin-dependent kinase 2 (CDK2) and cyclin D2 (CCND2) in fibrillin-2 ( FBN2) interfering induced mouse retinopathy. Methods:Twenty-seven 8-week-old C57BL/6J mice were randomly divided into normal control group, empty vector group and FBN2 interference group according to the random number table method, with 9 mice in each group.The normal control group was not treated.The empty vector group and FBN2 interference group were intravitreally injected with 3 μl empty vector and 3 μl adeno-associated virus (AAV) carrying the sh-FBN2 interference plasmid in the right eye, respectively.The structural and functional changes of the retina were detected at 4 weeks after injection by optical coherence tomography (OCT) and full-field electroretinography (ERG).The expression and distribution of FBN2 protein in the retina were detected by immunofluorescence staining.The mRNA and protein expression levels of FBN2, LTBP-1, TGF-β2, CDK2 and CCND2 in mouse retina were detected by real-time fluorescence quantitative PCR and Western blot.All experiments complied with the ARVO statement.The research scheme was approved by the Experimental Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (No.2019036).Results:Four weeks after injection, the results of OCT examination showed that compared with normal control and empty vector groups, the retinal pigment cortex of the FBN2 interference group was irregular with high density reflection areas.Full-field ERG results showed that compared with normal control and empty vector groups, the amplitude of Rod-a, Rod-b, Max-a and Max-b waveforms in FBN2 interference group decreased, and the differences were statistically significant (all at P<0.05).The results of immunofluorescence staining showed that FBN2 was expressed in the whole retina, and the fluorescence intensity of FBN2 was weaker in FBN2 interference group than that in normal control and empty vector groups.The fluorescence intensity of FBN2 in normal control group, empty vector group and FBN2 interference group was 16.21±2.21, 15.57±3.63 and 5.32±1.06, respectively, with a statistically significant overall difference ( F=66.03, P<0.05).The fluorescence intensity of FBN2 protein in FBN2 interference group was significantly lower than that in empty carrier group and normal control group (both at P<0.05).Compared with normal control and empty vector groups, the relative expression levels of LTBP-1 and TGF-β2 mRNA and protein were significantly increased in FBN2 interference group, while the relative expression levels of FBN2, CDK2 and CCND2 mRNA and protein were significantly decreased, and the differences were statistically significant (all at P<0.05). Conclusions:The increase of LTBP-1 and TGF-β2 and the decrease of G1/S phase related proteins CDK2 and CCND2 are involved in the development of FBN2-deficient retinopathy.

Objective To simultaneously collect and analyze the kinematic and dynamic parameters for two techniques of traditional Chinese cervical manipulation ( TCCM), and quantitatively describe its biomechanical characteristics. Methods A senior practitioner completed the TCCM (positioning and directional rotation pulling, lateral flexion, respectively) on 10 healthy subjects, and the fluorescent marker balls were pasted on the operator to capture manipulation movements. The dynamic parameters and the surface electromyography ( sEMG) signals were collected by pressure-sensitive gloves and wireless sEMG acquisition system. Results The upper arm muscle was the main force muscle during TCCM, and biceps brachii had the highest contribution rate. The range of motion (ROM), speed, pulling force, and time during cervical spine positioning and directional rotation pulling were all greater than those during cervical spine lateral flexion. The integrate electromyography ( iEMG) and root mean square (RMS) for each muscle of the operator during cervical spine positioning and directional rotation pulling were higher than those during cervical spine lateral flexion. Conclusions The overall ROM, three-dimensional (3D) motion angle, load intensity and time during CCTM have the characteristics of high speed, low amplitude and strong force, reflecting the biomechanical characteristics of ‘ cunjin ’ ( one-inch punch ) in traditional Chinese medicine. This study provides references for further standardizing manual teaching and training and improving clinical safety.

OBJECTIVE To study th e pharmacodynamics and pha rmacokinetics of Qinglian ningxin capsule in rats with ischemic arrhythmia. METHODS Totally 30 male SD rats were randomly divided into blank control group ，model control group ， Qinglian ningxin capsule group （4.00 g/kg），Artemisia annua group（1.43 g/kg），Coptis chinensis group（0.42 g/kg），with 6 rats in each group. Administration groups were given relevant medicine intragastrically ；model control group and blank control group were given normal saline intragastrically ，once a day ，for consecutive 7 days. After last medication ，except for blank control group，other groups were given Posterior pituitary injection via tail vein （1 u/kg） to induce ischemic arrhythmia model. electrocardiogram changes of rats in each group were recorded. Another 36 rats were randomly divided into Qinglian ningxin capsule model group and Qinglian ningxin capsule control group （4.00 g/kg），A. annua model group and A. annua control group （1.43 g/kg），C. chinensis model group and C. chinensis control group （0.42 g/kg）. After the rats in each model group were injected with Posterior pituitary injection （1 u/kg）via tail vein ，administration groups were given relevant drugs intragastrically ， and control groups were given constant volume of normal saline intragastrically. Blood was taken from the orbit at different time points（0，0.25，0.75，1，2，4，6，8，12 and 24 h）. The concentrations of berberine hydrochloride and artemisinin in plasma were determined by HPLC ，and the pharmacokinetic parameters were calculated by WinNonlin 7.0 software. RESULTS Compared with the model control groups ，Qinglian ningxin capsule could significantly improve the heart rate slowing of rats and redu ced the prolongation of PR interval and QT interval significantly ，and the effects were generally better than those of A. annua group and C. chinensis group（P＜0.05）. Compared with A. annua control group and C. chinensis control group ，cmax，AUC0－t and AUC 0－∞ of berberine hydrochloride and artemisinin were increased significantly in Qinglian ningxin capsule control group，while CL was decreased significantly ；t1/2z of artemisinin was prolonged significantly （P＜0.05）. Compared with Qinglian ningxin capsule control group ，cmax（except artemisinin ），AUC0－t，AUC0－∞，MRT0－t and MRT 0－∞（except artemisinin ）of berberine hydrochloride and artemisinin were increased significantly in Qinglian ningxin capsule model group ，while CL was decreased significantly（P＜0.05）. CONCLUSIONS Qinglian ningxin capsule could significantly improve ischemic arrhythmia better than A. annua and C. chinensis ，and can improve the absorption of berberine hydrochloride and artemisinin in model rats and slow down their elimination.

Objective:To explore risk factors for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-ALL).Methods:A retrospective analysis was performed for 65 adult Ph-ALL patients undergoing initial allo-HSCT from 2016 to 2018. The effect of baseline level and treatment pre-transplantation for relapse after allo-HSCT was analyzed.Results:There were 37 males and 28 females with a median age of 25(14-58) years during allo-HSCT. And the median follow-up period was 27 months post-HSCT. The 2-year overall survival (OS) was 78.8%(95%CI 67.8%-89.8%) and the 2-year relapse-free survival (RFS) 70.7% (95%CI 58.2%-83.2%). Pre-transplant chemotherapy was offered for 3 to 7 courses and the median dose of polyethylene glycol-conjugated asparaginase (PEG-ASP) was 3 doses (2 000 IU/m 2 per dose). Multiariate analysis revealed that the regimen included more than 4 doses of PEG-ASP pre-HSCT (HR=4.067, P=0.046) was a protective factor for post-transplant relapse (HR=0.193, P=0.009). High-risk chromosome karyotype was a risk factor for relapse (HR=0.193, P=0.009). The 2-year RFS rate was 90.0%(95%CI 79.2%-100.0%) for intensive PEG-ASP group and 56.9%(95%CI 39.1%-74.7%) for control group ( P=0.01). No significant inter-group difference existed in overall survival (OS)( P=0.079). The 2-year OS was 90.6% (95%CI 80.4%-100.0%) in intensive PEG-ASP group and 72.1% (95%CI 56.6%-87.6%) in control group. Conclusions:For adult ph-ALL patients, a higher dose of PEG-ASP in pretransplant chemotherapy regimens may improve post-transplant RFS and achieve a better outcome.

BACKGROUND: Low dose computed tomography (LDCT) for lung cancer screening is widely employed in China as a result of increasing cancer screening awareness. Although some pulmonary lesions detected by LDCT are cancerous, most of the pulmonary nodules are benign. It is important to make effective preoperative differentiation of pulmonary lesions and to obviate the need for surgery in some patients with benign disease. METHODS: From January 1, 2017 to December 31, 2018, patients in our institution with surgical pathology confirmed benign pulmonary lesions in which malignancy could not be excluded in preoperative assessment were enrolled in this study. Retrospective analysis of clinical data was conducted. RESULTS: 297 cases were collected in this study. Prevalence of benign disease in patients underwent resection for focal pulmonary lesions is 9.8% in our institution. In 197 patients (66.3%), pulmonary lesions were detected by LDCT screening. A total of 323 assessable pulmonary lesions were detected by chest CT. The average diameter of pulmonary lesions was (17.9±12.1) mm, and 91.0% of which were greater than or equal to 8 mm. Solid nodules accounted for 65.6% of these lesions. Imaging characteristics suggesting malignancy were common, including spicule sign (71/323, 22.0%), lobulation (94/323, 29.1%), pleural indentation (81/323, 25.1%), vascular convergence sign (130/323, 40.2%) and vacuole sign (23/323, 7.1%). 292 patients (98.3%) underwent video-assisted thoracoscopic surgery (VATS). Pulmonary wedge resection was performed in 232 cases (78.1%), segmental resection in 13 cases (4.4%) and lobotomy in 51 cases (17.2%). Surgical complications occurred in 4 patients (1.3%). The most frequent findings on surgical pathology analysis were: infectious lesions in 98 cases (33.0%), inflammatory nodules in 96 cases (32.3%), and hamartoma in 64 cases (21.5%). CONCLUSIONS Solid nodules accounted for most of these benign pulmonary lesions in which malignancy could not be excluded preoperatively, and imaging characteristics suggesting malignancy were common. VATS is an important biopsy method to identify etiology and pathology for lesions. The most frequent benign pulmonary diseases that are suspected to be malignant and underwent surgical resection are: infectious lesions, inflammatory nodules and hamartoma.