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.

ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

ObjectiveTo elucidate the potential mechanism of modified Sinisan （MSNS） in alleviating anxiety-like behaviors induced by chronic restraint stress （CRS） in mice at the metabolic level based on serum untargeted metabolomics and identify key metabolites and metabolic pathways regulated by MSNS. MethodsSeventy-two male C57BL/6 mice were randomly assigned into six groups： control， model， high-dose （2.4 g·kg^-1） MSNS， medium-dose （1.2 g·kg^-1） MSNS， low-dose （0.6 g·kg^-1） MSNS， and positive control （fluoxetine， 2.6 mg·kg^-1）. Except the control group， the other groups were subjected to CRS for the modeling of anxiety. Mice were administrated with corresponding agents by gavage 2 h before daily restraint for 14 days. Anxiety-like behaviors were evaluated by the open field test （OFT）， elevated plus maze （EPM） test， and light/dark box （LDB） test. Serum levels of corticotropin-releasing hormone （CRH）， adrenocorticotrophic hormone （ACTH）， and corticosterone （CORT） were measured via ELISA to assess stress levels. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was employed to detect 9 metabolites in the brain tissue and serum metabolites. Orthogonal partial least squares-discriminant analysis （OPLS-DA） was adopted to identify differential metabolites （VIP>1.0， P<0.05）. MetaboAnalyst 5.0 was used for metabolic pathway enrichment analysis of the differential metabolites. ResultsCompared with the control group， the model group showed reductions in the central activity time and central distance in the OFT （P<0.05）， the proportions of open-arm residence time and open-arm residence times in the EPM test （P<0.01）， and the proportions of open box activity time and open box activity distance in the LDB test （P<0.05）， which were increased in the medium- and high-dose MSNS groups compared with the model group （P<0.05）. Compared with the control group， the model group showed elevated levels of CRH， ACTH， and CORT in the serum （P<0.01）， and the elevations were diminished in the medium- and high-dose MSNS groups （P<0.05）. UPLC-MS results indicated that compared with the control group， the model group presented declined DA， GABA， 5-HIAA， 5-HT， and 5-HT/Trp levels （P<0.05， P<0.01） and raised Glu， NE， Kyn， and Kyn/Trp levels （P<0.05）. Compared with the model group， high-dose MSNS increased the GABA， 5-HIAA， and 5-HT/Trp levels （P<0.05） and lowered the Glu and Kyn/Trp levels （P<0.05）. Untargeted metabolomics identified that 16 CRS-induced metabolic disturbances were reversed by MSNS. KEGG pathway analysis indicated that MSNS primarily modulated eight core pathways including alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， TCA cycle， unsaturated fatty acid biosynthesis， and tryptophan metabolism. The mechanisms involved multidimensional biological processes， including neurotransmitter homeostasis regulation， TCA cycle energy metabolism optimization， and inflammatory response suppression. ConclusionMSNS alleviates CRS-induced anxiety-like behaviors in mice by mitigating hypothalamic-pituitary-adrenal axis hyperactivity， improving hippocampal neurotransmitter and tryptophan metabolic pathways， and regulating alanine/aspartate/glutamate metabolism， butyrate metabolism， arginine-proline metabolism， and TCA cycle.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

Objective:To investigate the clinical effect of super-thin free anterolateral thigh (ALT) flap at the junction plane of superficial and deep fat of superficial fascia to repair the soft tissue defects of the foot.Methods:The clinical data of patients with foot soft tissue defects admitted to Northern Jiangsu People’s Hospital Affiliated to Yangzhou University from June 2017 to December 2022 were retrospectively analyzed. During the operation, the super-thin free ALT flap on the affected side was harvested at the junction of superficial and deep fat of superficial fascia to repair the foot wound. The donor site wound was sutured directly or repaired with full-thickness skin graft. The flap survival and complications were observed after the operation, and the operation effect was evaluated from the following five aspects. (1) The Maryland foot function score was used to evaluate the recovery of foot function. The full score was 100 points, of which 90-100 points were excellent, 75-89 points were good, 50-74 points were fair, and < 50 points were poor. (2) The Vancouver scar scale (VSS) was used to evaluate the scar condition of the foot. The total score was 0-15 points. The higher the score, the more serious the scar. (3) The cold intolerance symptom severity (CISS) scale was used to evaluate the cold tolerance of the affected foot. The total score was 4-100 points. The higher the score, the more serious the symptoms. (4) Measuring static two-point discrimination to evaluate foot sensation, the smaller the measured value, the better the sensory recovery. (5) The satisfaction of patients with foot appearance was investigated, which was divided into five grades: very satisfied, satisfied, general, dissatisfied and very dissatisfied. Descriptive analysis of the data was performed using SPSS 26.0 software.Results:A total of 13 patients with foot soft tissue defects were enrolled, including 8 males and 5 females. The mean age was 54.7 years (range, 39-70 years). There were 10 cases of left foot and 3 cases of right foot. The wound area after thorough debridement ranged from 5.5 cm ×5.0 cm to 22.0 cm ×18.0 cm. The operation time was (145.1 ± 30.6) min. The area of the flap was 6.0 cm×5.5 cm to 23.5 cm×19.0 cm, and the thickness was (5.2 ± 1.1) mm (range, 3.0- 6.5 mm). The wound at the donor site was sutured directly in 9 cases, and coverd with the abdominal full-thickness skin graft in 4 cases. After the operation, 1 patient had partial epidermal necrosis at the distal end of the flap, 1 patient had venous crisis.The flaps survived after symptomatic treatment. The remaining 11 flaps survived smoothly. The patients were followed up for 12 to 20 months, with an average of 16 months. The foot flaps were soft and free of damage, and no secondary fat reduction or plastic surgery was required. There were no complications such as wound dehiscence, skin graft necrosis, muscle hernia, and quadriceps weakness in 13 cases of donor site except for hypoesthesia caused by scar hyperplasia in 4 cases with skin graft. At the last follow-up, the Maryland foot function score was (87.4±7.3) points, of which 7 cases were excellent, 4 cases were good, and 2 cases were fair. The excellent and good rate was 11/13. The foot scar was not obvious, the VSS score was (3.2±1.2) points. The foot was more tolerant to cold and the sensory recovery was better, the CISS score was (37.5±7.1) points and the static two-point discrimination was (13.9±1.0) mm. One month after the operation, the results of patients’ satisfaction with foot appearance were as follows: 11 cases were very satisfied and 2 cases were satisfied.Conclusion:The super-thin free ALT flap is obtained at the junction plane of superficial and deep fat of superficial fascia to repair the soft tissue defect of the foot, which can optimize the operation time. The appearance and function of the foot recover well after the operation, avoiding the secondary shaping operation, reducing the damage to the donor site, and the patients are satisfied.

Objective:To investigate the clinical effect of super-thin free anterolateral thigh (ALT) flap at the junction plane of superficial and deep fat of superficial fascia to repair the soft tissue defects of the foot.Methods:The clinical data of patients with foot soft tissue defects admitted to Northern Jiangsu People’s Hospital Affiliated to Yangzhou University from June 2017 to December 2022 were retrospectively analyzed. During the operation, the super-thin free ALT flap on the affected side was harvested at the junction of superficial and deep fat of superficial fascia to repair the foot wound. The donor site wound was sutured directly or repaired with full-thickness skin graft. The flap survival and complications were observed after the operation, and the operation effect was evaluated from the following five aspects. (1) The Maryland foot function score was used to evaluate the recovery of foot function. The full score was 100 points, of which 90-100 points were excellent, 75-89 points were good, 50-74 points were fair, and < 50 points were poor. (2) The Vancouver scar scale (VSS) was used to evaluate the scar condition of the foot. The total score was 0-15 points. The higher the score, the more serious the scar. (3) The cold intolerance symptom severity (CISS) scale was used to evaluate the cold tolerance of the affected foot. The total score was 4-100 points. The higher the score, the more serious the symptoms. (4) Measuring static two-point discrimination to evaluate foot sensation, the smaller the measured value, the better the sensory recovery. (5) The satisfaction of patients with foot appearance was investigated, which was divided into five grades: very satisfied, satisfied, general, dissatisfied and very dissatisfied. Descriptive analysis of the data was performed using SPSS 26.0 software.Results:A total of 13 patients with foot soft tissue defects were enrolled, including 8 males and 5 females. The mean age was 54.7 years (range, 39-70 years). There were 10 cases of left foot and 3 cases of right foot. The wound area after thorough debridement ranged from 5.5 cm ×5.0 cm to 22.0 cm ×18.0 cm. The operation time was (145.1 ± 30.6) min. The area of the flap was 6.0 cm×5.5 cm to 23.5 cm×19.0 cm, and the thickness was (5.2 ± 1.1) mm (range, 3.0- 6.5 mm). The wound at the donor site was sutured directly in 9 cases, and coverd with the abdominal full-thickness skin graft in 4 cases. After the operation, 1 patient had partial epidermal necrosis at the distal end of the flap, 1 patient had venous crisis.The flaps survived after symptomatic treatment. The remaining 11 flaps survived smoothly. The patients were followed up for 12 to 20 months, with an average of 16 months. The foot flaps were soft and free of damage, and no secondary fat reduction or plastic surgery was required. There were no complications such as wound dehiscence, skin graft necrosis, muscle hernia, and quadriceps weakness in 13 cases of donor site except for hypoesthesia caused by scar hyperplasia in 4 cases with skin graft. At the last follow-up, the Maryland foot function score was (87.4±7.3) points, of which 7 cases were excellent, 4 cases were good, and 2 cases were fair. The excellent and good rate was 11/13. The foot scar was not obvious, the VSS score was (3.2±1.2) points. The foot was more tolerant to cold and the sensory recovery was better, the CISS score was (37.5±7.1) points and the static two-point discrimination was (13.9±1.0) mm. One month after the operation, the results of patients’ satisfaction with foot appearance were as follows: 11 cases were very satisfied and 2 cases were satisfied.Conclusion:The super-thin free ALT flap is obtained at the junction plane of superficial and deep fat of superficial fascia to repair the soft tissue defect of the foot, which can optimize the operation time. The appearance and function of the foot recover well after the operation, avoiding the secondary shaping operation, reducing the damage to the donor site, and the patients are satisfied.

Objective:To explore the clinical phenotype and genetic etiology for a Chinese pedigree affected with Autosomal dominant polycystic kidney disease (ADPKD).Methods:A pedigree with ADPKD diagnosed at the Department of Gynaecology of the First Affiliated Hospital of Zhengzhou University in December 2020 was selected as the study subject. Clinical data of the pedigree was collected, and whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing of the proband and her relatives. This study was approved by the First Affiliated Hospital of Zhengzhou University (Ethics No. KS-2018-KY-36).Results:Fetal ultrasonography showed increased volume and parenchymal echogenicity in both kidneys. The fetus was found to harbor c. 11098C>T (p.R3700C) and c.11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene, which were respectively inherited from its mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1+ PM2_Supporting+ PP3). Conclusion:The c. 11098C>T (p.R3700C) and c. 11039T>C (p.F3680S) compound heterozygous variants of the PKD1 gene probably underlay the ADPKD in the fetus. Above finding has provided guidance for the genetic counseling and prenatal diagnosis for this pedigree.

Objective To describe the incidence and mortality of brain tumors in China in 2020 and to predict the disease burden up to 2040.Methods The brain tumor incidence and mortality in 2020 were recorded based on the data from International Agency for Cancer Research(IARC),Cancer Today database.The incidence and mortality were standardized by age using Segi's world standard population.The burden of brain tumors in 2040 was predicted with assuming that national rates remained constant in 2020.Results It was estimated there were approximately 79 600 new brain tumors cases and 65 200 deaths in China in 2020.The age-standardized incidence and mortality rates of brain tumors in China were 4.1/100 000 and 3.2/100 000,respectively,which were lower than the United States of America,most of European countries and Australia.The incidence and mortality were higher than Africa,central America,and the Caribbean.From 2020 to 2040,the brain tumors cases and deaths are predicted to have an increase as 32.1%and 41.5%respectively.Conclusions The disease burden of brain tumors was still heavy in China.Further studies are urgently needed to clarify the epidemic trend of tissue typing and risk factors of brain tumors,which may support the development of effective prevention strategies.

Objective:To study positive rates and typing of oligoclonal bands (OCB) in patients with neurological disorders, and to reveal the clinical significance and applicational value of OCB test.Methods:A retrospective analysis was performed on the detection results of 3 217 patients with neurological disorders who undertook both serum and cerebrospinal fluid OCBs in the First Hospital of Peking University from January 2012 to August 2022. According to the final diagnosis, the patients were divided into 13 groups including multiple sclerosis (479 cases), neuromyelitis optica spectrum disorders (935 cases), autoimmune encephalitis (192 cases), viral encephalitis (94 cases), nervous system complication after HSCT (232 cases), Guillain-Barré syndrome (644 cases), chronic inflammatory demyelinating polyneuropathy (157 cases), etc. Cerebrospinal fluid and serum OCBs were detected using isoelectric focusing electrophoresis combining immunofixation, then classified into Ⅰ-Ⅴ types according to the morphology. Consequently, positive rates and types were analyzed for each group. χ2 test was used for comparison between groups. Results:The positive rates of cerebrospinal fluid OCB in multiple sclerosis, nervous system complication after hematopoietic stem cell transplantation (HSCT), autoimmune encephalitis, viral encephalitis, neuromyelitis optica spectrum disorders, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy were respectively 66.8% (320/479), 48.7% (113/232), 46.4%(89/192), 19.1% (18/94), 17.6% (165/935), 9.9% (64/644), 5.1% (8/157). For patients with multiple sclerosis, neuromyelitis optica spectrum disorders, viral encephalitis, and autoimmune encephalitis, Type Ⅱ bands took the majority of cerebrospinal fluid OCB-positive cases with the rates of 94.1% (301/320), 78.7% (70/89), 77.8% (14/18), and 77.6% (128/165) respectively, indicating intrathecal IgG synthesis; for patients with nervous system complication after HSCT, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, type Ⅳ bands took the majority of cerebrospinal fluid OCB-positive cases with the rates of 94.7% (107/113), 82.8% (53/64) and 100% (8/8), indicating no obvious intrathecal IgG synthesis. The positive rates of cerebrospinal fluid oligoclonal bands were significantly different among all groups (χ 2=1 268.31, P<0.001). Conclusion:The positive rates of cerebrospinal fluid oligoclonal bands are different among different neurological disorders, in which the positive rate of cerebrospinal fluid OCB is higher with type Ⅱ bands as the majority type in multiple sclerosis, which indicates that the detection and typing of cerebrospinal fluid OCB are helpful for the diagnosis of various neurological diseases, especially for multiple sclerosis.

【Objective】 To explore the role of ZFP36 in cardiomyocyte injury and autophagy induced by hypoxia/reoxygenation (H/R) so as to clarify its molecular regulatory mechanism. 【Methods】 H9C2 rat cardiomyocytes were infected with ZFP36 overexpressing lentivirus (OE-ZFP36) or its negative control lentivirus (OE-ZFP36 NC) to construct stable cell lines, respectively. Transfection of ATG4D overexpression plasmid (OE-ATG4D) improved the expression of ATG4D. Hypoxia/reoxygenation (H/R) induced myocardial cell injury. H9C2 cells were mainly divided into control group, H/R group, OE-ZFP36 NC+H/R group, OE-ZFP36+H/R group, OE-ATG4D NC+H/R group, OE-ATG4D+H/R group, OE-ZFP36+OE-ATG4D NC+H/R group, and OE-ZFP36+OE-ATG4D+H/R group. The protein expressions of ATG4D, Beclin1, LC3 and ZFP36 in H9C2 cells were detected by Western blotting. The mRNA levels of ZFP36 and ATG4D in H9C2 cells were detected by Real-time fluorescence quantitative PCR (qPCR). The viability of H9C2 cells was detected by CCK-8 assay. The levels of interleukin (IL-6) and tumor necrosis factor (TNF-α) in H9C2 cells were detected by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) in H9C2 cells were detected by DCFH-DA method. SOD detection kit was used to detect the SOD level in H9C2 cells. The apoptosis of H9C2 cells was detected by flow cytometry. LC3 autophagosomes in H9C2 cells were detected by cellular immunofluorescence. Dual-luciferase reporter gene assay was used to detect the binding of ZFP36 and ATG4D mRNA in H9C2 cells. 【Results】 Compared with control group, H/R group showed decreased cell viability, increased IL-6 and TNF-α levels, increased ROS levels and decreased SOD levels, increased cell apoptosis. Up-regulated ATG4D and Beclin1 protein expression, increased LC3Ⅱ/LC3Ⅰ ratio, as well as upregulated ZFP36 expression were found in H/R group (all P<0.05). Compared with OE-ZFP36 NC+H/R group, elevated cell viability, decreased IL-6 and TNF-α levels, decreased ROS levels and increased SOD levels, reduced cell apoptosis (P<0.05), and downregulated ATG4D and Beclin1 protein expression, decreased LC3Ⅱ/LC3Ⅰ ratio were shown in OE-ZFP36+H/R group (all P<0.05). Compared with infection with OE-ZFP36 NC lentivirus, infection with OE-ZFP36 lentivirus decreased the luciferase activity of ATG4D 3′-UTR reporter gene, decreased the stability of ATG4D mRNA, and downregulated the H/R-induced ATG4D mRNA expression (all P<0.05). Compared with OE-ATG4D NC+H/R group, OE-ATG4D+H/R group had upregulated ATG4D mRNA and protein expression, decreased cell viability, increased IL-6 and TNF-α levels, increased ROS levels, decreased SOD levels and elevated cell apoptosis (all P<0.05). Compared with OE-ZFP36+OE-ATG4D NC+H/R group, OE-ZFP36+OE-ATG4D+H/R group had decreased cell viability, increased IL-6 and TNF-α levels, increased ROS levels, decreased SOD levels and elevated cell apoptosis (all P<0.05). 【Conclusion】 The expression of ZFP36 is upregulated in H/R-induced cardiomyocyte injury. The overexpression of ZFP36 inhibits H/R-induced cardiomyocyte injury and autophagy by regulating ATG4D, thus resisting cardiomyocyte H/R injury. It proves that ZFP36 is an important regulatory molecule against MI/RI.