Chronic bronchitis （CB） is a common respiratory system disease that is classified as a lung disease in traditional Chinese medicine （TCM） and is closely related to lung dysfunction. Lung Yang is the Yang Qi of the lungs，which drives the physiological activities within the lungs. It has physiological functions such as warming the lung system，regulating lung fluid，and dispersing the protective Yang. It can be distributed on the surface of the airway's Yin skin through sweat pores in the form of airflow and fluid，playing a protective and nourishing role. If the protective Yang fails to guard the Yin skin or if the lung fluid cannot nourish the Yin skin，the structural integrity of the airway's Yin skin may be compromised. This may weaken lung Yang's functions， such as clearing phlegm turbidity，dispersing lung fluid，and resisting external pathogens. Consequently， the retention of phlegm turbidity，insufficient nourishment of the Yin skin，and invasion by external pathogens all damage the lung Yang，burn the lung fluid，and exacerbate the pathological state of Yin skin unprotected，forming a vicious cycle that ultimately results in lung Yang asthenia and then the onset of CB. Based on the intrinsic connection between "Yin skin unprotected" and "lung Yang asthenia"，this paper interprets the etiology and pathogenesis of CB. It proposes that "Yin skin unprotected" in the airway is the basic cause of CB and "lung Yang asthenia" caused by "Yin skin unprotected" is the core pathogenesis of CB. By integrating micro differentiation indicators with macro differentiation syndromes， the study explores its modern biological basis. Guided by the theory of "warming the lung Yang and protecting the Yin skin" and based on modern pharmacology research，this study further explores the scientific connotation of single TCM and compound formulations for treating TCM by warming the lung Yang and protecting the Yin skin. Furthermore， it proposes methods for dispelling pathogenic factors and protecting the Yin skin during the acute exacerbation phase，as well as nourishing and warming lung Yang during the remission phase，in order to provide new ideas for the early prevention and treatment of TCM.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

BACKGROUND: All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. METHODS: ATRA content was detected with ELISA and HPLC–MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro–computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. RESULTS: We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. CONCLUSIONS Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.

Abstract: Objective　To explore the spatial epidemiological characteristics of severe cases hand, foot and mouth disease (HFMD) in Guangxi, China, from 2014 to 2018, and to provide a basis for identifying the high-risk regions as well as the prevention and control of severe cases of HFMD in Guangxi. Methods　Spatial-temporal scanning analysis, global and local spatial autocorrelation analysis were used to analyze the spatial clustering of HFMD. The trend surface analysis was used to evaluate the spatial distribution trend of HFMD. Results　From 2014 to 2018, the incidence and severe case fatality rates of HFMD were 3.89/100 000 and 4.23%, respectively. Monte Carlo scanning analysis showed that the first cluster region was Cenxi City, the second cluster was mainly concentrated in northwest of Guangxi, and the aggregation time was mainly concentrated in April to May and August to October. The global spatial autocorrelation analysis showed that the severe HFMD was significant clustering distribution, and the Moran's I coefficients of the sever cases, severe morbidity and severe case fatality rate were 0.088, 0.118, 0.197, respectively (P<0.05). Local spatial autocorrelation analysis showed that hotspots of severe HFMD cases were concentrated in the southern Guangxi, mainly in Lingshan County. Anselin local Moran's I clustering and outlier analysis indicated that 5 high-high (H-H) clustering regions for fatality were Lingshan, Pubei, Zhongshan, Zhaoping and Pinggui County. There were 6 high-high (H-H) clustering regions for severe incidence rate, namely Lingshan, Qinnan, Lingyun, Youjiang, Bama Yao Autonomous and Pinggui County, and 1 high-low (H-L) clustering region, Cenxi County. The trend surface analysis showed that the overall number of severe cases of death decreased from east or west to the middle, and increased from north to middle, and then decreased to south. Conclusions　Severe HFMD cases in Guangxi have obvious spatial-temporal clustering, and the hop spots are mainly concentrated in southern Guangxi. The prevention and control of HFMD in areas with high incidence of severe cases should be strengthened to reduce the burden of HFMD cases.

Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.
Colorectal Neoplasms/surgery* ; Female ; Humans ; Immunotherapy ; Male ; Middle Aged ; Neoadjuvant Therapy ; Rectal Neoplasms/surgery* ; Retrospective Studies

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective:To explore the feasibility, safety and early prognosis of laparoscopic choledocholithotomy in patients with previous history of upper abdominal surgery.Methods:From January 2014 to December 2018, the clinical data of 156 patients with previous history of upper abdominal surgery in hepatobiliary and pancreatic surgery of Central Hospital of Edong Healthcare Group were analyzed retrospectively. Among them, 84 cases with laparoscopic common bile duct exploration and stone extraction were allocated into laparoscopic group, 72 cases with open common bile duct exploration and stone extraction were allocated into open group.In the laparoscopic group, there were 50 males and 34 females, aged 42-83 (66.4±17.8) years; In the open group, there were 40 males and 32 females, aged 45-82 (64.2±16.9) years. The operation time, intraoperative hemorrhage, first defecation time and postoperative hospital stay were compared between the two groups. The postoperative pain score and the incidence of early complications (bile leakage, abdominal distention, ascites, epigastric pain, residual stones) were compared between the two groups. The measurement data subject to normal distribution are represented by ( Mean± SD), the independent sample t test was used for group comparison, and the chi-square test was used for counting data comparison. Results:The laparoscopic group was converted to open surgery in 3 cases, and there was no perioperative death. In the laparoscopic group, the operation time, the intraoperative bleeding volume, the first defecation time, the postoperative hospital stay wee (122.8 ± 28.1) min, (80.3 ± 13.7) mL, (1.8 ± 0.3) d, (7.7 ± 0.8) d, and (146.6 ± 33.5) min, (125.8 ± 19.6) mL, (2.7 ± 0.6) d, (9.1± 1.2) d in the open group; The difference between the two groups was statistically significant ( P<0.05); On the 2nd and 4th day after operation, the abdominal pain scores in laparoscopic group were (3.6 ± 1.3) scores and (2.3 ± 0.7) scores, and (5.5±1.6) scores, (4.2±1.3) scores in the open group, the laparoscopic group were significantly lower than those in the open group ( P<0.05); The incidence of early postoperative complications in the laparoscopic group was 32.1% (27/84), and in the open group was 47.2% (34/72), but the difference was not statistically significant ( P>0.05). Conclusions:For patients with a history of upper abdominal surgery, laparoscopic common bile duct exploration and choledochoscopy are safe and feasible, The operation has the advantages of minimally invasive and less bleeding, which can relieve postoperative pain, shorten postoperative hospital stay, and will not increase the incidence of postoperative complications, It′s good for quick recovery. It is suitable for the promotion of grass-roots hospitals.

Three different beta-glycosidase sequences of Ttebgl3, Tpebgl1 and Tpengl3 from Thermotoga thermarum DSM 5069 and Thermotoga petrophila RKU-1 were analyzed. Also, the influence of temperature, pH, concentration of DMSO, metal ions and kinetic constant on catalytic conversion of baicalin had been compared. The results indicated that the optimal pH and optimum temperature for transformation of baicalin was 4.5 85 °C, 5.0 80 °C and 5.5 80 °C, respectively. The family GH3 beta-glycosidase Ttebgl3 and Tpebgl3 had the better DMSO tolerance. The activation effect of the metal ions on the catalytic conversion of baicalin was not obvious, and the inhibition of the GH3 family beta glucosidase was significantly stronger than that of the GH1 family. The kinetic constants of three different beta-glucosidases catalyzed baicalin were significantly different. The Km and Vmax values of Tpebgl1, Tpebgl3 and Ttebgl3 were 0.029 2 mmol·L⁻¹ 4.85 U·mg⁻¹, 0.268 6 mmol·L⁻¹ 121.04 U·mg⁻¹ and 0.391 8 mmol·L⁻¹ 308.90 U·mg⁻¹, respectively. Family GH3 beta-glycosidase converted more baicalin than family GH1 with the optimal conditions, 0.02 g baicalin, and the conversion rate was 68%, 97.3%, 97.31% respectively. The results of the study provided a guarantee for the transformation of baicalin.

AIM:To explore the expression level of long non-coding RNA(lncRNA)myocardial infarction-as-sociated transcript(MIAT)in the tissues and cells of non-small-cell lung carcinoma(NSCLC), and to investigate the effect of MIAT on the function of NSCLC cell line.METHODS:Bioinformatic data in microarray dataset GSE19804 from Gene Expression Omnibus(GEO)were collected for analyzing the difference expression of MIAT between NSCLC tissues and normal lung tissues.Clinical and prognostic data in microarray dataset GSE 30219 from GEO were also collected for an-alyzing the correlation between the expression level of MIAT and the survival time of NSCLC patients.qPCR was applied to detect the expression of MIAT in 25 paired tumor tissues and corresponding adjacent normal tissues,normal lung epithelial HBE cell line and NSCLC A549,NCI-H266 and NCI-H1299 cell lines.The specific small interfering RNA for MIAT(si-MIAT group)or negative control sequence(si-NC group)was transfected into A549 cells,and flow cytometry,colony for-mation experiment and CCK-8 assay were employed to detect the proliferation of the cells in the 2 groups.The expression levels of cyclin D1 and cyclin-dependent kinase inhibitor 1A(CDKN1A)in the 2 groups were determined by qPCR and Western blot.RESULTS:In the GEO dataset GSE19804,the expression of MIAT in NSCLC tissues was significantly ele-vated compared with normal lung tissues(P<0.05).In the GEO dataset GSE30219,the overall survival time was signifi-cantly shorter in the patients with high expression of MIAT than the patients with low expression of MIAT(P<0.05).Fur-thermore,the levels of MIAT in both NSCLC tissues and cells were higher than those in adjacent normal tissues and normal cells(P<0.05).Compared with si-NC group,lower MIAT level,cell viability and cell colony number in si-MIAT group with statistical significance were observed(P<0.05).Meanwhile, compared with si-NC group, the expression of cyclin D1 in si-MIAT group was significantly decreased(P<0.05),and inversely,the expression of CDKN1A in si-MIAT group was significantly increased(P<0.05).CONCLUSION:There is high expression of MIAT in NSCLC tissues and NSCLC cells,and knockdown of MIAT expression inhibits NSCLC cell proliferation, which provides a potential target of targeted therapy for NSCLC.