Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

ObjectiveTo explore the effects of Gegen Qinliantang（GGQL） on the proliferation and apoptosis of intestinal epithelial cells as well as on the expression of cyclic adenosine monophosphate （cAMP）， G protein-coupled receptor 119 （GPR119）， and glucagon-like peptide-1 （GLP-1）， so as to explore its potential hypoglycemic mechanism. MethodTwenty-five Wistar rats were gavaged with GGQL at the dose of 23 g·kg^-1 crude drug， twice a day， which meant that 6 mL was administered into each rat per day for preparing the GGQL-containing serum. After seven consecutive times of administration， the intestinal epithelial L （NCI-H716） cells were cultured with different concentrations （1%， 2.5%， 5%， 7.5%， and 10%） of GGQL. The cell proliferation was evaluated using cell counting kit-8 （CCK-8） and the apoptosis by flow cytometry. The GLP-1 and cAMP contents in cell supernatant were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein GLP-1 and GPR119 levels were assayed by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the control group， GGQL significantly reduced the proliferation of NCI-H716 cells（P<0.05）. As the GGQL concentration increased， its inhibitory effect became more obvious. GGQL at each concentration significantly promoted the apoptosis of NCI-H716 cells （P<0.05）. Compared with the control group， GGQL significantly up-regulated the expression of cAMP， GLP-1， and GPR119 （P<0.05）. The results showed that the effect of GGQL was positively correlated with its concentration， and 10% GGQL exhibited the best effect. ConclusionGGQL effectively inhibits the proliferation of NCI-H716 cells and promotes their apoptosis， and it may promote the secretion of GLP-1 by up-regulating the expression of cAMP and GPR119.

Aim To investigate the effects of combined administration of loganin and berberine on bone structure and metabolism in diabetic mice and its potential mechanism.Methods The diabetic ICR mouse model was induced by high fat diet(HFD).After 10 weeks of combined intervention, the effects of loganin and berberine on body weight, body fat rate, blood glucose, blood lipid and serum oxidative stress levels were observed.Bone microstructure was scanned by micro-CT.Biomechanical characteristics of bone were measured by three-point bending test, and material properties were detected by fourier transform infrared(FTIR).The pathological changes were observed by HE and TRAP staining.Protein expressions involved in advanced glycation end products(AGEs)and their receptors(RAGE)/nuclear factor-κB(NF-κB)signaling pathway were detected by immunohistochemistry.Results The combined administration of loganin and berberine could significantly inhibit the weight gain, reduce the levels of blood glucose, blood lipid and oxidative stress, as well as improve glucose tolerance.In addition, combined intervention also decreased the expression levels of the proteins involved in AGEs/RAGE/NF-κB signaling pathway, and improved bone microstructure, finally contributing to increasing bone quality in diabetic mice.Conclusions The combination of loganin and berberine could improve bone metabolism in diabetic mice, which may be related to AGEs/RAGE/NF-κB signaling pathway.

The chemical constituents in the volatile oil of Syringa oblata were identified using GC-MS and NIST database. TCMSP and SwissTargetPrediction were employed to predict the potential targets of the active components in S. oblata. Through Online Mendelian Inheritance in Man(OMIM), GeneCards, and Kyoto Encyclopedia of Genes and Genomes(KEGG), we screened out the targets related to the prevention or treatment of angina pectoris by the volatile oil of S. oblata, and then used DAVID 6.8 to annotate the gene ontology(GO) terms and KEGG pathways. The "active components-targets-pathways" network was constructed in Cytoscape 3.6.0, and the key active components and targets of S. oblata were verified by Discovery Studio 2016. Forty-six chemical constituents were identified from the volatile oil of S. oblata; 198 potential targets of the active components and 1 138 targets associated with angina pectoris were predicted. A total of 71 common targets were shared by the active components and the disease, including cytochrome P450 19 A1(CYP19 A1) and prostaglandin G/H synthase 2(PTGS2). The KEGG pathways involved include PPAR, JAK-STAT, TNF, Toll-like receptor and NOD-like receptor signaling pathways. The active components in the volatile oil of S. oblata may play anti-inflammatory and anti-apoptosis roles. This study provides a reliable clue for further explanation of the effective components and the functioning mechanism of S. oblata in the treatment of angina pectoris.
Angina Pectoris ; Drugs, Chinese Herbal/pharmacology* ; Gas Chromatography-Mass Spectrometry ; Humans ; Molecular Docking Simulation ; Network Pharmacology ; Syringa

Aim: To identify the key risk factors of intrauterine hepatitis B virus transmission (HBV) and its effect on the placenta and fetus. Methods: 425 infants born to hepatitis B surface antigen (HBsAg)-positive pregnant women who received combined immunization with hepatitis B immunoglobulin and hepatitis B vaccine between 2009 to 2015 were prospectively enrolled in this study. The intrauterine transmission situation was assessed by dynamic monitoring of infants HBV DNA load and quantitative HBsAg. Univariate and multivariate regression analysis was used to determine the high risk factors for intrauterine transmission. Stratified analysis was used to determine the relationship between maternal HBV DNA load and fetal distress. Transmission electron microscopy was used to observe HBV Effects on placental tissue. Results: HBV intrauterine infection rate was 2.6% (11/425). Multivariate analysis result showed that the maternal HBV DNA load was an independent risk factor for intrauterine infection among infants (P=0.011). Intrauterine infection and distress rate was significantly higher in infants with with maternal HBV DNA>10⁶ IU/ml than those with HBV DNA <10⁶ IU/ml (12.2% vs. 1.8%; χ²=11.275, P=0.006), and (24.4% vs. 16.0%, χ²=3.993, P=0.046). Transmission electron microscopy showed that mitochondrial edema, endoplasmic reticulum expansion and thicker basement membrane were apparent when the maternal HBV DNA>10⁶ IU/ml than that of maternal HBV DNA<10⁶ IU/ml (960 nm vs. 214 nm, Z=-2.782, P=0.005) in the placental tissue. Conclusion: Maternal HBV DNA>10⁶ IU/ml is associated not only with intrauterine infection, but also with increased incidence of intrauterine distress and placental sub-microstructural changes, providing strong clinical and histological evidence for pregnancy avoidance and treatment in this population.
DNA, Viral ; Female ; Fetal Distress/drug therapy* ; Hepatitis B/prevention & control* ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines/therapeutic use* ; Hepatitis B virus/genetics* ; Humans ; Immunoglobulins/therapeutic use* ; Infant ; Infectious Disease Transmission, Vertical/prevention & control* ; Placenta ; Pregnancy ; Pregnancy Complications, Infectious

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

OBJECTIVE: To study the clinical features of neuroblastoma (NB) and the factors influencing survival rate. METHODS: A total of 44 children with NB who were admitted from April 2016 to February 2020 were enrolled as research subjects. A retrospective analysis was performed on their medical data and follow-up data. RESULTS: The common clinical symptoms of these 44 children were fever (10/44, 23%), mass (9/44, 20%), abdominal pain (8/44, 18%), cough (7/44, 16%), pale complexion (3/44, 7%), claudication (2/44, 5%), and abnormal activity (2/44, 5%). According to the INSS stage, 2 children (4%) had stage I NB, 5 children (11%) had stage II NB, 5 children (11%) had stage III NB, and 32 children (73%) had stage IV NB. The mean follow-up time was (15.3±1.5) months, with a recurrence rate of 20% and an overall survival rate of 82%. Among the 44 children, 29 (66%) achieved event-free survival and 7 (16%) had survival with tumor. The univariate analysis showed that a pathological type of NB and an increase in serum neuron-specific enolase (NSE) decreased the overall survival rate of children with NB (P<0.05). CONCLUSIONS The clinical symptoms of children with NB are not specific at the first visit. Fever, abdominal pain, and mass are common symptoms, and there is a high proportion of children in the advanced stage. The pathological type of NB and an increase in serum NSE may be associated with a reduction in the overall survival rate of children with NB.
Child ; Humans ; Infant ; Infant, Newborn ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neuroblastoma ; Phosphopyruvate Hydratase ; Retrospective Studies ; Survival Rate

Objective::To establish HPLC fingerprints of Aurantii Fructus and its processed products, and to quantitatively analyze the contents of four flavonoids in these products. Method::HPLC was employed with Inertsil ODS-3 C₁₈ column (4.6 mm×250 mm, 5 μm), the mobile phase of acetonitrile-0.1%phosphoric acid aqueous solution for gradient elution, the detection wavelength of 283 nm, and the flow rate of 1.0 mL·min^-1. HPLC fingerprints of raw products, stir-fried bran products and processing products of Aurantii Fructus were established. Similarity evaluation and cluster analysis were used to analyze the chromatographic data. At the same time, the contents of narirutin, naringin, hesperidin and neohesperidin were determined. Result::HPLC fingerprints of Aurantii Fructus and its processed products were established, taking naringin as the reference peak, 8, 15, 11 common peaks were demarcated for raw products, stir-fried bran products, processing products, respectively, the similarities of fingerprints were >0.95.Contents of the above four flavonoids in raw products were 0.574 7%, 5.986 3%, 0.302 2%and 3.574 7%, respectively. After processing, the contents of these four components in stir-fried bran products turned into 0.948 4%, 5.103 4%, 0.549 3%and 3.533 7%, their contents in processing products turned into 0.605 3%, 4.762 3%, 0.404 7%and 3.264 9%, respectively. Conclusion::The HPLC fingerprint of Aurantii Fructus changes significantly before and after processing. The contents of four flavonoids change to a certain extent before and after processing. The order of contents of narirutin and hesperidin in samples was stir-fried bran products>processing products>raw products, while the order of contents of naringin and neohesperidin was raw products>stir-fried bran products>processing products.