ObjectiveTo explore the pathological mechanism-syndrome-treatment patterns of approved Chinese patent medicines （CPMs） that treat collateral disorders， providing a reference for the principle of "treating different diseases with the same therapy" in collateral pathology. MethodsCPMs that apply treatment strategies based on collateral disorders were identified from the Pharmacodia database by extracting information from the "efficacy" or "indications" sections of drug package inserts. A database was established to extract the names and compositions of the CPMs， as well as their indications， related traditional Chinese medicine （TCM） symptoms， disease locations （affected areas）， and pathological factors. Frequency statistics were performed. Using the Apriori algorithm， an association rule analysis was conducted on CPMs and disease-location combinations related to the top three most frequent pathological factor combinations. Core formulas for these combinations were identified and analyzed through drug network analysis and MCODE module clustering. ResultsA total of 660 CPMs targeting collateral disorders were retrieved， involving 299 indications， 323 TCM symptoms， 21 disease locations， 19 pathological factors， and 124 pathological factor combinations. The most frequent pathological factor combinations were blood stasis （involved in 109 CPMs， 16.52%）， exogenous wind （外风） -cold-dampness （involved in 43 CPMs， 6.52%）， and qi deficiency-blood stasis （involved in 42 CPMs， 6.36%）. Analysis of the core formulas for these combinations revealed common ingredients such as Honghua （Carthami Flos）， Chuanxiong （Chuanxiong Rhizoma）， Danggui （Angelicae Sinensis Radix）， and Dilong （Pheretima）. ConclusionCollateral disorders involve a wide range of pathogenesis and represent a fundamental mechanism in the onset and development of various diseases， characterized by obstruction and stagnation. The primary therapeutic principle is unblocking of the collaterals. Blood stasis obstructing the collaterals is the core pathological basis， and the strategy of activating blood circulation and resolving stasis to unblock the collaterals should be central to the treatment. The core medication pattern involves combining blood-activating and stasis-resolving herbs with insect-derived medicinals that unblock collaterals. Exogenous wind is often the initiating patholo-gical factor in colla-teral disorders， and the appropriate addition of wind-dispelling herbs can enrich the treatment strategies for such conditions.

Objective:To summarize the incidence of cerebral venous reflux (CVR) in patients with recent small subcortical infarct (RSSI) and explore its correlation with enlarged perivascular spaces (EPVS).Methods:Patients with RSSI in the lenticulostriate artery admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2022 were included. The baseline demographic data, medical history, and laboratory results of the patients were collected. CVR was assessed by time-of-flight magnetic resonance angiography. Patients were stratified into 2 groups based on the presence (CVR group) or absence of CVR (non-CVR group), and baseline characteristics as well as laboratory test results were compared between the 2 groups. The location and number of EPVS were evaluated using a visual grading scale, with EPVS with higher scores defined as high-grade EPVS (HEPVS). Simultaneous evaluation of cerebral white matter hyperintensities and lacunar infarctions was conducted, followed by intergroup comparisons. The relationship between EPVS and CVR was studied using multiple Logistic regression analysis.Results:A total of 571 patients with RSSI in the lentiform artery area were ultimately included, including 180 females (31.5%). Their age was (59.37±12.87) years. Among them, 73 patients (12.8%) exhibited CVR based on imaging findings, so the incidence of CVR was 12.8%. In comparison between the CVR group ( n=73) and the non-CVR group ( n=498), the proportion of females [21.9% (16/73) vs 32.9% (164/498), χ 2=3.578, P=0.059] was lower and the proportion of history of smoking [38.4% (28/73) vs 27.7% (138/498), χ 2=3.499, P=0.061] was higher in the CVR group, but without statistical significance. Additionally, the history of alcohol consumption [34.2% (25/73) vs 21.7% (108/498), χ 2=5.621, P=0.018] and the proportion of patients with concomitant HEPVS in the basal ganglia area [41.1% (30/73) vs 25.3% (126/498), χ 2=7.999, P=0.005] was higher in the CVR group with statistical significance. Multiple Logistic regression analysis showed that HEPVS in the basal ganglia region remained independently associated with CVR ( OR=1.988, 95% CI 1.190-3.320, P=0.009). Conclusion:EPVS in the basal ganglia region is significantly associated with CVR in the RSSI population, suggesting that venous dysfunction may be closely related to the formation of EPVS.

BACKGROUND:Cellular senescence is closely related to the development and progression of osteoarthritis,but the specific targets and regulatory mechanisms are not yet clear. OBJECTIVE:To mine key genes in cellular senescence-mediated osteoarthritis by integrating bioinformatics and machine learning approaches and validate them via experiments to explore the role of cellular senescence in osteoarthritis. METHODS:The osteoarthritis gene expression profiles obtained from the GEO database were intersected with cellular senescence-related genes obtained from the CellAge database and the expression of the intersected genes was extracted for differential analysis,followed by GO and KEGG analysis of the differential genes.The key osteoarthritis cellular senescence genes were then screened by protein-protein interaction network analysis and machine learning,and in vitro cellular experiments were performed.Finally,the expression of the key genes was detected by qPCR. RESULTS AND CONCLUSION:A total of 31 osteoarthritis cell senescence differential genes were identified.GO analysis showed that these genes were mainly involved in the biological processes,such as regulation of leukocyte differentiation,monocyte differentiation,regulation of T cell differentiation and exerted roles in DNA transcription factor binding,histone deacetylase binding,chromatin DNA binding,and chemokine binding.KEGG analysis showed that osteoarthritis cell senescence differential genes were mainly activated in the JAK/STAT signaling pathway,PI3K/Akt signaling pathway and FoxO signaling pathway.MYC,a key gene for osteoarthritis cellular senescence,was identified by protein-protein interaction network topology analysis and machine learning methods.The results of the in vitro cellular assay showed that the mRNA expression of MYC was significantly lower in the experimental group(osteoarthritis group)than the control group(normal group)(P＜0.05).To conclude,MYC can be a key gene in the senescence of osteoarthritic cells and may be a new target in the prevention and treatment of osteoarthritis by mediating immune response,inflammatory response and transcriptional regulation.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objective To explore the characteristics and correlation of the chin and airway in females with skeletal Class Ⅱ mandibular retraction for reference for clinical diagnosis and therapy.Methods This study was approved by the hospital Medical Ethics Committee.Forty cases of skeletal Class Ⅱ mandibular retraction adult females with aver-age angle were selected as the research group,and sixty cases of skeletal Class Ⅰ patients with average angle were se-lected as the control group.Cone-beam computed tomography(CBCT)images for all subjects were analyzed using three-dimensional modeling software.Measurements included the chin morphology,position,and upper airway morphology.Results Compared with skeletal Class Ⅰ patients,patients with skeletal Class Ⅱ mandibular retraction had smaller an-terior chin thickness,base bone volume,chin total volume,and larger chin angle,chin depression,chin curvature,and alveolar area with statistically significant differences(P＜0.05).Gn-V,Gn-H,Po-NB distance,and facial angle were smaller,and the Y-axis angle was larger in patients with skeletal Class Ⅱ mandibular retraction with statistically signifi-cant differences(P＜0.05).Upper airway total volume,transverse and sagittal diameter of the glossopharynx upper boundary were smaller in patients with skeletal Class Ⅱ mandibular retraction with statistically significant differences(P＜0.05).The correlation analysis between the morphology and position of the chin and the morphology of the upper airway in patients with Class Ⅱ mandibular retraction showed that there was a negative correlation between chin angle and laryngopharynx length in patients with Class Ⅱ mandibular retraction(r=-0.277,P＜0.01).There was a negative correlation between Po-NB distance and palatopharyngeal length(r=-0.222,P＜0.05).Chin height(r=-0.261,P＜0.01)and basal bone area(r=-0.225,P＜0.05)were negatively correlated with the transverse diameter of the palato-pharyngeal upper boundary.The minimum chin thickness(r=0.245,P＜0.05),chin angle(r=0.249,P＜0.05),and al-veolar area(r=0.213,P＜0.05)were positively correlated with the sagittal diameter of the palatopharyngeal upper boundary.Gn-V(r=0.217,P＜0.05)and Po-NB distance(r=0.208,P＜0.05)were positively correlated with the trans-verse diameter of the glossopharynx upper boundary.Anterior chin thickness was negatively correlated with the sagittal diameter of the laryngopharynx upper boundary(r=-0.211,P＜0.05).Chin depression was negatively correlated with the sagittal diameter of the laryngopharynx lower boundary(r=-0.237,P＜0.05).Chin curvature was positively corre-lated with the transverse diameter of the laryngopharynx lower boundary(r=0.231,P＜0.05).Conclusion Patients with skeletal Class Ⅱ mandibular retraction exhibit thinner chins.The sagittal position of the chin is backward,and the vertical position is upward.Patients with skeletal Class Ⅱ mandibular retraction have a narrow glossopharyngeal airway.There is a correlation between the morphology and position of the chin and the morphology of the upper airway in pa-tients with Class Ⅱ mandibular retraction.

O'Donnell-Luria-Rodan(ODLURO)syndrome is an autosomal dominant genetic disorder caused by mutations in the KMT2E(lysine methyltransferase 2E)gene.The Third Xiangya Hospital of Central South University admitted a 12-year and 9-month-old male patient who presented with growth retardation,intellectual disability,and distinctive facial features.Peripheral blood was collected from the patient,and DNA was extracted for genetic testing.Chromosome karyotyping showed 46XY.Whole-exome sequencing and low-coverage massively parallel copy number variation sequencing(CNV-seq)revealed a 506 kb heterozygous deletion in the 7q22.3 region,which includes 6 genes,including KMT2E.The patient was diagnosed with ODLURO syndrome.Both the patient's parents and younger brother had normal clinical phenotypes and genetic test results,indicating that this deletion was a de novo mutation.The clinical and genetic characteristics of this case can help increase clinicians'awareness of ODLURO syndrome.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective To analyze the characteristics of time in range(TIR)and its relationship with oxidative stress(OS)and insulin resistance status(HOMA-IR)in patients with type 2 diabetes mellitus(T2DM)and sleep apnea-hypopnea syndrome(OSAHS).Methods According to apnea-hypopnea index(AHI),165 T2DM in patients were divided into simple T2DM group(AHI<5 times/h,n=43),T2DM combine OSAHS mild group(OSAHS-G,5≤AHI<15 times/h,n=51),T2DM combined OSAHS moderate group(OSAHS-M,15≤AHI≤30 times/h,n=40)and T2DM combine OSAHS severe group(OSAHS-S,AHI>30 times/h,n=31).TIR was calculated by dynamic blood glucose monitoring.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and other indexes were detected and analyzed.Results Compared with simple T2DM group,the levels of HOMA-IR,8-iso-PGF2a and Ox-LDL were higher in T2DM combined OSAHS-G,OSAHS-M or OSAHS-S group,while the levels of TIR,SOD and GSH-Px were lower(P<0.05).Pearson correlation analysis showed that TIR was positively correlated with the levels of SOD and GSH-Px(P<0.05 or P<0.01),and negatively correlated with the levels of 8-iso-PGF2a,Ox-LDL,HbA1c,HOMA-IR and the severity of OSAHS(P<0.01).Logistic regression analysis showed that TIR,SOD and GSH-Px were protective factors for severe OSAHS in T2DM patients,while 8-iso-PGE2a and Ox-LDL were the risk factors for severe OSAHS.Conclusions The glucose level fluctuates greatly in patients with T2DM and OSAHS.Insulin resistance and oxidative stress are factors that affect the normalization of TIR.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

Objective:To evaluate the effect of wrist-ankle acupuncture on the pharmacodynamics of remimazolam for loss of consciousness in the patients of different genders and ages undergoing painless gastroscopy.Methods:American Society of Anesthesiologists Physical Status classificationⅠor Ⅱ patients, undergoing elective painless gastroscopy, were divided into 4 groups according to gender and age: agedmale (age≥65 yr) group (group AM), agedfemale (age≥65 yr) group (group AF), young male (18 yr≤age <65 yr) group (group YM), and young female (18 yr≤age <65 yr) group (group YF). After 10 min of wrist-ankle acupuncture on 1st and 2nd areas of the bilateralupper limbs of the patient, modified Dixon′s up-and-down sequential experiment was used for the test.The initial dose of intravenous remimazolam was 0.20 mg/kg. Each time the dose increased/decreased by 0.05 mg/kg. If the patient lost consciousness, the next patient received a lower dose of remimazolam, otherwise a higher dose was given in the next patient. Loss of consciousness was defined as MOAA/S score was 0 or 1, and the process was repeated until 7 turning points appeared.The median effective dose (ED 50)and 95% confidence interval of remimazolam were calculated by probit method. Results:The ED 50 and 95% confidence interval of remimazolam were 0.296(0.233-0.376), 0.319(0.262-0.388), 0.323(0.278-0.375) and 0.344(0.285-0.415)mg/kg in AM, AF, YM and YF groups, respectively. There was no significant difference in ED 50 among the four groups ( P>0.05). Conclusions:Under the action of wrist-ankle acupuncture, the pharmacodynamics of remazolam is comparable when used for the patients of different genders and ages undergoing painless gastroscopy.