ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveMetabolomics was utilized to investigate the preventive effect of notoginseng total saponins（NTS） on aspirin（acetyl salicylic acid， ASA）-induced small bowel injury in rats. MethodFifty male SD rats were randomly divided into normal and model groups， NTS high-dose and low-dose groups（62.5， 31.25 mg·kg^-1）， and positive drug group（omeprazole 2.08 mg·kg^-1+rebamipide 31.25 mg·kg^-1）， with 10 rats in each group. Except for the normal group， rats in other groups were given ASA enteric-coated pellets 10.41 mg·kg^-1 daily to establish a small intestine injury model. On this basis， each medication group was gavaged daily with the corresponding dose of drug， and the normal group and the model group were gavaged with an equal amount of drinking water. Changes in body mass and fecal characteristics of rats were recorded and scored during the period. After 14 weeks of administration， small intestinal tissues of each group were taken for hematoxylin-eosin（HE） staining， scanning electron microscopy to observe the damage， and the apparent damage of small intestine was scored. Serum from rats in the normal group， the model group， and the NTS high-dose group was taken and analyzed for metabolomics by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the data were processed by multivariate statistical analysis， the potential biomarkers were screened by variable importance in the projection（VIP） value≥1.0， fold change（FC）≥1.5 or ≤0.6 and t-test P<0.05， and pathway enrichment analysis of differential metabolites was performed in conjunction with Human Metabolome Database（HMDB） and Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultAfter 14 weeks of administration， the average body mass gain of the model group was lower than that of the normal group， and the NTS high-dose group was close to that of the normal group. Compared with the normal group， the fecal character score of rats in the model group was significantly increased（P<0.05）， and compared with the model group， the scores of the positive drug group and the NTS high-dose group were reduced， but the difference was not statistically significant. HE staining and scanning electron microscopy results showed that NTS could significantly improve ASA-induced small intestinal injury， compared with the normal group， the small bowel injury score of the model group was significantly increased（P<0.01）， compared with the model group， the small bowel injury scores of the NTS low and high dose groups were significantly reduced（P<0.05， P<0.01）. Serum metabolomics screened a total of 75 differential metabolites between the normal group and the model group， of which 55 were up-regulated and 20 were down-regulated， 76 differential metabolites between the model group and the NTS groups， of which 14 were up-regulated and 62 were down-regulated. NTS could modulate three differential metabolites（salicylic acid， 3-hydroxybenzoic acid and 4-hydroxybenzoic acid）， which were involved in 3 metabolic pathways， namely， the bile secretion， the biosynthesis of folic acid， and the biosynthesis of phenylalanine， tyrosine and tryptophan. ConclusionNTS can prevent ASA-induced small bowel injury， and the underlying mechanism may be related to the regulation of bile secretion and amino acid metabolic pathways in rats.

Osteoarthritis (OA) is a chronic degenerative joint disease whose main characteristic is the destruction of articular cartilage, causing pain and disability in patients and seriously affecting their quality of life. OA can be induced by a variety of causes, and pathological changes in articular cartilage are considered to be one of the key driving factors for the occurrence of OA. High mobility group box-1 protein (HMGB1), as a non-histone protein in eukaryotic cells, can participate in regulating the inflammation and apoptosis process of OA chondrocytes, thus leading to the occurrence of OA. This article reviews the research on the mechanism of HMGB1 in OA chondrocytes, with a view to providing new ideas for the clinical prevention and treatment of OA.

Objective To establish the reference interval of serum non-high-density lipoprotein cholesterol(n-HDL-C)in adults in Yan'an city of Shaanxi Province and analyze the influencing factors.Methods A total of 16 921 adults from 10 towns in Yan'an City of Shaanxi Province from January to September 2023 were selected by random sampling.Age,sex,smoking,drinking,exercise,hypertension,diabetes,dyslipidemia,chronic disease,residence,eating habits,marital status,education and monthly income were investigated.Height,weight,waist circumference and blood pressure were measured.Serum triglyceride(TG),total cholesterol(TCHO),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),Apolipoprotein A1(ApoA1),Apolipoprotein B(ApoB)and lipoprotein a[Lp(a)]levels were detected,and n-HDL-C levels were calculated:n-HDL-C(mmol/L)=TCHO(mmol/L)-HDL-C(mmol/L).The 95％reference interval(P25～P97 5)was calculated according to the percentile method recommended in WS/T402-2012 Health Industry Standard of the People's Republic of China.Multivariate logistic regression was used to analyze the influencing factors of serum n-HDL-C level.Results The serum n-HDL-C levels in both males and females were not normally distributed(S=2.119,2.091,all P＜0.001).There were significant differences in serum levels of n-HDL-C among males aged＞60 years old[2.98(2.50,3.37)mmol/L],18～30 years old[2.84(2.49,3.26)mmol/L],31～40 years old[2.98(2.62,3.42)mmol/L],41～50 years old[3.10(2.62,3.47)mmol/L]and 51～60 years old[3.05(2.64,3.46)mmol/L]contrast,and the differences were significant(H=3.618～5.680,all P＜0.05).There were significant differences in serum levels of n-HDL-C among women aged 51～60 years[3.08(2.71,3.44)mmol/L],18～30 years[2.64(2.29,3.07)mmol/L],31～40 years[2.67(2.31,3.08)mmol/L]and 41～50 years old[2.94(2.58,3.29)mmol/L]contrast(H=8.161～13.445,all P＜0.001).There were significant differences in serum n-HDL-C levels among patients aged＞60 years old[2.98(2.57,3.34)mmol/L],18～30 years old,31～40 years old and 41～50 years old contrast,and the differences were significant(H=7.985～14.018,all P＜0.001).The reference interval of serum n-HDL-C level in adult population was obtained by combining the age groups with no statistical significance:males aged 18～60 years old(1.97～3.97mmol/L),＞60 years old(1.86～3.91mmol/L);females aged 18～50 years(1.82～3.74 mmol/L),＞50 years old(1.94～3.88 mmol/L).A total of 16 921 adults were divided into normal n-HDL-C group and abnormal group,and the differences of serum TG(1.02±0.31 mmol/L vs 1.24±0.37mmol/L),TCHO(3.97±1.02 mmol/L vs 4.66±1.25 mmol/L),LDL-C(2.37±0.58mmol/L vs 2.59±0.67 mmol/L)levels and age(43.55±11.52 years vs 46.27±8.13 years)between the two groups were significant(t=2.041～3.151,all P＜0.05),in which the abnormal rate of serum n-HDL-C level was 42.50％.Multivariate Logistic regression analysis showed that males,lack of exercise,overweight or obesity,dyslipidemia,urban residents,and high school education or above were the influential factors for serum n-HDL-C levels in adults in this region(all P＜0.05).Conclusion The reference interval of serum n-HDL-C level in adults in this area was preliminarily established.Males,lack of exercise,overweight or obesity,dyslipidemia,urban residents,and high school education or above were the influential factors of abnormal serum n-HDL-C levels in adults in this area.

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).

ObjectiveThe transcriptome characteristics of different tissues of Codonopsis pilosula were analyzed to illustrate the genetic basis of the accumulation of active ingredients in the root of C. pilosula， and to provide theoretical basis for its high-quality production and cultivation. MethodDifferent tissues of C. pilosula at flowering stage were selected as experimental materials， and the contents of tangshenoside Ⅰ， lobetyolin and atractylenolide Ⅲ were detected by high performance liquid chromatography（HPLC）. RNA-Seq was used to perform transcriptome sequencing of different tissues， and the differentially expressed genes were screened and analyzed by Gene Ontology（GO） and Kyoto Gene and Encyclopedia of Genes and Genomes（KEGG） enrichment analysis， in order to explore the characteristics of active compound distribution and the transcriptional profiles. ResultThe contents of polysaccharides and tangshenoside Ⅰ in the root of C. pilosula were significantly higher than those in other tissues. The transcriptional profiles of the root were significantly different from those of stem， leaf and flower. Cluster analysis， GO and KEGG enrichment analysis of differential gene expression showed that the differential expression genes were mainly enriched in flavonoid and phenylpropanoid biosynthesis， sucrose-starch metabolism， plant hormone signal transduction， plant-pathogen interaction， mitogen-activated protein kinase（MAPK） cascade signal transduction， Adenosine triphosphate（ATP）-binding cassette（ABC） transporter and other pathways. The expression of genes related to biosynthesis of phenylpropanoid compounds were significantly up-regulated in the roots and flowers， and ABC transporter proteins were mostly highly expressed in the flowers. The expression of key enzyme genes for polysaccharide synthesis， such as sucrose：sucrose 1-fructosyltransferase（1-SST） and fructan 1-exohydrolase（1-Feh）， were significantly up-regulated in the roots， and a large number of stress-responsive genes closely related to the accumulation of secondary metabolites were significantly up-regulated in the roots. ConclusionThe active compound content and transcriptional profiles in C. pilosula roots were significantly different from those in stem， leaf， flower and other tissues， showing tissue specificity. Meanwhile， the genes related to stress response and biosynthesis of active compound， such as fructan and phenylpropanoid compounds， were up-regulated in roots of C. pilosula.

Objective:To evaluate the effectiveness and safety of ultrasound-guided percutaneous polidocanol sclerotherapy of the thyroglossal duct cysts in children.Methods:A retrospective analysis of 26 children who were treated with ultrasound-guided percutaneous puncture sclerosis for thyroglossal duct cysts in Beijing Children′s Hospital, Capital Medical University from October 2019 to April 2022, the size of the cyst before treatment was recorded, and the cyst volume in accordance with V(ml) =1/6 πabc cyst volume was calculated. The follow-up time was the 1st, 3rd, 6th, and 12th months after sclerotherapy. And the cyst volume and volume reduction ratio at different time points was calculated. According to changes in the cystic volume, the treatment was considered effective if the cyst volume reduction rate was≥50%. Cosmetic grading scores (CGS) were performed pre-treatment and at the last follow-up after sclerotherapy using the WHO grading system. Complications were recorded during the follow-up period.Results:The cyst volume before treatment was 2.67 (3.78)ml, and the cyst volume at the 1st, 3rd, 6th and 12th month after treatment were 0.66(1.83), 0.45(0.87), 0.40(0.70), 0.38 (0.63)ml, respectively, there were significant differences between pre-treatment and each time point after-treatment (all P<0.001); the volume reduction rate at the last follow-up was (81.48±14.57)%. The reduction rate of cyst volume was more than 50% at the last follow-up in 22 children, the treatment efficiency was 84.62% (22/26). The cosmetic grading scores at the last follow-up after sclerotherapy was 1.74(1.50), and it decreased significantly compared with the pre-treatment score 3.85(0)( P<0.001). There was no skin pigmentation, pain in the injection area, local urticaria and blistering after sclerotherapy, no adverse reactions such as cyst bleeding and drunkenness-like reaction, and no serious complications occurred. There were 2 cases of cysts that presented infection with fever, and no serious complications occurred. Conclusions:Ultrasound-guided percutaneous sclerotherapy is a safe and effective minimally invasive treatment for thyroglossal duct cysts in children.

Objective:To investigate the diagnostic and prognostic value of D-dimer level in patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF).Methods:A total of 142 cases diagnosed with ACLF were randomly selected as research objects in the open cohort using the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF). Plasma D-dimer levels were compared between patients with ACLF and non-ACLF and patients with different ACLF grades. Survival and death group D-dimer levels were compared with the end points of 28 days and 90 days, respectively. The correlation between D-dimer and other laboratory indicators and prognostic scores were investigated. Area under receiver operating characteristic curve (AUROC) was used to evaluate the D-dimer value for predicting the prognosis of ACLF patients. 125 external ACLF cases were used for validation. A Student t test or Mann-Whitney U test was used to compare continuous measurement data between two groups. Kruskal-Wallis test was used to compare continuous measurement data between multiple groups.Results:Plasma D-dimer levels in the ACLF [2 588.5 (1 142.8, 5 472.8) μg/L] ] and non-ACLF group [1 385.5 (612.0, 3 840.3) μg/L] had a significant difference ( P<0.001). ACLF-3 patients had significantly higher D-dimer levels than ACLF-1/2 patients (ACLF-3 vs. ACLF-1, P<0.001; ACLF-3 vs. ACLF-2, P<0.05). Patients who died at 28/90 days had significantly higher D-dimer levels than those whom survived ( P<0.001). There was a significant positive correlation between D-dimer level with prothrombin time (PT), international normalized ratio (INR), high-density lipoprotein C, as well as various prognostic scores (COSSH-ACLFs, CLIF-C ACLFs, CLIF-OFs, MELDs). AUROC of D-dimer in predicting the prognosis of ACLF patients at 28 days and 90 days was 0.751 (95% CI: 0.649-0.852) and 0.787 (95% CI: 0.695-0.878), respectively, which did not differ significantly compared with the predictive ability of other scores ( P<0.05), and similar results were confirmed by an external validation group of 125 cases. Conclusion:D-dimer level is significantly higher in patients with ACLF, so it is an independent predictor of prognosis at 28 and 90 days.

Objective:To explore the progress and prospect of evaluation methods for infertility patients.Methods:From September 2017 to December 2020,199 cases of infertility patients who have accepted mini-hysteroscopy examination in the Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University.The patients who had primary ovary insufficiency,tubal infertility were excluded;patients with hysteroscopy contradiction,such as acute or sub-acute vaginal tract inflammation,en-dometrium lesion or endometrium carcinoma,severe cardiovascular,liver or kidney insufficiency were excluded.40 patients were excluded and 15 patients lost follow up,144 patients were eventually included in the analysis.The patient's age,body mass index,infertility etiology,preoperative and postoperative stimulate ovulation cycle,pregnancy state and pregnancy time were recorded.The effect of mini-hysteroscopy on ovulation induction cycle was analyzed in pregnant patients.Results:The average age of 144 patients was 32.10±4.67 years old.96 (66.67％) patients were found to have intrauterine abnormalities,while 48 (33.33％) patients were found to have normal intrauterine cavity.48 cases of pregnancy,accounting for 33.33％;the median and interquartile ranges[M (Q1,Q3)]of ovulation induction cycles before and after surgery were respectively[3 (0,5)],[2 (1,3)],the difference was statistically significant(P ＜ 0.05).Among the 48 pregnant patients,32 of them had no structural lesions in hysteroscopy,the ovula-tion induction cycle of these patients before and after hysteroscopy were respectively[5 (0,9)],[1 (0,3)],the difference was statistically significant (P ＜ 0.05).Conclusion:Uterine cavity evaluation is important for the assessments of fertility.As an advanced diagnosis instrument,mini-hysteroscopy can not only timely detect the intrauterine abnormalities of patients,but also with great application value in shorten the ovulation cycle in infertility patients and increase the pregnancy rate.