Objective:To investigate the correlation between the promoter methylation level of Dickkopf-related protein 1 (DKK1) gene and diabetic microangiopaopathy complicated with osteoporosis.Methods:Patients with type 2 diabetes mellitus (T2DM) microangiopathopathy who were admitted to our hospital from Jan. 2019 to Dec. 2022 were collected as research objects, and divided into observation group (44 cases) and control group (58 cases) according to whether they were complicated with osteoporosis. Bone mineral density (BMD) of lumbar spine (L1-4) was measured, and bone metabolism indexes, including serum calcium, serum phosphorus, 25-hydroxy vitamin D3[25-hydroxy vitamin D3, 25- (OH) D3], PTH, C-terminal telopeptide of typeI collagen (CTX), procollagen of aminoterminal propeptide (PINP) and tartrate resistant acid phosphatase (TRACP) levels were detected; The promoter methylation level of DKK1 gene was determined.Results:The methylation level of DKK1 gene promoter in the observation group was 5.17%±0.73%, which was significantly higher than that in the control group (3.81%±0.61%), with statistical significance ( t=5.22, P<0.001). The 25- (OH) D3 level, PTH and lumbar bone density in the observation group were significantly lower than those in the control group, while the CTX and TRACP levels were significantly higher than those in the control group ( t was 5.58, 4.35, 4.12, 4.05 and 4.17, respectively, P<0.001). In all patients, the promoter methylation level of DKK1 gene was significantly positively correlated with CTX and TRACP ( r was 0.41 and 0.39, P was 0.006 and 0.027, respectively), and significantly negatively correlated with PTH and lumbar bone density ( r was -0.38 and -0.43, respectively). P=0.015 and 0.003, respectively). ROC curve analysis showed that the area under the curve of DKK1 methylation level to distinguish type 2 diabetes microangionopathy with and without osteoporosis was 0.841 (0.762-0.921), and the sensitivity and specificity were 86.4% and 72.4%, respectively. Conclusion:The methylation level of DKK1 gene promoter is associated with osteoporosis and bone metabolism in T2DM patients with microangiopathia.

ObjectiveTo investigate the material basis of homologous and heterogeneous effect of Aurantii Fructus Immaturus（AFI） and Aurantii Fructus（AF） based on the total statistical moment analysis and molecular connectivity index（MCI）. MethodRelevant literature at home and abroad and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） were consulted to establish the chemical composition database of AFI and AF， and set up their fingerprints by ultra-high performance liquid chromatography（UPLC）， and the total statistical moments and similarity parameters of the fingerprint were calculated. According to MCI， all components of AFI and AF were divided into different component groups， the average values of 0-8^th order（⁰χ-⁸χ） MCI of the common component groups of AFI and AF were calculated. ResultThe values of total zero-order moment（AUC_T） of AFI and AF were （10.57±2.45）×10⁶， （5.09±0.89）×10⁶ μV·s， the values of total first-order moment（MCRT_T） were （11.57±1.58）， （12.10±1.29） min， the values of total second-order moments（VCRT_T） were（24.49±2.30）， （26.49±2.54） min²， respectively. It showed that qualitative and quantitative parameters of AFI and AF were significantly different. The components with high similarity such as neohesperidin， hesperidin and narirutin were screened as the common potential pharmacodynamic components of AFI and AF. The non-common components of AFI， such as alysifolinone and imperatorin， and the non-common components of AF， such as neoeriocitrin and isosakuranin， with high similarity were screened out as potential heterogeneous components of AFI and AF. The composition groups of AFI and AF were classified into six categories， and the similarities between the composition groups of AFI and AF and the total constituents were 0.872-0.979 and 0.918-0.997， the average values of ⁰χ-⁸χ MCI of alkaloids in AFI and AF were 3.65 and 3.14， the average values of ⁰χ-⁸χ MCI of flavonoids were 8.47 and 8.47， the average values of ⁰χ-⁸χ MCI of volatile oils were 2.71 and 3.48， respectively. It showed that there were some differences in MCI of chemical constituents（groups） between AFI and AF. ConclusionThe chemical constituents（groups） of AFI and AF not only differ in content and species， but also in structural characteristics and structure-activity relationship， which can provide a basis for further explaining the scientific connotation of homologous and heterogeneous effect of AFI and AF.

ObjectiveBased on the network pharmacology system and quantitative spectroscopy of traditional Chinese medicine（TCM） compounds， a topological network analysis method with equilibrium constant as the core was established to further explore the interaction between allergenic components and their network targets in Shuanghuanglian injection（SHLI）， in order to provide new ideas and experimental basis for identifying and screening potential allergens of SHLI. MethodAfter one week of adaptive feeding， 72 SPF-grade SD male rats were randomly divided into blank group， SHLI standard group， Lonicerae Japonicae Flos（LJF） group， Scutellariae Radix（SR） group， Forsythiae Fructus（FF） group， and 7 groups of SHLI matching groups（groups 1-7）， with 6 rats in each group. Rats in each group were administered the drug intravenously and blood samples were taken after steady state， high performance liquid chromatography（HPLC） characterization profiles of the testing drugs and plasma components in each group were established， and the peak area changes of the drugs and plasma components in each group were calculated after the component groups were classified. Enzyme-linked immunosorbent assay（ELISA） was used to determine the changes of immunoglobulin E（IgE）， histamine（HIS）， tryptase（TPS）， total complement（CH50） and terminal complement complex（C5b-9） in animal blood samples. MATLAB R2020b v9.9.0 software was used to calculate the network balance constants of the component groups with the targets， and the eigenvalues of the matrices composed of network equilibrium constants were calculated and ranked according to their values. ResultELISA results showed that， compared with the blank group， groups 1-3 could significantly increase the IgE level， groups 1-2， groups 4-6 and SHLI standard group could significantly increase the HIS level， group 4 could significantly increase the CH50 level， groups 1， 3-4， LJF group and FF group could significantly increase the TPS level， SR group could significantly increase the C5b-9 level， and the differences were all statistically significant（P<0.05）. According to the retention time of chromatographic peaks， it was classified into 6 component groups from C1 to C6 by HPLC. The order of the network balance constants of each component group was C6>C4>C1>C5>C3>C2， indicating that C6 had the greatest effect on the allergic reaction， and was most likely to be the allergen. The sequence of eigenvalues was C2>C5b-9>C3>C1>CH50>C6>C5>IgE>TPS>C4>HIS， indicating that component group C2 had the greatest contribution to the whole network. ConclusionBased on the correlation analysis of SHLI component group and allergy-like target network， this study clarified that component group C6 may be a potential allergen in SHLI， and the component group C2 may be a key node in the mechanism of drug action， which can provide new strategies and methods for the screening of allergens in TCM injections.

Objective The characteristics of supramolecular"imprinting template"of volatile oil of Curcuma kwangsiensis and Curcuma phaeocaulis were analyzed and studied based on the supramolecular"qixi"theory of Chinese materia medica combined with chemometrics.Methods The volatile oil of C.kwangsiensis and C.phaeocaulis were extracted by steam distillation,and the fingerprint and composition information of each batch were obtained by GC-MS.Total statistical moment method was used to compare the imprinting characteristics of the"imprinting template"of C.kwangsiensis and C.phaeocaulis.The core index(CI)of each batch of essential oil of C.kwangsiensis and C.phaeocaulis was calculated,and the topological characteristics of types of"imprinting template"of C.kwangsiensis and C.phaeocaulis were compared by chemometrics.Results There was no significant difference in the extraction rate of volatile oil between C.kwangsiensis and C.phaeocaulis.The average values of total zero order moment(AUCT)were(1.907±0.177)×108,(1.979±0.413)×108 μV·s,respectively,showing that there was no significant difference in the total content of volatile oil between the two groups.The mean values of the total first order moment(MCRTT)were(30.969±0.962)and(33.198±0.409)min.The average value of total second order moment(VCRTT)was(56.176±11.368)and(43.891±4.113)min2,respectively,indicating that there were significant differences in the content ratio and species of volatile oils between the two groups.The similarity of total statistical moments of C.kwangsiensis and C.phaeocaulis was mostly lower than the defined value,indicating that the chemical composition and composition ratio of the volatile oil were different.Principal component analysis and orthogonal partial least squares discriminant analysis could obviously divide C.kwangsiensis and C.phaeocaulis into two categories.Through the analysis of P value and VIP value,the CI values of Xvp 4th order,Xvpc 5th order,Xvpc 6th order,Xvpc 7th order,Xvc 3rd order,Xvpc 4th order were the main difference values of C.kwangsiensis and C.phaeocaulis.Conclusion Through the characterization of"imprinting property"and"topological characteristics"of the supramolecular"imprinting template"and combining with chemometric analysis,it is possible to successfully distinguish C.kwangsiensis and C.phaeocaulis,and find the different CI values between two"imprinting templates".

{L-End}Objective To explore the impact of workplace violence (WPV) on occupational burnout among healthcare workers. {L-End}Methods A total of 675 healthcare workers from an infectious disease hospital were selected as the study subjects using typical sampling method. The Workplace Violence in the Healthsector Country Case Studies Research Instruments: Survey Questionnaire and the Maslach Burnout Inventory 2-item were used to investigate the incidence of WPV and occupational burnout. {L-End}Results The incidence of WPV among the study subjects was 35.1%, with incidences of physical and psychological violence at 2.2% and 34.1%, respectively. The detection rates of emotional exhaustion, depersonalization, and occupational burnout were 25.9%, 12.6%, and 52.4%, respectively. The result of multifactorial logistic regression analysis showed that experiencing psychological violence, having a bachelor or master degree or higher, and having more concerns about WPV were influencing factors for emotional exhaustion (all P<0.05). Knowing the reporting process for violent incidents and having more concerns about WPV were influencing factors for depersonalization (all P<0.05). Being in a minority ethnic group, having a bachelor, a master degree or higher, experiencing psychological violence, and having more concerns about WPV were influencing factors for occupational burnout (all P<0.05). {L-End}Conclusion WPV increases the risk of occupational burnout among healthcare workers. Effective measures should be implemented to reduce the incidence of WPV, decrease the level of occupational burnout, and promote the overall well-being of healthcare workers.

Ganjiang (Zingiberis Rhizoma, ZR) and Jiangtan (Carbonized Zingiberis Rhizoma, CZR) have long been used in traditional Chinese medicine (TCM) with a rich history in the treatment of various ailments. While ZR and CZR obviously stem from the same botanical source, their attributes, chemical compositions, pharmacological behaviors, and clinical applications are different owing to variations in the extent of drying and processing they undergo. In this paper, data pertaining to ZR and CZR were retrieved from databases including China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, and Google Scholar. These sources were scrutinized to elucidate the distinctions between ZR and CZR arising from carbonization processing in terms of their ethnopharmacology, quality control, chemical compositions, biological activities, pharmacological mechanisms, and clinical uses. In this study, a total of 56 chemical constituents were identified and isolated from ZR and CZR, which primarily encompassed volatile oils, gingerols, and diphenylheptane compounds. CZR's pharmacological effects include hemostatic, anti-oxidant, analgesic, antibacterial, anti-cancer, and other biological activities. ZR has pungent and warm properties. It is a Yang-supplementing herbal medicine for ailments exacerbated by cold or damp climatic influences. CZR is a product of ZR after undergoing high temperature, with diminished intensity of its pungent and warm attributes. This change leads to a more gradual treatment efficacy, renowned hemostatic effects and its ability to gently invigorate the spleen and effectively alleviate diarrhea. Currently, research on the pharmacological mechanism of CZR is mainly focused on the effects of CZR on coagulation and fibrinolysis. Although the healing effect of CZR has long been known, and some correlation has been found between the changing composition and the changing color of the decoctions, people still lack relatively clear processing mechanisms to reflect the characteristics and specific quality standards of the ingredients of CZR's hemostatic effect. This review provides a systematic summary on quality control, chemical composition, ethnopharmacology, and pharmacology of CZR, offering novel perspectives for advancing the exploration of additional carbonized herbal medicine and fostering their application in clinical settings

OBJECTIVE: To investigate the effects of enhanced recovery after surgery (ERAS) on postoperative function and pain in total hip arthroplasty (THA) patients with high comorbidity. METHODS: Patients with THA who were admitted between January 2020 and January 2022 were selected as the study objects, and a total of 223 patients with high comorbidity met the selection criteria. Patients were randomly divided into two groups using the random envelope method. During perioperative period, 112 cases in the ERAS group were treated according to the ERAS protocol and 111 cases in the control group with the traditional protocol. There was no significant difference in gender, age, body mass index, Charlson comorbidity index, preoperative diagnosis, the type and number of the comorbidities, preoperative visual analogue scale (VAS) score between the two groups ( P>0.05). However, the Harris score of ERAS group was significantly lower than that of control group before operation ( P<0.05). Preoperative and postoperative hospital stays were recorded. The VAS score was used to evaluate the pain before operation, at 1 day after operation, at the leaving bed time, at the day after discharge, and at 2 weeks after operation. Harris score was used to evaluate hip function before operation and at 2 weeks, 1 month, 3 months, 6 months, and 12 months after operation. The incidence of complications, 30-day readmission rate, mortality rate, and patient's satisfaction were recorded. RESULTS: The length of preoperative hospital stay in ERAS group was significantly shorter than that in control group ( P<0.05). But there was no significant difference in the length of postoperative hospital stay between groups ( P>0.05). All patients in the two groups were followed up 12 months. The VAS score in the two groups after operation was lower than that before operation, and showed a gradually trend with the extension of time, with significant differences between different time points ( P<0.05). VAS scores of ERAS group were significantly lower than those of control group at different time points after operation ( P<0.05). The postoperative Harris scores in both groups were higher than those before operation, and showed a gradually increasing trend with the extension of time, with significant differences between different time points ( P<0.05). Harris scores of ERAS group at 2 weeks, 1 month, and 3 months after operation were significantly higher than those of control group ( P<0.05). Complications occurred in 2 cases (1.79%) of the ERAS group and 6 cases (5.41%) of the control group, with no significant difference in incidence ( P>0.05). In the control group, 1 case was readmitted within 30 days after operation, and 1 case died of severe pneumonia within 1 year of follow-up. There was no readmission or death in ERAS group, and there was no significant difference in the above indexes between the two groups ( P>0.05). At last follow-up, the satisfaction rate of patients in ERAS group was slightly higher than that in control group, but the difference was not significant ( P>0.05). CONCLUSION For THA patients with high comorbidity, ERAS protocol can shorten preoperative waiting time, better reduce pain, and improve hip function.
Humans ; Arthroplasty, Replacement, Hip ; Enhanced Recovery After Surgery ; Comorbidity ; Pain ; Postoperative Period

【Objective】 To reveal the integral in vivo polypharmacokinetics (PPK) similarity or difference between Jinyinhua (Lonicerae Japonicae Flos, LJF) and Shanyinhua (Lonicerae Flos, LF), and provide reference for their clinical application. 【Methods】 The PPK model and its total quantum statistical moment similarity (TQSMS) method were used to compare the integral PPK profiles of nine components with anti-inflammatory efficacy (rutin, caffeic acid, chlorogenic acid, cryptochlorogenic acid, dispsacoside B, macranthoidin B, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C) of LJF and LF. A total of 54 Specific Pathogen Free (SPF) grade Kunming (KM) mice were randomized into LJF group and LF group (n = 27), and each group was divided into nine subgroups (n = 3) according to different time points. Subsequently, mice model of p-xylene-induced ear edema was constructed by oral administration of LJF and LF. The concentrations of the nine anti-inflammatory components in plasma samples of the mice were determined by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). And the pharmacokinetics (PK) parameters of single component and the integral PPK parameters [total quantum statistical moment (TQSM) and TQSMS] of multiple components were calculated by Drug And Statistics (DAS) software and home-brew programs with Excel, respectively. 【Results】 There were significant differences in single-component PK parameters between LJF and LF (P < 0.05). Whereas, no significant differences were found in multi-component TQSM parameters, including total quantum zero moment (AUCT0-t, AUCT0-∞) and total quantum first moment (MRTT0-t, MRTT0-∞) for the total quanta (P > 0.05). Accordingly, single-component TQSMS varied from 0.220 4 to 0.968 9, and that for the total quanta was 0.828 4, suggesting no significant differences in the speed and extent of bioavailability between LJF and LF. Furthermore, in light of high TQSMS (0.828 4), the integral PPK profiles of the nine anti-inflammatory components of LJF and LF were similar under 90% confidence intervals. 【Conclusion】 The PPK model and its TQSMS method are appropriate and efficient to compare the similarity or difference of integral PPK profiles of multi-component herbal medicines. It is suggested in this research that LJF can be replaced with LF or vice versa for anti-inflammatory treatment.

Objective:To establish the clinical laboratory genetic diagnosis procedures for Marfan syndrome (MFS) and carry out clinical laboratory genetic diagnosis for MFS families.Methods:The second generation high-throughput sequencing was used to sequence and analyze the FBN1 gene of two MFS families who visited to Fuwai Central China Cardiovascular Hospital (Heart Center of Henan People′s Hospital) from January to December 2020, and then Sanger sequencing was used to verify the second generation high-throughput sequencing results. At the same time, the sanger sequencing of mutation sites was performed on normal family members and 100 healthy people to identify the pathogenic mutations of FBN1 gene in the MFS families. The pregnant women of two families were guided for prenatal diagnosis in the second trimester of pregnancy.Results:The clinical laboratory diagnosis of MFS showed that two MFS patients had the pathogenic mutation of c.2560T>C heterozygous mutation and c.6772T>C heterozygous mutation in FBN1 gene, respectively. The mutation was not observed in 100 healthy people and normal members in two families. The prenatal diagnosis showed that there was a heterozygous mutation of FBN1 gene c.2560T>C in the first fetus of the MFS family, which was MFS. There was no mutation in the FBN1 gene in the second fetus of the MFS family, so it was recommended to continue the pregnancy. The results of postpartum follow-up were consistent with the results of clinical laboratory diagnosis.Conclusion:The clinical laboratory genetic diagnosis procedures for MFS have been established successfully, which provides an important reference for clarifying the clinical diagnosis of MFS.

ObjectiveBased on the supramolecular "imprinting template" theory， the autonomous action law of the component groups of Shentong Zhuyutang in the preparation process of medicinal materials-decoction pieces-formulas was studied to clarify the quantitative transfer law of its quality attributes. MethodUltra performance liquid chromatography（UPLC） fingerprint of Shentong Zhuyutang was established with mobile phase of 0.4% phosphoric acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-2.5 min， 100%A； 2.5-6 min， 100%-96%A； 6-15 min， 96%-92%A； 15-25 min， 92%-88%A； 25-35 min， 88%-75%A； 35-50 min， 75%-65%A； 50-60 min， 65%-50%A； 60-65 min， 50%-30%A； 65-70 min， 100%A） and detection wavelength of 235 nm， and the total statistical moments， information entropy and primary feeding amount of fingerprint of medicinal materials， decoction pieces and benchmark samples were calculated. Dry extract rate of the benchmark samples， the transfer rates and the addition parameters of medicinal materials-decoction pieces-formulas were calculated. ResultSimilarities of the total statistical moments of UPLC fingerprint of 15 batches of medicinal materials and decoction pieces were>0.89， the relative standard deviations（RSDs） of information entropy of UPLC fingerprint of 12 medicinal materials and decoction pieces were<10%. RSDs of total first-order moment（MCRT_T） and information entropy of Shentong Zhuyutang（medicinal materials） were 5.5% and 2.3%， while the RSDs of MCRT_T and information entropy of Shentong Zhuyutang（decoction pieces） were 4.8% and 2.6%， respectively. The dry extract rate of 45 batches of Shentong Zhuyutang was 17.2%-20.2%. The transfer rate of medicinal materials to decoction pieces was within the range of data fluctuation， which was 70%-130% of the average value. The overall transfer rates of medicinal materials to decoction pieces and decoction pieces to benchmark samples were 101.8% and 83.0%， respectively. ConclusionThe quality properties of Shentong Zhuyutang benchmark samples can be studied by total statistical moment analysis and primary feeding amount analysis， which can confirm the supramolecular "imprinting template" theory to a certain extent.