Hungary, as the first European country to legislate TCM, its legislation experience has significant implications for the international development of TCM. This article reviewed the historical process of TCM legislation in Hungary, summarized its legislative achievements, and analyzed the problems encountered during the implementation process. It was found that the current challenges faced by TCM legislation in Hungary mainly include constraints from the dominance of modern medicine, restrictions from strict qualification requirements, insufficient public awareness, difficulties in TCM registration, and challenges in policy coordination and cooperation. Based on these findings, the article proposed countermeasures such as improving the legal framework, strengthening educational cooperation, enhancing public awareness, promoting the mutual recognition of standards between China and Europe, and deepening China-Hungary collaboration. These measures aim to further improve the legislation and implementation of TCM in Hungary, thereby promoting the healthy development of TCM in Hungary and the global service trade of TCM.

Objective:To explore the key copy number variation (CNV) regions, abortion candidate genes and signaling pathways associated with recurrent spontaneous abortion (RSA).Methods:A retrospective cohort study was conducted based on the data of 1 870 miscarriage cases of RSA patients who received CNV analysis by high-throughput sequencing technology in the Laboratory Medicine Department of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2022. These cases were divided into different groups based on the age of miscarriage and gestational age of the pregnant women. Chi-square test or Fisher's exact test was used to analyze the distribution of chromosome abnormalities and CNV. Gene functions and signaling pathways in RSA-related CNV were identified by gene enrichment analysis.Results:Among the 1 870 tissues, 1 001 (53.53%) cases were detected with chromosomal abnormalities. A total of 140 CNVs were detected in 93 tissues (9.29%), including 34 submicroscopic CNVs (segment<10 Mb) and 106 large CNVs with segment≥10 Mb. Submicroscopic pathogenicity CNVs with statistical differences were involved 1p36.33p36.23, 2q37.3, 4p16.3, 22q11.21 (χ 2=6.99, P=0.008) in early RSA embryos (≤12 weeks). 16p11.2 and Xp11.23p11.22 microdeletion were firstly reported in abortion cases. Significantly recurrent large CNVs were mainly involved 18q22q23 (del/dup), 4p16p15, 9p24p22, 8p23p22, and Xp22.3 regions, and the candidate genes mainly concentrated on PI3K-Akt and JAK-STAT signaling pathway. Conclusion:Rare submicroscopic CNVs and recurrent large CNVs were associated with RSA in early pregnancy. GO and KEGG database analysis revealed potential abortion candidate genes and signaling pathways, providing new information for the genetic etiology of RSA.

Objective:To explore the key copy number variation (CNV) regions, abortion candidate genes and signaling pathways associated with recurrent spontaneous abortion (RSA).Methods:A retrospective cohort study was conducted based on the data of 1 870 miscarriage cases of RSA patients who received CNV analysis by high-throughput sequencing technology in the Laboratory Medicine Department of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2022. These cases were divided into different groups based on the age of miscarriage and gestational age of the pregnant women. Chi-square test or Fisher's exact test was used to analyze the distribution of chromosome abnormalities and CNV. Gene functions and signaling pathways in RSA-related CNV were identified by gene enrichment analysis.Results:Among the 1 870 tissues, 1 001 (53.53%) cases were detected with chromosomal abnormalities. A total of 140 CNVs were detected in 93 tissues (9.29%), including 34 submicroscopic CNVs (segment<10 Mb) and 106 large CNVs with segment≥10 Mb. Submicroscopic pathogenicity CNVs with statistical differences were involved 1p36.33p36.23, 2q37.3, 4p16.3, 22q11.21 (χ 2=6.99, P=0.008) in early RSA embryos (≤12 weeks). 16p11.2 and Xp11.23p11.22 microdeletion were firstly reported in abortion cases. Significantly recurrent large CNVs were mainly involved 18q22q23 (del/dup), 4p16p15, 9p24p22, 8p23p22, and Xp22.3 regions, and the candidate genes mainly concentrated on PI3K-Akt and JAK-STAT signaling pathway. Conclusion:Rare submicroscopic CNVs and recurrent large CNVs were associated with RSA in early pregnancy. GO and KEGG database analysis revealed potential abortion candidate genes and signaling pathways, providing new information for the genetic etiology of RSA.

In order to standardize the quality control of traditional Chinese medicine（TCM） dispensing granules， the Chinese Pharmacopoeia Commission has promulgated and implemented 200 national drug standards for TCM dispensing granules， but there are still varieties of TCM dispensing granules without unified standards. Many provinces have actively invested in the formulation of provincial standards for TCM dispensing granules to make up for the gaps in standards for varieties of traditional Chinese medicine dispensing granules other than the national standards. By the end of July 2022， 29 provincial-level administrative regions have successively promulgated and implemented a total of 5 602 provincial standards for TCM dispensing granules， involving more than 400 varieties. In order to better understand the formulation and characteristics of provincial standards， this study took 105 provincial standards that have been promulgated and implemented in Henan province as an example， and comprehensively analyzed the formulation and characteristics through quality control indicators such as dry extract rate of raw materials， contents of index components and their transfer rates， specifications and so on. The formulation and characteristics of the same TCM dispensing granules in the provincial standards of different provinces were further analyzed， in order to provide reference for the formulation of provincial standards of TCM dispensing granules and the implementation of national standards.

OBJECTIVE： To optimize the extraction technology of verbascoside from Cistanche tubulosa， and to provide reference for further development and comprehensive utilization of C. tubulosa. METHODS： The content of verbascoside in C. tubulosa was determined by HPLC. The determination was performed on  Inertsil-ODS-3V  column with  mobile phase consisted of methanol-0.2％ formic acid aqueous solution （40 ∶ 60， V/V） at  the flow rate  of  1 mL/min. The column temperature was 30 ℃， the detection wavelength was 330 nm， and the sample size  was 10 μL. Using extraction rate of verbascoside as index， soaking time， ethanol concentration， liquid-solid ratio， extraction time and extraction times were investigated by single factor tests. According to the results of above tests， ethanol concentration， liquid-solid ratio and extraction time were optimized by Box-Behnken response surface methodology. The verification tests were carried out on the optimized extraction technology. RESULTS： The linear range of verbascoside was 18.65-932.4 μg/mL. The optimal extraction technology included that ethanol concentration 63％， liquid-solid ratio 8 ∶ 1 （mL/g）， soaking for 2 h， extraction time 1.5 h， extracting for 2 times. The extraction rates of verbascoside in the three parallel verification tests were 78.21％， 76.95％， 79.34％， respectively. The relative errors of those to predicted value 76.76％ were 1.89％， 0.25％， 3.36％. CONCLUSIONS： The optimized extraction technology of verbascoside from C. tubulosa is stable and feasible， and is suitable for the extraction of verbascoside.

OBJECTIVE: To compare the differences in the clinical therapeutic effects on perimenopausal syndrome (PMS) between the combined treatment with the transcutaneous electrostimulation at Shuitu (ST 10) and the seed-pressure therapy at the auricular points and the hormone replacement therapy. METHODS: A total of 64 PMS patients were divided into an observation group (30 cases) and a control group (34 cases) according to patient's willingness. In the observation group, the transcutaneous electrostimulation at Shuitu (ST 10) was combined with the seed-pressure therapy at the auricular points. The stimulation intensity at Shuitu (ST 10) was ranged from 15 to 20 mA, for 20 min in each treatment, twice a week. The 8 treatments made one course and 3 courses were required. Additionally, the seed-pressure therapy was used at neifenmi (CO), Shenmen (TF), luanchao, zigong, gan (CO), shen (CO), once a week, retained for 5 days. The 4-week treatment was as one course and a total of 3 courses were required. In the control group, the hormone replacement therapy was applied. On Day 5 of menstruation, progynova was prescribed for oral administration, 1 mg, once a day, continuously for 21 days. On Day 12 in the oral administration of progynova, dydrogesterone was used, 20 mg, once every day, continuously for 10 days. Totally, 3 courses were required. Separately, before treatment and in 1 and 3 months after treatment, Kuppermann score, the sexual hormone levels [follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E)] and the adverse reactions were observed in the patients of the two groups. RESULTS: In 1 and 3 months after treatment, Kuppermann scores were reduced significantly as compared with those before treatment in the two groups (all <0.05). The levels of serum FSH and LH were reduced remarkably as compared with those before treatment in the two groups (all <0.05) and the level of serum E was increased remarkably as compared with that before treatment in the two groups (all <0.05). After treatment, the differences in the above indexes were not significant between the two groups (all >0.05). In the control group, the incidences of the adverse reactions such as vaginal bleeding, bread distending pain and endometrial thickening were higher than those in the observation group [17.6% (6/34) vs 0% (0/30), 20.6% (7/34) vs 3.3% (1/30), 8.8% (3/34) vs 0% (0/30), all <0.05]. CONCLUSION The combined treatment with the transcutaneous electrostimulation at Shuitu (ST 10) and the seed-pressure therapy at the auricular points achieves the similar therapeutic effects on PMS as compared with the hormone replacement therapy. This combined therapy effectively relieves the clinical symptoms and improves the sexual hormone levels. The adverse reactions and the complications are less obviously as compared with the hormone replacement therapy.
Acupuncture Points ; Acupuncture, Ear ; Female ; Follicle Stimulating Hormone ; Humans ; Luteinizing Hormone ; Perimenopause

Objective: To analyze the correlation between circumcision and incidence and clearance of male genital HPV infection. Methods: From May to July 2014, 18-55 year old men who had sexual behavior history were recruited from the general population in Liuzhou, Guangxi to set up a cohort. Totally, 113 circumcised and 560 uncircumcised men were enrolled and interviewed using a questionnaire (including information on demographic characteristics and sexual behaviors), then they were followed-up with 6-month interval for 2 times. On each visit, specimens of male external genitalia were collected and genotyped for HPV DNA. The differences of incidence and clearance of genital HPV infections between circumcised and uncircumcised men were analyzed by Log-rank test. Cox regression was used to analyze the relationship between circumcision and incidence and clearance of HPV infection. Results: The median age (P₂₅, P₇₅) of circumcised and uncircumcised men were 28 (24, 35) and 32 (24, 31), respectively. The incidences of any HPV infections were 9.1 (95%CI: 2.4-15.7) and 8.4 (95% CI: 5.6-11.2) per 1 000 person-months (χ²=0.10, P=0.758), respectively. The clearance of circumcised men [136.3 (95%CI: 70.0-202.7) per 1 000 person-months] was higher than that in uncircumcised men [89.6 (95%CI: 65.9-113.3) per 1 000 person-months] (χ²=8.19, P=0.004). In multivariate COX regression analysis, compared with uncircumcised men, circumcised men had higher possibility to clear any HPV infections (HR: 2.41, 95%CI: 1.30-4.46). Compared with men having one sexual partner, people having more than 4 sexual partners had lower possibility to clear any HPV infections (HR: 0.49, 95%CI: 0.25-0.96). Compared with 18-25 years old men, men aged 26-35 years old had higher possibility to clear high-risk HPV infections (HR: 2.14, 95%CI: 1.08-4.23). Conclusion Circumcised and uncircumcised men had similar incidence of genital HPV infection, whereas, men conducted circumcision and having fewer sexual partners could increase the clearance of genital HPV infections.

Objective To explore the effect of different concentrations of endothelin-1 (ET-1)on the en-dogenous nitric oxide (NO)and hydrogen sulfide (H2S)pathways of vascular smooth muscle cells (A7r5 cell lines)in rats.Methods A7r5 cell lines were divided into the control group and the experimental group.ET-1 at a concentra-tion of 10 -8-10 -6 mol/L was added into the experimental group,and as for the control group,the same volume of sterile phosphate buffered saline (PBS)buffer solution was added.The content of NO and H2S in A7r5 cell lines was detected by fluorescent NO probe and H2S probe after ET-1 stimulation for 48 h,respectively.The content of NO in the supernatant was measured by NO assay kit at 48 h of the incubation.The content of H2S in the supernatant was measured by polarographic H2S sensor at 48 h of the incubation. The expressions of inducible nitric oxide synthase (NOS2),endothelial nitric oxide synthase (NOS3),cystathionine -γ -lyase (CSE),cystathionine -β -synthase (CBS)and proliferating cell nuclear antigen (PCNA)were detected by the Western blot method.Results The rela-tive fluorescence intensity of the content of NO in the A7r5 cell lines of ET-1 10 -8,10 -7 and 10 -6mol/L groups (0. 078 ± 0. 080,0.075 ± 0.002,0.056 ± 0.009)was markedly lower than that in the control group(0.094 ± 0. 061), and the differences were statistically significant(F＝15.248,P＜0.05);Compared with the control group[(2. 131 ± 0. 484)μmol/L],the content of NO in the supernatant of the experimental groups [(1.391 ± 0.134 )μmol/L, (1.219 ± 0. 280)μmol/L,(1.116 ± 0.181)μmol/L]was significantly decreased,and the differences were statistically significant(F＝20.833,P＜0.01);NOS2 protein expression(0.457 ± 0.097,0.462 ± 0.116,0.438 ± 0.180)was decreased markedly compared with that of the control group(0.721 ± 0.222),and the differences were statistically sig-nificant(F＝6.196,P＜0.01),but the expression of NOS3 showed no significant differences(F＝2.669,P＞0.05). The relative fluorescence intensity of the content of H2S in the A7r5 cell lines of ET-1 10 -8,10 -7 and 10 -6mol/L groups (0.063 ± 0.002,0.056 ± 0.008,0.042 ± 0.009)was markedly lower than that in the control group (0.082 ± 0. 006),and the differences were statistically significant(F ＝16.297,P＜0.01);Compared with the control group [(29.439 ±4.236)μmol/L],the content of H2S in the supernatant of the experimental groups [(17.516 ±5.144) μmol/L,(14.481 ± 4.885)μmol/L]was significantly decreased,and the differences were statistically significant (F＝12.518,P ＜0.01).CBS protein expression(0.359 ± 0.096,0.270 ± 0.038,0.174 ± 0.051)was decreased markedly compared with that of the control group(0.707 ± 0.107),and the differences were statistically significant (F＝20.833,P＜0.01),and the expression of CSE showed no significant differences(F＝0.708,P＞0.05).The data showed that PCNA protein expression in the 10 -7mol/L ET-1 group(0.686 ± 0.180)significantly increased com-pared with that of the control group(0.437 ± 0.191),and the difference was statistically significant (t＝ -2.840,P＜0.01).Conclusion ET-1 stimulation can lead to the proliferation of vascular smooth muscle cells and down-regu-late its endogenous NO and H2S pathways.

Objective To investigate the association of red cell distribution width (RDW) with prognosis in patients with sepsis. Methods Patients with sepsis admitted to intensive care unit (ICU) of the First Hospital of Soochow University from January 2011 to December 2016 were enrolled. All clinical data were collected for participants, which mainly included basic data, main underlying disease, site of infection, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ ) score, blood routine test, biochemical test, blood gas analysis, coagulation index, procalcitonin (PCT), hospitalization days, and 28-day and 90-day mortality. Patients were divided into two groups according to whether the RDW levels were higher than the time of admission or not. Kaplan-Meier survival curve was performed to analyze 28-day and 90-day cumulative survival rates in two groups. Multivariate Cox regression analysis was done to find the independent risk factors of death in patients with sepsis. Results 196 septic patients were eligible to participate into this study. 150 patients (53.57%) had higher RDW levels than those at the time of admission. Compared to negative or static change of RDW group, positive change of RDW group had higher APACHE Ⅱ score (20.42±6.29 vs. 16.17±6.37), more percentage of chronic kidney insufficiency (35.24% vs. 19.78%), bloodstream infection (32.38% vs. 15.38%), continuous renal replacement therapy (CRRT: 32.38% vs. 16.48%), higher level of C-reactive protein [CRP (mg/L): 14.71±3.52 vs. 11.15±7.94], and higher serum creatinine [SCr (μmol/L): 128.0 (74.0, 263.5) vs. 90.0 (57.0, 145.5)], PCT [μg/L: 3.45 (2.39, 6.64) vs. 2.35 (0.56, 3.54)], and lactic acid [Lac (mmol/L): 3.40±1.72 vs. 2.70±1.61]; and had lower levels of hematocrit (Hct: 0.357±0.128 vs. 0.437±0.143), hemoglobin [Hb (g/L):103.60±22.63 vs. 115.67±28.49], platelets [PLT (×109/L): 133.37±87.29 vs. 191.43±87.65], albumin [Alb (g/L):28.15±5.72 vs. 35.51±5.91], total cholesterol [TC (mmol/L): 2.43±1.12 vs. 3.05±1.55], estimated glomerular filtration rate [eGFR (mL·min-1·1.73 m-2): 82.02±63.90 vs. 125.46±83.47], and oxygenation index [PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 229.69±60.61 vs. 264.21±74.78]; and longer time of hospitalization [days: 17.0 (12.0, 21.7) vs. 11.0 (7.0, 18.0)], higher 28-day and 90-day mortality (57.14% vs. 36.26%, 62.86% vs. 47.25%) with statistically significant differences (all P < 0.05). It was shown by Kaplan-Meier survival curve that the 28-day and 90-day cumulative survival rate in positive change of RDW group was significantly lower than that of negative or static change of RDW group (χ 12 = 8.462, χ22 = 6.411, both P < 0.05). It was shown by multivariate Cox regression that high APACHE Ⅱ score [odds ratio (OR) = 1.049, 95% confidence interval (95%CI) = 1.010-1.090, P = 0.013] and positive change of RDW (OR = 0.517, 95%CI = 0.280-0.953, P = 0.034) were the risk factors of death in patients with sepsis. Conclusions The change of RDW values during hospitalization was related to the poor outcomes in patients with sepsis. The increase of RDW predicts the progress of sepsis and bad prognosis. Serial surveillance of RDW values could provide useful information for long-term prognosis in sepsis.

OBJECTIVE:To explore the role of clinical pharmacists in therapy for patient with interstitial lung disease (ILD) induced by erlotinib. METHODS:Clinical pharmacists participated in the therapy for ILD in a patient receiving erlotinib target treat-ment after thoracic vertebra and lumbar radiation,analyzed the cause of ILD and suggested to stop taking imipenem and cilastatin sodium,fluconazol and erlotinib according to lab indexes and patient’s symptom;took prednisone 30 mg,po,qd,for anti-inflam-mation instead of methylprednisolone;adjusted the dose of prednisone to 40 mg/d,and additionally took Carbocisteine oral solution 10 ml,tid,for improving respiratory symptom;panipenem betamipron 1 g,ivgtt,bid,instead of piperacillin sodium and sulbactam sodium. RESULTS:Physicians adopted the suggestions of clinical pharmacists,and the symptom of anhelation and double pneumo-nia recovered;discharged medication plan was erlotinib 150 mg,po,qd. CONCLUSIONS:The patient with radiation history easily suffers from ILD when using erlotinib,and should use erlotinib carefully in the clinic. Clinical pharmacists participated in drug ther-apy and promote safe and rational use of drugs in the clinic.