BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To observe the clinical efficacy of treating somatoform pain disorder(SPD)with electroacupuncture(EA)at the Governor and Conception Vessel points plus duloxetine.Methods:Eighty-two SPD patients were randomly allocated to an observation group and a control group,with 41 cases in each group.The control group was intervened by oral administration of duloxetine hydrochloride enteric capsules at a dose of 60 mg per time once a day;based on the medication,the observation group received additional EA treatment by selecting points from the Governor and Conception Vessels.Clinical efficacy was evaluated after 8 weeks of treatments;changes in the scores of the short-form McGill pain questionnaire(SF-MPQ),self-report symptom inventory,symptom check list-90(SCL-90),Pittsburgh sleep quality index(PSQI),and generic quality of life inventory-74(GQOLI-74)were also compared.Results:After the intervention,the observation group surpassed the control group in comparing the total effective rate(P＜0.05).The SF-MPQ score,SCL-90 somatization score,and PSQI score dropped notably in both groups after treatment,and the intra-group differences were statistically significant(P＜0.05);the three scores were significantly lower in the observation group than in the control group(P＜0.05).The GQOLI-74 score got an increase in each dimension in both groups after treatment,and the intra-group differences were also statistically significant(P＜0.05);the GQOLI-74 dimension scores were all significantly higher in the observation group than in the control group(P＜0.05).Conclusion:For patients with SPD,combining EA at the Governor and Conception Vessel points and duloxetine hydrochloride enteric capsules can markedly improve their clinical symptoms and quality of life.

OBJECTIVE: Functional constipation (FC) is a common intestinal disease worldwide. Despite the presence of criteria such as Roman IV, there is no standardized diagnosis and treatment algorithm in Hong Kong that combines both Western and Chinese medicine approaches. This study integrates current effective and safe diagnosis and treatment methods for FC and provides a clear and scientific pathway for clinical professionals and patients. METHODS: A systematic search of the PubMed, Cochrane Library, and China National Knowledge Infrastructure databases was performed from their inception to June 30th, 2022, collecting the current evidence about the efficacious integrative management for FC. We organized a meeting of professionals in fields relevant to treatment and management of FC to develop a consensus agreement on clinical pathway process. RESULTS: We developed a clinical pathway for the treatment of FC based on the most recent published guidelines and consultation with experts. This pathway includes a hierarchy of recommendations for every step of the clinical process, including clinical intake, diagnostic examination, recommended labs, diagnostic flowchart, and guidance for selection of therapeutic drugs. CONCLUSION This pathway establishes clinical standards for the diagnosis and treatment of FC using Chinese medicine and Western medicine; it will help to provide high-quality medical services in Hong Kong for patients with FC. Please cite this article as: Wei DJ, Li HJ, Lyu ZP, Lyu AP, Bian ZX, Zhong LL. A clinical pathway for integrative medicine in the treatment of functional constipation in Hong Kong, China. J Integr Med. 2023; 21(6): 550-560.
Humans ; Hong Kong ; Integrative Medicine ; Critical Pathways ; China ; Constipation/therapy*

OBJECTIVE: To study the clinical features of very preterm infants with prelabor rupture of membranes (PROM) and predictive factors for early-onset sepsis (EOS) and death. METHODS: A retrospective analysis was performed for the clinical data of the very preterm infants with PROM (with a gestational age of < 32 weeks) who were admitted to the neonatal intensive care unit from January 2018 to May 2020. According to the time from membrane rupture to delivery, the infants were divided into four groups: < 18 hours ( RESULTS: There was no significant difference in the incidence rates of major neonatal complications and mortality rate among the very preterm infants with different times of PROM ( CONCLUSIONS Prolonged PROM does not increase the incidence of neonatal complications and mortality in very preterm infants. Adverse outcomes of very preterm infants with PROM are mainly associated with lower birth weights, lung immaturity, and systemic infection.
Female ; Fetal Membranes, Premature Rupture ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; Infant, Very Low Birth Weight ; Pregnancy ; Retrospective Studies

Objective: By observing the effects of electroacupuncture (EA) on the apoptosis of conjunctival cells of rabbits with dry eye syndrome (DES) and the expressions of apoptosis-related proteins Caspase-3, Fas and Bcl-2, to discuss the mechanism of EA in the treatment of DES from the perspective of cell apoptosis. Methods: Male New Zealand rabbits were randomly divided into a normal group (NG), a model group (MG), an EA group (EAG) and a sham EA group (SEAG). DES rabbit model was developed by eye drop of 0.1％ benzalkonium chloride. The rabbit tear secretion and tear film break-up time (BUT) were measured; terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling (TUNEL) assay was used to detect the apoptosis of conjunctival cells; the expressions of Caspase-3, Fas and Bcl-2 proteins in conjunctival cells were detected by immunohistochemistry. Results: Compared with the NG, the rabbit tear secretion decreased and the BUT was shortened in the MG (both P<0.01); compared with the MG and the SEAG, the rabbit tear secretion increased and the BUT was prolonged in the EAG (all P<0.05). Compared with the NG, the apoptosis of rabbit conjunctival cells increased (P<0.01), the expressions of Caspase-3 and Fas proteins increased (both P<0.05), and the expression of Bcl-2 protein decreased (P<0.01) in the MG; compared with the MG and the SEAG, the apoptosis of rabbit conjunctival cells decreased (both P<0.01), the expressions of Caspase-3 and Fas proteins decreased (all P<0.05), and the expression of Bcl-2 protein increased (both P<0.01) in the EAG. Conclusion: EA can inhibit the apoptosis of rabbit conjunctival cells, down-regulate the expressions of apoptosis-related proteins Caspase-3 and Fas, and up-regulate the expression of Bcl-2 protein, which may be one of the mechanisms of EA in treatment of DES.

OBJECTIVE: To explore the screening value of osteoporosis self-assessment tool for Asians (OSTA) and the optimal cut-off value in Chinese healthy physical examination population. METHODS: We selected a healthy physical examination population for bone mineral density screening at the Health Examination Center in Peking University Third Hospital from 2013 to 2016. Quantitative ultrasound (QUS) results were used as the gold standard, and T value ≤-2.5 was defined as osteoporosis patients. Diagnostic test methods were used to analyze the sensitivity, specificity, likelihood ratio and area under curve (AUC) of different cut points of OSTA. The screening accuracy of OSTA at different cut points was compared and the optimal cut-point value determined. RESULTS: A total of 5 833 subjects were included in the study, with an average age of (48.3±17.5) years and 2 594 women (44.5%). The QUS test showed 403 patients with osteoporosis (6.9% of the total population), 343 female osteoporosis patients (13.22% of the female population). In the whole age group, AUC at the international routine cut-off value (OSTA ≤-1) screening for osteoporosis was 0.815 (95%CI: 0.804-0.825), and screening accuracy was higher in the women (AUC=0.837, 95%CI: 0.823-0.851) than that in the men (AUC=0.767, 95%CI: 0.752-0.781; P<0.05). In the whole age group, when the optimal cut-off value was 0, its AUC 0.842 (95%CI: 0.832-0.851) was significantly higher than that when the cut-off value was -1 (P<0.01), and net reclassification improvement (NRI) increased by 5.5%. In the 40 to 65-year-old group, when OSTA cut-off value ≤0, the screening accuracy was significantly higher (NRI=19.5%, P=0.003) than that when it was -1. CONCLUSION The OSTA screening tool had good osteoporosis screening value in healthy people, and the screening accuracy in women is higher than that in men. Increasing the screening cut-off value of OSTA would be helpful to improve the screening accuracy in the whole and 40 to 65-year-old population. There may be different optimal cut-off values for different age group population.
Absorptiometry, Photon ; Adult ; Aged ; Asians ; Bone Density ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis ; Physical Examination ; Risk Assessment ; Self-Assessment ; Sensitivity and Specificity

OBJECTIVETo compare the safety of sevoflurane anesthesia with laryngeal mask and tracheal intubation in cesarean section in women with heart disease.

METHODSFifty-two pregnant women with heart diseases undergoing cesarean section were randomized into laryngeal mask (LAM) group and tracheal intubation group. In LAM group, 6% sevoflurane was given at the rate of 6 L/min for induction with a maintenance sevoflurane concentration of 3%. In the intubation group, 1.5 mg/kg propofol and 1 µg/kg remifentanil were injected intravenously, and after achieving D0 with Narcotrend monitoring, 0.9 mg/kg rocuronium was injected and intubation was performed 1 min later. The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were recorded in the two groups before anesthesia induction (T), at intubation or laryngeal mask placement (T), skin incision (T), and extubation or laryngeal mask removal (T). The surgery to fetal birth time, uterine incision to fetal childbirth time, drug discontinuation to awake time, and newborn Apgar scores were also recorded. Sevoflurane consumption and maternal comfort during hospitalization were compared between the two groups.

RESULTSIn LAM group, HR and MBP at Tand Twere significantly lower than those in the intubation group (P<0.05). The drug discontinuation to extubation time and to awaken time were significantly shorter in LAM group than in the intubation group (P<0.05), but the operation time and fetal child birth time were comparable between the two groups (P>0.05). The women in LAM group reported better physical and psychological comforts than those in the intubation group (P<0.05). The neonatal Apgar scores and the scores of health education, satisfaction with hospital environment and service were all similar between the two groups (P>0.05).

CONCLUSIONSevoflurane anesthesia with laryngeal mask can achieve satisfactory anesthetic effects in cesarean section in women with heart disease.

Background: MicroRNAs (miRNAs) are key regulators during tumor initiation and progression. MicroRNA-375 (MiR-375) has been proven to play a tumor-suppressive role in various types of human malignancies; however, its biological role in clear cell renal cell carcinoma (ccRCC) remains unclear. The purpose of this study was to explore the biologic role as well as the underlying mechanism of miR-375 in ccRCC progression. Methods: Quantitative polymerase chain reaction (qPCR) was applied to test the expression of miR-375 in tissues and cell lines by t-test. Functional experiments were used to investigate the biological role of miR-375 utilizing a gain-of-function strategy. The target of miR-375 was investigated by bioinformatic analysis and further verified by luciferase reporter assay, qPCR, Western blotting, and functional experiments in vitro. Results: Our study demonstrated that miR-375 was significantly downregulated in ccRCC tissues (cancer vs. normal, 0.804 ± 0.079 vs. 1.784 ± 0.200, t = 5.531 P < 0.0001) and cell lines, and loss of miR-375 expression significantly associated with advanced Fuhrman nuclear grades (Grade III and IV vs. Grade I and II, 1.000 ± 0.099 vs. 1.731 ± 0.189, t = 3.262 P = 0.003). Functional studies demonstrated that miR-375 suppressed ccRCC cell proliferation, migration, and invasion (all P < 0.05 in both 786-O and A498 cell lines). Multiple miRNA target prediction algorithms indicated the well-studied oncogene YWHAZ as a direct target of miR-375, which was further confirmed by the luciferase reporter assay, qPCR, and Western blotting. Moreover, restoration of YWHAZ could rescue the antiproliferation effect of miR-375. Conclusions The data provide the solid evidence that miR-375 plays a tumor-suppressive role in ccRCC progression, partially through regulating YWHAZ. This study expands the antitumor profile of miR-375, and supports its role as a potential therapeutic target in ccRCC treatment.
14-3-3 Proteins ; metabolism ; Carcinoma, Renal Cell ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Kidney Neoplasms ; pathology ; MicroRNAs ; physiology ; Phenotype

Objective To investigate the early diagnostic value of bronchoalveolar lavage for pulmonary aspergillosis in non-immunocompromised patients. The GM absorbances of recycled bronchoalveolar lavage fluid in different orders were compared, in order to estabilsh a uniform of broncholaveolar lavage in GM test. Methods We mainly focused on the patients (84 cases) confirmed as pulmonary infection by HRCT chest imageological examination from January 2016 to February 2017. They underwent the bronchoalveolar lavage before empirical or pathogenic antifungal therapy. Meanwhile, the lavage was collected in order of the first and the second tube. Then, BALF-GM test was performed. The GM absorbance (A) and I value of bronchoalveolar lavage fluid were detected by ELISA method. The GM test result of the first tube of bronchoalveolar lavage fluid was included into GM1 group and the GM test result of the second tube of bronchoalveolar lavage fluid was included into GM2 group. According to the standards, the patients were divided into case group (proven 2 cases, probable 7 cases, possible 13 cases) and non-IPA group (62 cases). The GM test diagnostic efficiency of bronchoalveolar lavage fluid collected in different orders were statistically analyzed between the case group and control group. Results The GM-I values showed significant difference between GM1 and GM2 groups (Z = -3.98, P = 0.000). the average rank I value of BALF-GM1 (1.78 ± 1.71) was significantly higher than the BALF-GM2. According to the ROC curve, the optimal cut-off of BALF-GM1 was 0.6, the sensitivity was 86.36％, the specificity was 93.55％, the positive predictive value was 82.61％ and the negative predictive value was 95.08％. The area under the curve of BALF- GM1 (0.941) was significantly higher than that of BALF-GM2 (0.798), indicating that the diagnostic efficiency of BALF-GM1 was higher. Conclusion The operation sequence of collecting bronchoalveolar lavage could affect the I value of BALF-GM test. The diagnostic efficiency of BALF-GM test result of the first tube of bronchoalveolar lavage fluid was higher and had the higher application value in the diagnosis of pulmonary aspergillosis.