Objective To explore the clinical characteristics of patients with alcoholic liver disease(ALD)of various traditional Chinese medicine(TCM)syndrome types.Methods A retrospective analysis was conducted in 129 patients with alcoholic liver disease who met the inclusion and exclusion criteria in Foshan Hospital of Traditional Chinese Medicine from 2018 to 2022.The general data of the patients as well as their TCM syndrome types and clinical information of liver and kidney function,blood lipid,liver transient elastography during the hospital visit were collected.The distribution of TCM syndrome types in ALD patients was analyzed,and the clinical characteristics of the ALD patients with various TCM syndrome types were explored.Results(1)Of the 129 patients,128(99.22%)were male and only one(0.78%)was female,the average age was(48.71±11.50)years old,and the average body mass index(BMI)was(23.82±3.98)kg·m-2.(2)Damp-heat accumulation syndrome was most common syndrome type in ALD patients,with a total of 70 cases(54.26%),and then came liver depression and spleen deficiency syndrome(24 cases,18.60%),internal obstruction of phlegm-damp syndrome(22 cases,17.05%),liver-kidney sufficiency syndrome(7 cases,5.43%),phlegm interweaved with blood stasis syndrome(3 cases,2.33%),and internal accumulation of blood stasis syndrome(3 cases,2.33%).(3)The analysis of clinical characteristics by non-parametric rank sum test showed that there were no statistically significant differences in BMI,alcohol consumption,aspartate aminotransferase(AST),gamma-glutamyltransferase(GGT),total bilirubin(TBIL),alkaline phosphatase(ALP),triglyceride(TG),liver stiffness measurement(LSM),and controlled attenuation parameter(CAP)which reflects the fat content of liver in ALD patients with various TCM syndrome types(P＜0.05 or P＜0.01).The prominent features were as follows:patients with the 4 types of liver depression and spleen deficiency,internal obstruction of phlegm-damp,phlegm interweaved with blood stasis,and internal accumulation of blood stasis had a BMI exceeding the standard(＞24 kg·m-2),whereas patients with damp-heat accumulation syndrome and liver-kidney deficiency syndrome,which accounted for 54.26%of the sample size,had a BMI within the normal range(23.03 kg·m-2 and 21.42 kg·m-2,respectively),and the BMI of these two types differed from that(26.44 kg·m-2)of the internal obstruction of phlegm-damp syndrome(P＜0.01),suggesting that more than half of the ALD patients had the normal BMI;moreover,the patients with internal obstruction of phlegm-damp also had the highest values of serum TG(2.69 mmol/L)and CAP(292 db/m)except for the highest BMI,indicating that patients with internal obstruction of phlegm-damp syndrome had a more serious degree of obesity and hepatic fat infiltration than those with other syndrome types;the levels of AST and GGT,which separately reflect the chronic inflammatory injury of liver and bile duct cell injury,were significantly increased in the patients with damp-heat accumulation syndrome and liver-kidney deficiency syndrome,and the LSM value of these two types of patients was also the highest in all of the syndrome types,the differences being all statistically significant(P＜0.05 or P＜0.01).Conclusion Damp-heat accumulation syndrome is the main TCM syndrome type of ALD patients,the degree of fatty infiltration of the liver and overweight of ALD patients are not corresponded to the severity of illness,and there are some differences in the clinical indicators of ALD patients with various TCM syndrome types.However,with cross reference to the data of the four diagnostic examinations of TCM and the clinical indicators,the accuracy of the TCM diagnosis of ALD is expected to be increased.

A pharmacophore-based study was conducted to investigate the therapeutic activity of the traditional Tibetan medicine Zha Xun (ZX) in liver diseases. In the present study, the protective effect of ZX on the acute liver injury induced by concanavalin A (ConA) and 0.15% carbon tetrachloride (0.15% CCl₄) in ICR mice was evaluated, and the results showed that ZX significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the ConA-induced acute immune liver injury model and the CCl₄-induced acute oxidative liver injury model (P < 0.05). Subsequently, the protective effects of aqueous, 95% ethanol, 60% ethanol and 30% ethanol eluting fractions of ZX, and fulvic acid, the main water-soluble constituent of ZX, were evaluated against acute oxidative liver injury induced by 0.15% CCl₄ in mice. The results showed that different solvent-eluting fractions of ZX showed certain hepatoprotective activities, among which the aqueous extract of ZX and 30% ethanol extract of ZX significantly reduced the serum levels of ALT, AST, and lactate dehydrogenase (LDH) in mice (P < 0.05), and the serum levels of LDH in mice were significantly reduced by fulvic acid (P < 0.05), which showed significant hepatoprotective activity. The protective activities and preliminary mechanisms of the total extract of ZX, the aqueous extract of ZX, the 30% ethanol extract of ZX, and fulvic acid against hepatocellular injury in vitro were further evaluated by using the H₂O₂-induced hepatocellular injury model. The results showed that the components could significantly inhibit H₂O₂-induced hepatocellular injury, reduce the levels of ALT, alkaline phosphatase (ALP), and LDH, improve the survival rate of hepatocellular cells, and reduce the content of intracellular reactive oxygen species (ROS) in cell culture. At the same time, it can inhibit hepatocyte apoptosis by increasing the expression ratio of Bcl-2/BAX protein and decreasing the expression ratio of cleaved caspase-3/pro caspase-3 protein. The present study showed that ZX has clear hepatoprotective activity in vitro and in vivo, and the different solvent elution fractions of ZX showed certain hepatoprotective activity, among which the aqueous extract of ZX, 30% ethanol extract of ZX had better hepatoprotective activity, and the activity of 60% ethanol extract of ZX was stronger than that of 95% ethanol extract of ZX. The activity of ZX and its water-soluble elution site exerted hepatoprotective effects by inhibiting hepatocyte apoptosis and oxidative stress. The animals used in this experiment and related disposal meet the requirements of animal welfare, and have been reviewed and approved by the Laboratory Animal Management and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: 00004018).

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

INTRODUCTION: Evidence regarding the efficacy of high-flow nasal cannula (HFNC) oxygenation for preoxygenation and apnoeic oxygenation is conflicting. Our objective is to evaluate whether HFNC oxygenation for preoxygenation and apnoeic oxygenation maintains higher oxygen saturation (SpO₂) during rapid sequence intubation (RSI) in ED patients compared to usual care. METHODS: This was a multicentre, open-label, randomised controlled trial in adult ED patients requiring RSI. Patients were randomly assigned 1:1 to either intervention (HFNC oxygenation at 60L/min) group or control (non-rebreather mask for preoxygenation and nasal prongs of at least 15L/min oxygen flow for apnoeic oxygenation) group. Primary outcome was lowest SpO₂ during the first intubation attempt. Secondary outcomes included incidence of SpO₂ falling below 90% and safe apnoea time. RESULTS: One hundred and ninety patients were included, with 97 in the intervention and 93 in the control group. Median lowest SpO₂ during the first intubation attempt was 100% in both groups. Incidence of SpO₂ falling below 90% was lower in the intervention group (15.5%) compared to the control group (22.6%) (adjusted relative risk=0.68, 95% confidence interval [CI] 0.37-1.25). Post hoc quantile regression analysis showed that the first quartile of lowest SpO₂ during the first intubation attempt was greater by 5.46% (95% CI 1.48-9.45%, P=0.007) in the intervention group. CONCLUSION Use of HFNC for preoxygenation and apnoeic oxygenation, when compared to usual care, did not improve lowest SpO₂ during the first intubation attempt but may prolong safe apnoea time.
Adult ; Cannula ; Emergency Service, Hospital ; Humans ; Intubation, Intratracheal ; Rapid Sequence Induction and Intubation ; Respiration, Artificial

Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.
Asthenozoospermia/pathology* ; Dyneins/genetics* ; Homozygote ; Humans ; Male ; Microtubule-Associated Proteins ; Mutation ; Mutation, Missense ; Sperm Tail/metabolism*

Objective:To investigate the effect of flap combined with 3D printed microporous titanium(tantalum)prosthesis in the treatment of lower extremity soft tissue defect with large bone defect.Methods:From January 2019 to December 2020, 2 patients with large soft tissue defects on dorsal foot together with large metatarsal bone defect and 4 patients with soft tissue defects of calf with large tibial bone defect were treated. The areas of soft tissue defect were 5.0 cm×8.0 cm-15.0 cm×10.0 cm. The length of the bone defect were 3.8 cm to 7.0 cm, 5.75 cm in average. In the first stage, metatarsal bone defect or tibial bone defect was filled with vancomycin blended bone cement, meanwhile, soft tissue defect was repaired with anterolateral femoral flap(ALTF) with vascular anastomosis in 2 cases of feet, and local fascia flap was trans-positioned in 4 cases of lower extremity defects. The sizes of repairing flap were 6.0 cm×8.5 cm-16.0 cm×11.0 cm. Two to 7 months after the initial surgery, the customer designed microporous titanium prostheses were used(5 cases with microporous titanium and 1 with microporous tantalum) to repair the bone defects. The wound healing, the integration of metatarsal and tibial fractures with 3D printed microporous titanium(tantalum) prostheses, and the walking condition were observed after surgery. The follow-up lasted from 6 to 25 months, with an average of 12.7 months.Results:The wound healing in 5 patients was good. The patients stood on the foot in 2 months after surgery, started to walk with the assistance of crutch in 3 months after surgery, and took walk without assistance in 5-6 months after surgery. Good osseous integration were achieved. One diabetic patient had infection of foot wound 3 months after surgery. After removal of microporous titanium prosthesis and replacement of vancomycin blended interstitial substance of bone cement, the wound healed and the patient resumed walking.Conclusion:It is an effective method to encourage the patients to take early ambulation after the surgery for lower extremity soft tissue defect with large bone defect that was repaired by a flap and 3D printed microporous titanium(tantalum)prosthesis. Further observations are required to investigate the long-term efficacy, and the reduction of prosthesis infection rate requires further exploration.

Carcinoma, Intraductal, Noninfiltrating ; Humans ; Salivary Gland Neoplasms/diagnosis* ; Salivary Glands

The ribose and phosphorus contents in Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) are two important chemical indexes for the development and quality control of Hib conjugate vaccine. A quantitative ¹H- and ³¹P-NMR method using a single internal standard was developed for simultaneous determination of ribose and phosphorus contents in Hib CPS. Hexamethylphosphoramide (HMPA) was successfully utilized as an internal standard in quantitative ¹H-NMR method for ribose content determination. The ribose and phosphorus contents were found to be affected by the concentration of polysaccharide solution. Thus, 15-20 mg·L^-1 was the optimal concentration range of Hib CPS in D₂O solution for determination of ribose and phosphorus contents by this method. The ribose and phosphorus contents obtained by the quantitative NMR were consistent with those obtained by traditional chemical methods. In conclusion, this quantitative ¹H- and ³¹P-NMR method using a single internal standard shows good specificity, accuracy and precision, providing a valuable approach for the quality control of Hib glycoconjugate vaccines.
Haemophilus Vaccines ; Haemophilus influenzae type b ; Phosphorus ; Polysaccharides, Bacterial ; Ribose

Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

The clinical symptoms and signs of methamphetamine-associated psychosis (MAP) and schizophrenia are highly similar, but the situation is completely different when MAP and schizophrenia patients need to be assessed for criminal responsibility after they comitted a harmful behavior. Therefore, the distinction between the two psychoses is very important in forensic psychiatry. At present, the identification of these two psychoses is mainly dependent on the corresponding criteria such as the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the Chinese Classification of Mental Disorders Version 3 (CCMD-3). It's challenging to diagnose and distinguish between the two in practical cases due to their similar clinical symptoms and the lack of effective objective indexes. Different from the limitations of single omics, integrative omics intergrates data from multiple dimensions and has been extensively studied in the field of schizophrenia and has achieved some preliminary results. In view of the correlation between MAP and schizophrenia and the potential application value of integrative omics, this paper proposes an integrative omics strategy for MAP pathogenesis and forensic identification, aiming to improve the further understanding of the relationship between the two psychoses and the corresponding pathogenesis. It also provides references for the future exploration of integrative omics in forensic precise identification and effective monitoring and early warning methods.
Humans ; Methamphetamine/adverse effects* ; Psychoses, Substance-Induced/etiology* ; Psychotic Disorders/genetics* ; Schizophrenia/genetics* ; Diagnosis, Differential