italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

OBJECTIVE: To evaluate the effectiveness and safety of Zhenqi Buxue Oral Liquid (ZQ), progesterone capsules, and their combination in treating oligomenorrhea and hypomenorrhea with qi-blood and Kidney (Shen) essence deficiency. METHODS: This was a prospective, randomized, multi-center controlled trial between June 2022 to December 2022. Ninety-six oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency were randomly assigned to receive ZQ (ZQ group, 29 cases), progesterone capsules (PG group, 32 cases), or the combined Chinese and Western medicine (COM group, 31 cases) at a ratio of 1:1:1. Patients in the ZQ or PG group took daily 10 mL twice a day of ZQ or 200 mg once a day of progesterone capsules for 10 consecutive days on day 15 of the menstrual cycle respectively, and patients in the COM group received the same ZQ combined with progesterone capsules. The treatment course lasted for 3 months and follow-up was performed at 1 and 3 months after the end of treatment. Primary endpoint was the menstrual Traditional Chinese Medicine Syndrome Scale (TCMSS) scores. Secondary endpoints included pictorial blood loss assessment chart (PBAC) scores, clinical efficacy rate, 36-item Short Form Health Survey (SF-36) scores, sex hormones and thickness of endometrium. Adverse events (AEs) were recorded. RESULTS: TCMSS scores after 1- and 3-month treatment in all groups were significantly lower than those at baseline (P<0.05). Only TCMSS scores after 3-month treatment in the ZQ and COM groups continuously decreased compared with those after 1-month treatment in the same group (P<0.01). TCMSS scores after 3-month treatment in the ZQ and COM groups were significantly lower than those in the PG group (P<0.05, P<0.01). Compared with baseline, PBAC scores in the ZQ and COM groups after 3 months of treatment were also significantly higher (both P<0.01). The total effective rates of TCM syndrome of 3-month treatment were significantly improved in all groups compared with that after 1 month of treatment (P<0.05). The total effective rate of the COM group was the highest in the 3rd month of treatment and significantly higher than that of PG group alone (P<0.05). Compared with baseline, only the SF-36 scores of COM group were significantly improved after 3 months of treatment (P<0.05). No serious adverse reactions were observed after treatment. CONCLUSIONS The combination of ZQ and PG, or ZQ only had better effects on reducing TCMSS scores compared with PG, and COM showed the higher total effective rate compared with monotherapy. Besides, COM could effectively improve menstrual blood loss and quality of life. ZQ combined with PG may be an effective and safe option for oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency.
Female ; Humans ; Progesterone/therapeutic use* ; Qi ; Oligomenorrhea/drug therapy* ; Quality of Life ; Prospective Studies ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/adverse effects* ; Capsules ; Kidney

Humans ; Multiple Myeloma/genetics* ; Neoplasm, Residual/diagnosis* ; Flow Cytometry ; High-Throughput Nucleotide Sequencing

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*

Humans ; Multiple Myeloma/drug therapy* ; Bendamustine Hydrochloride/therapeutic use* ; Neoplasm Recurrence, Local/drug therapy* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214⁺AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214⁺AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214⁺AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214⁺AL. Disease recurrence is the most important factor affecting long-term survival.
Male ; Female ; Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/methods* ; Leukemia, Myeloid, Acute/therapy* ; Survival Analysis ; Remission Induction ; Acute Disease ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Recurrence ; Nuclear Pore Complex Proteins

Persistent Müllerian duct syndrome (PMDS) is a rare clinically and genetically overlapping disorder caused by mutations in the anti-Müllerian hormone (AMH) gene or the anti-Müllerian hormone receptor type 2 (AMHR2) gene. Affected individuals present uterus and tubes in normally virilized males and are discovered unexpectedly during other surgeries. Since it is rare and complex, a definitive clinical diagnosis can be missed, and there are no guidelines regarding how to deal with the uterus. In the present study, exome sequencing and Sanger verification were performed for causal variants in 12 PMDS patients. Preoperative diagnoses were made by positive exome sequencing in 8 patients. Of them, 7 patients evoked on the basis of ultrasound indicating bilateral testes on the same side of the body. Twelve different AMH variants (2 frameshift/nonsense, 1 deletion, 8 missense, and 1 in-frame) in 9 patients and 6 different AMHR2 variants (5 missense and 1 splicing) in 3 patients were identified. Seven variants were classified as "pathogenic" or "likely pathogenic", and 4 of them were novel. All but two patients with AMH defects showed low serum AMH concentrations, but all patients with AMHR2 defects showed elevated AMH levels. During surgery, an abnormal vas deferens was observed in half of the patients. Eight patients underwent orchidopexy with uterine preservation. Of them, 2 patients presented complications including irreducible cryptorchidism, and 3 patients developed Müllerian remnant cysts. Three patients underwent subtotal hysterectomy. Of them, one patient had complication of injury to the vas deferens, and one had hemorrhage after operation. This is the first report of PMDS involving a large Chinese population. The present study not only expands the variation spectrum but also provides clinical experience about the management of the uterus.
Anti-Mullerian Hormone ; China ; Disorder of Sex Development, 46,XY/surgery* ; Female ; Humans ; Male ; Ultrasonography

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.
Male ; Female ; Humans ; Middle Aged ; Adult ; Aged ; Cysteine ; Multiple Myeloma/diagnosis* ; Reproducibility of Results ; Metabolome ; Metabolomics/methods* ; Metabolic Networks and Pathways ; Methionine ; Serine ; Phenylalanine ; Threonine ; Biomarkers

Abstract: Objective　To analyze the pathogenic characteristics and epidemiological significance of human plague related strains in Qinghai Province in recent 30 years, so as to provide scientific basis for on-the-spot disposal and prevention and control measures of plague outbreak in Qinghai Province. Methods　A total of 35 strains of Yersinia pestis isolated from 29 typical human plague outbreaks in Qinghai Province from 1980 to 2011 were selected and studied by biochemical fermentation experiments. Virulence factors detection of Fraction 1 antigen (Fra1), virulence antigen (VW), pigmentation (Pgm) and Yersinia pestis Ⅰ (PstⅠ), determinants and genotyping of differential regions (DFRs) were used to study the pathogenic characteristics. At the same time, according to the epidemic situation of human and animal plague in Qinghai Province in recent years, the current situation of plague prevention and control and epidemic characteristics were analyzed. Results　The biotypes of 35 strains of Yersinia pestis were classical, and the biotypes of 29 strains (82.86%) were of Qinghai-Tibet Plateau type, mainly distributed in southern Qinghai and around lake areas, 2 strains (5.71%) belonged to Qilian Mountains type, mainly distributed in Qilian mountains, and 6 genotypes were identified by DFR. Among them, 16 were type 5, 12 were type 8, 2 were type 10, 1 was type 36, 3 were type 30 and 1 was type 1b, the strains of type 5 and 1b were mainly distributed around the lake and the southern foot of Qilian Mountains, while the strains of type 8, 10, 36 and 30 were mainly distributed in the southern part of Qinghai. Conclusions　The pathogen of Yersinia pestis in Qinghai Plateau has complex biochemical types, the epidemic situation among animals is continuous year after year, the situation of prevention and control is serious, the occurrence and prevalence of plague seriously endanger people's health and social development, so it is necessary to do a solid job in the prevention and control of plague to ensure the safety of people's lives.

Objectives: To compare the short-term outcomes of branched stentgrafts for left subclavian artery (LSA) revascularization or partial LSA coverage without reconstruction in the treatment of type B aortic dissection with proximal tear close to LSA. Methods: A total of 125 type B aortic dissection patients were treated with thoracic endovascular aortic repair (TEVAR) in Xinqiao Hospital of the Army Medical University from January 2019 to March 2021. Their medical records were reviewed and the outcomes were followed up. According to the different treatment methodologies, the patients were divided into complete LSA coverage with reconstruction group (n=25) and partial LSA coverage without reconstruction group (n=100). The data of baseline characteristics, clinical outcomes, and incidence of postoperative in-hospital adverse events were collected and compared between the two groups. The adverse events during one-year follow-up were also compared between the two groups. Kaplan-Meier analysis and log-rank test were used to compare the cumulative survival rates between groups. Results: Compared with partial LSA coverage group, distance of proximal tear to LSA((8.69±2.32)mm vs. (13.77±1.71) mm) was shorter, in-hospital expenses[175 400(166 000-189 900) yuan vs. 143 700 (138 100-151 800) yuan] was higher, average length of stent [200.00 mm vs. 150.00 (150.00-150.00) mm] and operation time [155.00 (140.00-170.00) min vs. 95.00 (80.00-100.00) min] were longer, and volumes of contrast agent [300.00 (200.00-300.00) ml vs. 200.00 (200.00-300.00) ml] (P<0.05) were higher for patients in the complete LSA coverage with reconstruction group. The incidence of post-operative fever was significantly higher in complete LSA coverage with revascularization group than that in partial LSA partial coverage with reconstruction group (56% vs. 25%, P=0.003). There was no significant difference in the incidences of all-cause death, stroke, endoleak, paraplegia, and LSA branch vessel occlusion between the two groups during follow-up. Kaplan-Meier analysis showed that there was no significant difference in the cumulative survival rates between the two groups (log-rank test: P=0.572 5). Conclusion: The TEVAR with complete LSA revascularization or partial LSA coverage without reconstruction for type B aortic dissection close to LSA are safe and effective with high success rates. There is no significant difference between these two techniques in short-term outcomes.
Aortic Dissection/surgery* ; Aortic Aneurysm, Thoracic/surgery* ; Blood Vessel Prosthesis Implantation/methods* ; Endovascular Procedures/methods* ; Humans ; Retrospective Studies ; Stents ; Subclavian Artery/surgery* ; Time Factors ; Treatment Outcome