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.

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 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

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 analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group (P=0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7%vs 79.7%, P<0.05) and higher excellent partial response (76.2%vs 55.1%, P<0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups (P>0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group (P<0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement (P<0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.
Amyloidosis/diagnosis* ; Humans ; Immunoglobulin Light Chains ; Immunoglobulin Light-chain Amyloidosis/therapy* ; Multiple Myeloma/therapy* ; Prognosis ; Retrospective Studies

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

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