[Progress on the safety and efficacy of bedaquiline for the treatment of drug-resistant tuberculosis in special populations].

Antimicrobial resistance in Mycobacterium tuberculosis is a serious threat to global tuberculosis(TB) control. WHO listed bedaquiline as one of the first-choice drugs for the treatment of MDR/RR-TB in 2018. Bedaquiline is marketed for adult patients with MDR-TB and XDR-TB. However, there are few studies of bedaquiline in adolescents, pregnant women, the elderly, and other special populations with drug-resistant TB. This paper aimed to review the effectiveness and safety of bedaquiline in the treatment of special populations of drug-resistant TB for the clinical use.

[Susceptibility of drug-resistant staphylococci isolated from different parts of the ocular anterior segment to common ophthalmic antibiotics].

Objectie To investigate the susceptibility of drug-resistant staphylococci isolated from different parts of the anterior segment to levofloxacin, tobramycin, cefazolin sodium, fusidic acid and clindamycin. Methods: Experimental Study. A total of 67 patients with anterior segment infection (33 cases of conjunctivitis, 6 cases of bacterial keratitis, 7 cases of blepharitis, 9 cases of neonatal dacryocystitis, 9 cases of neonatal dacryocystitis, 1 case of adult dacryocystitis and 11 cases of other infectious eye diseases) were collected from the conjunctival sac, cornea, eyelid margin and lacrimal sac. Minimum inhibitory concentration (MIC) determination of methicillin-resistant Staphylococcus (MRS) strains and ß-lactamase-producing (ß-Lac) strains by a micro-liquid-based method, according to the M100 standard of the American Institute for Clinical and Laboratory Standardization Susceptibility and resistance determinations were made. Data were statistically analyzed using Chi-square or Fisher's exact test. Results: Thirty-five MRS, 30 ß-Lac and 2 ß-Lac MRS isolates were identified from 67 multidrug-resistant Staphylococcus . There were 3, 9, 4, and 19 MRS isolates isolated from the lacrimal sac, cornea, eyelid margin and conjunctival sac, accounting for 3/4, 9/12, 4/8, 19/43 (44.2%) of the isolated sites respectively. There were 1, 3, 3, and 23 ß-Lac isolates, accounting for 1/4, 3/12, 3/8 and 23/43 (53.5%) of the isolated sites, respectively. The highest proportion of ß-Lac isolates isolated from patients with a diagnosis of conjunctivitis was 17 (25.3%) from the conjunctival sac. Among the MRS strains isolated from the cornea and lacrimal sac, 5 (7.5%) and 3 (4.5%) were from patients diagnosed with bacterial keratitis and neonatal tear, respectively. The number of MRS strains and ß-Lac isolates isolated from patients with a diagnosis of blepharitis were both 3 (4.5%) from the lid margin.Among the strains isolated from the eyelid margin and the conjunctival sac, drug-resistant Staphylococcus epidermidis was the main strain, the drug-resistant Staphylococcus aureus was the major isolates in lacrimal sac and cornea. Among the 35 MRS isoaltes, 25, 24, 12, 12, and 11 were sensitive to cefazolin sodium, fusidic acid, levofloxacin, clindamycin and tobramycin, and the sensitivity rates were 71.4%, 68.6%, 34.3%, 34.3% and 31.4%, the difference was statistically significant (χ2=22.756, P<0.001), The sensitivity rates of levofloxacin, tobramycin, cefazolin sodium, fusidic acid and clindamycin against MRS isolates from the anterior segment were both statistically significant differences (χ2=18.493, 11.594, 8.906, 9.841, 16.059; all P<0.05). The susceptibility rates of MRS isolates against five antibiotics was statistically significant differences (χ2=33.080, P<0.001). Among the 30 ß-Lac isolates, 27, 22, 19, 16, and 8 were sensitive to cefazolin sodium, fusidic acid, levofloxacin, tobramycin and clindamycin, and the sensitivity rates were 90.0 % , 73.3%, 63.3%, 53.3% and 26.7%, the difference was statistically significant (χ2=28.280, P<0.001). The sensitivity rates of five antibiotics against ß-Lac isolates from the anterior segment were both statistically significant differences (χ2=50.971, 24.543, 48.147, 44.899, 18.676; all P<0.001). The susceptibility rates of ß-Lac isolates against five antibiotics was statistically significant differences (χ2=23.383, P<0.001). The sensitivity of cefazolin sodium and fusidic acid against ß-Lac isolates were higher than MRS isolates. Conclusions: Cefazolin sodium and fusidic acid may be the best choice for the treatment of drug-resistant Staphylococcus isolated from anterior conjunctival sac, cornea, eyelid margin and lacrimal sac, especially for ß-Lac-producing drug-resistant Staphylococcus infection.

SOX2 gene expression and its role in triple negative breast cancer tissues.

The aim of this work was to study the expression of SOX2 gene in triple negative breast cancer and its role. One hundred and twenty specimens of paraffin-embedded triple negative breast cancer (TNBC) tissues were collected from Harbin Medical University Cancer Hospital, Heilongjiang, China between January 2014 and March 2018. The expression of SOX2 was detected using immunohistochemistry, and the relationship between the expression of SOX2 and clinical features was analyzed. Breast cancer cell lines (normal group, SOX2 interference group, SOX2 overexpression group) were cultured in vitro to detect the proliferation and cloning ability of the cell lines. The expression of SOX2 was related to lymph node metastasis and stage of breast cancer (P less than 0.05), but was not related to age, menopause or tumor size (P > 0.05); the expression of SOX2 in the overexpression group was significantly greater than that in the normal group after 72 hours, and no significant difference between the overexpression group and the interference group was observed. The number of clone cells with a diameter of 0.5 mm in the interference group was lower compared to the normal group, and that of the overexpression group was higher, but not significant. SOX2 is associated with the high invasiveness of breast cancer and can be used as a therapeutic target to inhibit the metastasis of cancer cells. SOX2 can promote the proliferation of breast cancer cells and affect the size of clone cells in its involvement in clone.

Haploidentical haematopoietic stem cell transplantation for the treatment of severe aplastic anaemia patients with high-risk factors who lack an HLA-matched sibling donor.

This study aimed to analyse the efficacy of haploidentical donor (HID) haematopoietic stem cell transplantation as a first-line treatment for severe aplastic anaemia (SAA) with high-risk factors (infection or very severe aplastic anaemia,VSAA) in patients who lack an HLA-matched sibling donor (MSD). The patients with infection were treated with anti-infection therapy, and allogeneic haematopoietic stem cell transplantation (HSCT) was carried out after the infection being effectively controlled was in accordance with the stable infection (SI) standard. A total of 44 SAA patients receiving MSD transplantation (n=19) and HID transplantation (n=25) were included in this study. There was no significant difference in neutrophil engraftment between the two groups [MSD vs. HID, 19 (11-38) vs. 22 (15-47).P=0.241], and the difference in platelet engraftment was statistically significant [MSD vs. HID, 11(7-33) vs. 20 (12-69), P=0.034]. The HID group exhibited a higher incidence of grade II-IV acute graft-versus-host disease (aGVHD) (HID vs. MSD, 48.0% vs10.5%, P=0.034)and a higher incidence of chronic GVHD (cGVHD) than the MSD group (64.0% vs. 21.1%, P=0.026). There was no significant difference between overall survival (OS) following HID and MSD transplantation (84.0% vs. 89.5%, P=0.664) and failure-free survival (FFS)(80.0% vs. 84.2%, P=0.965). The interval from diagnosis to transplantation (>50d) and ECOG (>2) were independent factors associated with OS and FFS. HID HSCT may be an effective and safe option for SAA patients with high-risk factors who lack an MSD.

[The diagnostic value of whole blood Epstein-Barr virus DNA load in lymphoproliferative diseases after allogeneic hematopoietic stem cell transplantation].

Objectives: To investigate the diagnostic value of whole blood quantitative PCR for DNA load of Epstein-Barr virus (EBV) in post-transplant lymphoproliferative disease (PTLD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: A total of 694 patients with hematologic diseases who underwent allo-HSCT at the Hematology Department of Peking University First Hospital from April 2004 to April 2019 were included, and their data were retrospectively analyzed. Results: ①Among the 694 cases, 29 cases (22 males and 7 females, with a median age of 22 (1-52) years) developed PTLD after allo-HSCT with a cumulative incidence of 4.2% and a median onset time of 2.1 (0.8-20.6) months. ② Univariate analysis showed that age<30 years, diagnosis with aplastic anemia, human leukocyte antigen (HLA) mismatch, use of antithymocyte globulin (ATG) in preconditioning regimens, and EBV reactivation were the risk factors for the occurrence of PTLD. Multivariate analysis showed that EBV reactivation was an independent risk factor for the occurrence of PTLD. ③Further analysis of EBV reactivation cases showed that the peak value of EBV-DNA load was significantly higher in the PTLD group than that in the non-PTLD group (P<0.001) and the incidence of PTLD increased with the increase of EBV-DNA load. Receiver operating characteristic (ROC) curve analysis indicated that PTLD was more likely to be diagnosed when the EBV-DNA load was >1.19×10(6) copies/ml (sensitivity 0.800 and specificity 0.768) . ④All patients with PTLD received rituximab-based treatment, with an overall response rate of 86.2% and an overall survival rate of 54.3%. Conclusion: The PTLD occurrence after allo-HSCT is highly correlated with EBV reactivation, and the higher the EBV-DNA load, the greater the risk of PTLD occurrence. The dynamic monitoring of EBV-DNA load plays an important role in predicting PTLD occurrence.

The reduced lncRNA NKILA inhibited proliferation and promoted apoptosis of chondrocytes via miR-145/SP1/NF-κB signaling in human osteoarthritis.

OBJECTIVE: Growing evidence has shown that long non-coding RNAs (lncRNAs) play some roles in the progression of osteoarthritis. In this study, we investigated the functions and mechanisms of lncRNA NKILA (NKILA) of chondrocytes in human osteoarthritis (OA). PATIENTS AND METHODS: RT-PCR was used to detect the expressions of NKILA and miR-145 in OA tissues. After transfection of NKILA overexpression lentivirus (LV-NKILA) and NKILA downregulation lentivirus (LV-shNKILA) into primary chondrocytes, MTT assay was carried out to measure the cell proliferation of chondrocytes. The expressions of SP1, Bcl-2, Bax, cleaved caspase-3 and NF-κB signaling factors were detected by Western blot. Moreover, luciferase assay was performed to explore the binding site of NKILA and miR-145, miR-145 and SP1. Finally, JSH, a NF-κB signaling inhibitor, was added into chondrocytes transfected with LV-shNKILA or miR-145 mimic to detect that NKILA functions via miR-145/SP1/NF-κB signaling pathway. RESULTS: We found that NKILA and SP1 were significantly reduced, miR-145 was increased in cartilage tissues of OA patients. After LV-NKILA transfection, the proliferation ability of chondrocytes was improved and cell apoptosis was inhibited; however, the proliferation ability of chondrocytes was repressed, and cell apoptosis was increased in LV-sh NKILA group. MiR-145 was predicted to be a potential target of NKILA and luciferase gene reporter assay confirmed that NKILA could directly bind with miR-145. Furthermore, SP1 was predicted to be a target gene of miR-145 and luciferase gene reporter assay proved that miR-145 could directly bind with SP1. Finally, we added JSH, a NF-κB signaling inhibitor, into chondrocytes with LV-shNKILA or miR-145 mimic. Results showed that the repressed SP1 was reversed after the addition of JSH in both LV-shNKILA and miR-145 mimic group. Further, the repressed proliferation capacities and promoted cell apoptosis were also reversed after the addition of JSH. CONCLUSIONS: According to the results, this study uncovers NKILA is reduced in human osteoarthritic cartilage tissues. Furthermore, we firstly uncover that the reduced NKILA could function as a ceRNA to improve miR-145, which inhibited SP1 expression and regulated NF-κB signaling pathway, thereby promoting tissue inflammation, and inhibiting proliferation and promoting apoptosis of chondrocytes. Thus, it may be used as a promising prognostic marker and a potential target for osteoarthritis.

[Clinical analyses of 263 patients with laryngeal leukoplakia].

Objective: To investigate the etiology, clinical and pathological characteristics of laryngeal leukoplakia and the predictive risk factors of recurrence and malignant transformation. Methods: Clinical data of 263 patients with laryngeal leukoplakia between January 2000 and December 2015 were analyzed retrospectively. Results: The pathological diagnoses included squamous epithelial hyperplasia (54.4%), mild dysplasia (17.9%), moderate dysplasia (12.2%), severe dysplasia and carcinoma in situ (12.5%), and invasive carcinoma (3.0%). Age and the extent of lesion were statistically different among different pathological groups (P<0.05). Gender, smoking and alcohol consumption did not show statistical differences among different pathological groups (P>0.05). Follow-up of 215 patients, excluding 6 cases of invasive carcinoma. The recurrence rate was 20.6%(43/209), and the malignant transformation rate was 5.3%(11/209). Multivariate analysis showed that pathological classification of moderate to severe dysplasia was the independent risk factor for recurrence and malignant transformation of laryngeal leukoplakia (P<0.05). In patients with severe dysplasia and carcinoma in situ, the recurrence proportion of conservative treatment, vocal cords (partial) resection and radiotherapy were 8/10, 0/10 and 2/11 respectively. Conclusions: Laryngeal leukoplakia occurs frequently in elderly men with long-term smoking history. Pathological diagnoses are different. The grade of dysplasia is the predictive risk factor for the recurrence and malignant transformation of laryngeal leukoplakia. More aggressive treatment and closer follow-up should be warranted for patients with moderate dysplasia, severe dysplasia and carcinoma in situ.

[Treatment of children's pharyngeal stenosis following pharyngeal surgery with coblation].

Objective:Pharyngeal stenosis as a postoperative complication following pharyngeal surgery (tonsillectomy/adenoidectomy) with coblation is rare and may be difficult to treat. This report is to explore the causes of pharyngeal stenosis and presents our successful treatment experience. Method:From Jan 2012 to July 2016, 5 children with pharyngeal stenosis (2 nasopharyngeal stenosis and 3 nasopharyngeal stenosis combined with oropharyngeal stenosis) secondary to pharyngeal surgery (tonsillectomy/adenoidectomy) in Peking Union Medical College Hospital were analyzed. Five cases with severe nasopharyngeal stenosis received surgery of scar resection, horizontal-to-vertical pharyngoplasty and local pharyngeal flap rotation; and three of them received free skin transplantation. After stenosis repair surgery, prolonged nasopharyngeal hollow stents were used for more than 6 months. To evaluate the therapeutic effect, pharyngeal cavities and symptoms of difficulty nasal breathing, mouth breathing, difficulty in blowing nose, hyponasal speech, snoring, restless sleep, anosmia, dysphagia were assessed and compared before and after surgery. Result:With 7-46 months follow-up, all symptoms of the 5 cases are ameliorated and the diameters of nasopharyx are more than 1.5 cm. No velopharyngeal insufficiency complication happened. Conclusion:Improper operation with coblation can cause severe pharyngeal stenosis. Flap rotation, horizontal-to-vertical pharyngoplasty and prolonged use nasopharyngeal hollow stents are reliable methods to correct pharyngeal stenosis following children's pharyngeal surgery.

[Transoral coblation-assisted endoscopic minimally invasive surgery for superficial tongue base tumours].

Objective: To introduce the method of transoral coblation-assisted endoscopic minimally invasive surgery for superficial tongue base tumour. Methods: A total of 15 patients treated with transoral coblation-assisted endoscopic minimally invasive surgery from Mar. 2006 to Aug. 2016 were retrospectively reviewed. There were 9 patients with malignant tumors, 6 patients with benign neoplasms. Adjuvant postoperative radiation therapy was applied in three cases of squamous cell carcinoma, neck was performed in four cases of cancer. One case of non-Hodgkin lymphoma received postoperative chemotherapy. Results: One case with ectopic thyroid gland was treated by subtotal resection and one case with squamous cell carcinoma changed into open surgery because of major lingual artery bleeding. The En bloc resection under edoscope was achieved in 92.86%(13/14)of patients. Fifteen cases of neoplasms were followed-up for 8-50 months(median 20 months), one patient with Cowden syndrome was lost to follow-up because of appendical carcinoid combined pulmonary metastasis, one patient with non-Hodgkin lymphoma died of recurrence in other head neck areas 2 years after chemotherapy. Conclusion: Transoral coblation-assisted endoscopic surgery can successfully treat for the patients with superficial tongue base tumours.

[Laryngeal endoscopic cricopharyngeal myotomy for cricopharyngeal achalasia post stroke].

Objective: To explore the safety and validity of endoscopic cricopharyngeal myotomy in patients with cricopharyngeal achalasia. Methods: A total of 19 patients with cricopharyngeal achalasia suffered from sustained dysphagia were enrolled in this study. The patients were divided into transcervical cricopharyngeal myotomy(CPM) group and endoscopic CPM (ECPM) group. Swallowing function and complications were evaluated.SPSS7.0 software was used to analyze the data. Results: The swallowing function improved significantly in seven patients in ECPM group, and 9 patients improved in CPM group.The video fluoroscopic swallowing study(VFSS)-swallowing score, VFSS-aspiration score and drinking test score were (3.1±1.1), (3.4±0.8) and (2.0±0.6)in post-ECPM, (3.4±1.4), (3.0±0.9) and (2.2±0.6)in post-CPM. No statistical difference was found in validity between CPM group and ECPM group(t=-0.435, t=1.086, t=-0.607, P>0.05). No statistical difference was observed on the occurrence of complication between two groups. Only one patient had subcutaneous emphysema after operation in ECPM. Conclusions: New surgical instruments and endoscopic surgical technique were safe and effective for cricopharyngeal achalasia. Because these instruments are cheaper, laryngeal endoscopic cricopharyngeal myotomy is easier to be popularized more easily than microscopic laser assistted CPM.

[Transoral endoscopic minimally invasive surgery for hypopharyngeal postcricoid and upper esophageal lesions].

Objective:To describe the therapeutic effect of transoral endoscopic minimally invasive surgery for hypopharyngeal postcricoidarea and upper esophageal lesions. Method:Transoral endoscopic minimally invastive surgery was carried out in fifteen patients.There were 7 patients with primary tumors on the postcricoid area, including three squamous cell carcinoma（2 cases T2N0M0，1 case T2N2cM0），two cavernous hemangioma, one giant fibrovascular polyp and one recurrent lipofibroma. The transoral endoscopic tumors resection en bloc was performed in all of them. Adjuvant postoperative radiation therapy was applied in cases of cancer, and bilateral neck dissections was performed in the T2N2cM0 case; There were other eight patients with upper esophageal lesions , seven cases dysphagia was caused by stroke and one case was Zenker diverticulum, treated by endoscopic cricopharyngeal myotomy ordiverticulotomy. Result:The en bloc resection endoscopically was achieved in all of patients with tumors on the postcricoid area. All surgical resection margins were negative.The two cases of postcricoid cancer and four benign tumor were followed up 16-30 months and 2-12 months respectively, and all of the cases were not local recurrence. A recent patient with postcricoid cancer had not finished postoperative adjuvant radiation therapy. The endoscopic cricopharyngeal myotomy was effective in 4 out of 7 patients,nasogastric feeding was no longer required.Significant improvement occurred in Zenker diverticulotomy patient, due to the return of physiological deglutition, and Barium swallow study showing disappearance of the diverticulum after one month.The effects of minimally invasive threatment were satisfactory,such as not need tracheotomy and early oral feeding, shorter hospital stay and less postoperative complications. Conclusion:Transoral endoscopic surgery is minimally invastive, safe and effective treatment alternative for some hypopharyngeal postcricoid area and upper esophageal lesions.

catena-Poly[[bis(thiocyanato-N)-lead(II)]-mu-1,2-bis(4-pyridyl)-ethane-N:N'].

In the title coordination polymer, [Pb(NCS)(2)(C(12)H(12)N(2))], the coordination geometry about the Pb(II) atom is a distorted octahedron, composed of two N atoms from bpe ligands [bpe is 1,2-bis(4-pyridyl)ethane], two other N atoms from NCS(-) groups and two neighbouring S atoms through short contacts. The trans-bpe ligands act as bridges between two Pb(II) centres resulting in the formation of a linear chain. The terminal S atoms of the NCS(-) ligands make short contacts with the Pb(II) atom of neighbouring chains to form an infinite two-dimensional polymeric structure.