[Study on the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A].

Objective: To summarize the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A. Methods: In the retrospective study, a total of 1 226 clinical isolates from suspected multidrug-resistant pulmonary tuberculosis patients in Beijing TB control system from 2016 to 2021 were identified as Mycobacterium tuberculosis (MTB) strains by MPB64 antigen detection test. Rifampicin-resistant tuberculosis (RR-TB) strains were screened by the phenotypic drug susceptibility using the proportion method. The drug susceptibilities of Levofloxacin(LFX), Moxifloxacin(MFX), Bedaquiline(BDQ) and Linezolid(LZD)were detected by the phenotypic drug susceptibility with microplate method. The drug resistance rate, drug resistance level and minimum inhibitory concentration (MIC) distribution of four anti-tuberculosis drugs in group A were analyzed. We calculated the demographic distribution of RR-TB, multidrug-resistant tuberculosis(MDR-TB), pre-extensively drug resistant tuberculosis (pre-XDR-TB), extensively drug resistant tuberculosis (XDR-TB) patients and the cross resistance of LFX and MFX, then summarized the drug-resistance spectrum of BDQ-resistant and LZD-resistant strains and the treatment outcome of RR-TB patients. Measurement data were expressed as rate or composition ratio,χ2 test was used between and within groups, and P<0.05 was considered statistically significant. Results: Among the 1 226 suspected multidrug-resistant pulmonary tuberculosis patients, the detection rates of RR/MDR/pre-XDR/XDR-TB patients were 20.8%(255/1 226), 15.2%(186/1 226), 5.7%(70/1 226), 0.5%(6/1 226), respectively. There were statistically significant differences in the distribution of patients with the four types of drug resistance in terms of age and treatment history (χ2=14.95, P=0.020;χ2=15.91, P=0.001). The drug resistance rates of LFX, MFX, BDQ and LZD in RR-TB patients were 27.5% (70/255), 27.5% (70/255), 0.4% (1/255) and 2.4% (6/255), respectively. The MICs of LFX, MFX and LZD-susceptible MTB were mainly at 0.25 mg/L, and the MIC of BDQ-susceptible MTB was mainly concentrated at 0.03 mg/L. 25.1% (64/255) of the RR MTB were resistant to both LFX and MFX, and 6 strains were resistant to LFX or MFX, showing incomplete two-way cross resistance. One BDQ-resistant strain and six LZD-resistant strains were detected. The treatment success rate of RR-TB patients was 74.4% (151/203), and there were statistically significant differences in treatment outcomes between resistant and sensitive patients on the LFX-containing treatment regimen (Fisher's exact test, P=0.012). Conclusions: The prevalence of fluoroquinolones (LFX and MFX) resistance in rifampicin-resistant MTB is very serious. LFX and MFX show incomplete bidirectional cross-resistance. BDQ and LZD have the most promising future in the treatment of MDR-TB. Improve drug-resistance testing will help to further improve the success rate of treatment.

[Preliminary study of robot-assisted ankle rehabilitation for children with cerebral palsy].

OBJECTIVE: To propose a kind of robotic ankle-foot rehabilitation system for children with cerebral palsy and to preliminarily verify its feasibility in clinical application. METHODS: A robot assisted ankle-foot rehabilitation system was specially designed and developed for children with cerebral palsy and a preliminary clinical study was conducted in Department of Rehabilitation Medicine, Peking University First Hospital. Modified Tardieu Scale and joint biomechanical properties (ankle plantar flexion resistance torque under different ankle dorsiflexion angles) were measured to analyze the muscle tone and soft tissue compliance of the ankle plantar flexors pre- and post-robotic training intervention. Six children with cerebral palsy (4 girls and 2 boys, mean age: 7 years) were recruited in this study. Each subject received 5 session robotic training and each session included 10-cycle passive stretching and static hold. SPSS 19.0 software was used for data statistical analysis. RESULTS: Both R1 and R2 angles of Modified Tardieu Scale for ankle plantar flexors after training were significantly higher than those before the treatments (Gastrocnemius: PR1=0.003, PR2=0.029; Soleus: PR1=0.002, PR2=0.034). The difference between R2 and R1 was of no statistical difference before and after the training (P=0.067 and P=0.067, respectively). After training, the ankle plantar flexion resistance torque under different dorsiflexion angles (0°, 10°, 20°, 30°) were significantly reduced than those before training (P=0.001, P=0.001, P=0.014, P=0.002, respectively). CONCLUSION: The robot assisted ankle-foot rehabilitation system can improve the contracture and soft tissue compliance of cerebral palsy children's ankle plantar flexors. All the children in the study were well tolerated and interested with the training, easy to accept and cooperate with it. This device may be suitable for application in the rehabilitation of children with cerebral palsy. However, further randomized clinical trials with larger sample size are still needed to verify the long term efficacy of this device.

[Fifth Chinese national consensus report on the management of Helicobacter pylori infection].

The fifth national consensus conference on the management of Helicobacter pylori (H.pylori) infection organized by Chinese Medical Association, Chinese Society of Gastroenterology, H. pylori and Peptic Ulcer Study Group was held at Hangzhou, Zhejiang Province on December 15-16, 2016.More than 80 members of the study group and experts in the field of H. pylori research and gastroenterology attended the meeting.Consensus preparatory group was established to draft the related statements.The quality of evidence and strength of recommendation were evaluated by GRADE system.The Delphi method using an anonymous electronic system was adopted to develop the consensus of relevant statements.Expert advices about the established statements were firstly consulted through the emails.After two rounds of consultation, the preliminary statements of consensus were discussed and modified in the conference item by item.A total of 21 core members voted for the final version, which contained a total of 48 statements and was divided into 6 parts, including indications for H. pylori eradication, diagnosis, treatment, H. pylori and gastric cancer, H. pylori infection in special populations, H. pylori and gastrointestinal microbiota.

[Distribution and drug resistance of nontuberculous Mycobacteria in Beijing].

Objective: To analyze the distribution and drug resistance of nontuberculous mycobacteria(NTM) in Beijing. Methods: Using PCR-fluorescence probe method we identified 1 552 mycobacterial isolates in 2009 and 1 553 mycobacterial isolates in 2013, which were stored by Beijing Research Institute for Tuberculosis Control.All identified NTM strains were confirmed by 16S rRNA gene sequencing, and drug sensitivity testing was performed by using 1% ratio method.SPSS 13.0 was used for statistical analysis. Results: The isolation rate for NTM in 2009 and 2013 was 3.8%(59/1 552), and 4.6%(71/1 553) respectively. A total of 130 NTM strains were identified to 13 species by 16S rRNA gene sequencing, including M. intracellulare strains 39.2%(51/130), M. kansasii strains 37.7%(49/130), M. avium strains 6.9%(9/130), M. abscessus strains 5.4%(7/130), M. fortuitum strains 3.0%(4/130), M. gordonae strains 1.5%(2/130), M. xenopi strains 1.5%(2/130), M. scrofulaceum, M. Phlei, M. smegmatis, M. vaccae, M. neoaurum, M. kumamotonense 1 strain each. For the patients infected with NTM, 87 were male and 43 were female, with an average age of 55 years. The results of drug sensitivity test from 97 strains of NTM showed that isoniazid and p-aminosalicylic acid showed the highest drug resistant rate of 98%(95/97), followed by streptomycin 94.8%(92/97), capreomycin 81.4%(79/97), amikacin 69.1%(67/97), levofloxacin 56.7%(55/97), rifampicin 54.6%(53/97), prothionamide 51.5%(50/97), and ethambutol 50.5%(49/97). Conclusions:Mycobacterium intracellulare and Mycobacterium kansasii were the main strains isolated from patients infected with NTM in Beijing. Patients infected with NTM were mostly males. NTM showed high resistance to anti-tuberculosis drugs.

The PGI-KLF4 pathway regulates self-renewal of glioma stem cells residing in the mesenchymal niches in human gliomas.

Gliomas display cellular hierarchies with self-renewing tumorigenic glioma stem cells (GSCs) at the apex. The GSC niches function as a regulator of GSC maintenance, however, the exact components of GSC niches that mediate this process are still far from fully defined. Here, we showed that glioma cells with aberrant mesenchymal phenotypes constitute a mesenchymal niche for GSCs. Using patient-derived specimens, we demonstrated that the paracrine PGI signaling, initiated by mesenchymal glioma cells, induces the self-renewal and tumorigenic potentials of GSCs through induction of KLF4. Treatment of intracranial orthotopic xenografts with shPGI or shKLF4 leads to less lethal potency. Our data therefore suggest that blockade of the PGI-KLF4 pathway may provide a therapeutic strategy against GSC niches.

Optimization of throughput and desorbent consumption in simulated moving-bed chromatography for paclitaxel purification.

In simulated moving-bed (SMB) applications, throughput and desorbent consumption are two key factors that control process cost. For a given adsorbent volume and product purity requirements, throughput and desorbent consumption depend on desorbent composition, column configuration, column length to diameter ratio, and adsorbent particle size. In this study, these design parameters are systematically examined for paclitaxel purification. The results show that if adsorbent particle size, column dimensions and column configuration are fixed, the higher the product purity required, the lower the throughput. If product purity and yield are fixed, the larger the solute migration speed ratio, the higher the throughput, and the lower the desorbent consumption. If total bed volume and product purities are fixed, the longer the separation zones, the higher the throughput, but the higher the desorbent flow-rate. An intermediate configuration gives the minimum desorbent consumption. If there are no limits on pressure drop or zone flow-rate, the larger the column length to diameter ratio, the smaller the adsorbent particle size, the higher the throughput, and the lower the desorbent consumption. If the maximum zone flow-rate is controlled by the pressure drop limit and not by the standing waves requirement, the longer the columns, the lower the zone flow-rates and the lower the throughput. For 150 microns adsorbent particles and a maximum zone flow-rate of 300 ml/min, a design with optimal throughput and desorbent consumption is found for paclitaxel purification.

Purification of adipoyl-7-amino-3-deacetoxycephalosporanic acid from fermentation broth using stepwise elution with a synergistically adsorbed modulator.

Multicomponent adsorption data of a fermentation broth containing adipoyl-7-amino-3-deacetoxycephalosporanic acid (adipoyl-7-ADCA), a cephalosporin precursor for 7-ADCA, and two key impurities, alpha-hydroxyadipoyl-7-ADCA and alpha-aminoadipoyl-7-ADCA were obtained from batch equilibrium and frontal chromatography tests. Amberlite XAD-1600 was chosen as the resin. A rate model was applied to simulate the chromatograms. An alkaline buffer, which by itself has no affinity for the resin, was used as the eluent. The widely used reversed-phase modulator model is inaccurate in explaining the stepwise elution data. A new model, the induced competition model, has been developed to account for apparent retention of the buffer in the presence of adsorbed species. Close agreement between the simulations and the data was achieved with the new model.

Nonlinear gradient isotherm parameter estimation for proteins with consideration of salt competition and multiple forms.

Salt gradients in ion-exchange chromatography are routinely used to speed separation of proteins and to concentrate products, but systematic optimization of these gradients requires protein equilibrium data as a function of salt concentration. An understanding of conformational changes, aggregation, and salt effects, which include both competition and affinity modulation, is important for equilibrium isotherm parameter estimation. In this study, gradient elution of bovine serum albumin (BSA) in anion exchange was well predicted by a salt-modulated nonlinear isotherm which considers salt competition. The isotherm was able to predict BSA gradient elution from batch equilibrium data. The same isotherm was also able to predict elution for various gradient slopes when fitted to an intermediate slope gradient experiment. If multiple forms due to aggregation or denaturation exist, isotherm parameters are readily averaged in batch experiments because of the long equilibration times. Similarly, gradient experiments yield averaged parameters because the salt gradient tends to merge the closely eluting forms. However, in isocractic elution, if the reaction rate is not rapid enough to give a merged peak, the estimated isotherm parameters are only fair predictors of gradient behavior and vice versa. Slower flow rates in isocratic elution can help reduce the discrepancy by allowing forms to merge through interconversion. As an alternative to determining averaged parameters, consideration of two binding forms, using VERSE-LC, an advanced rate model, gave good agreement with experimental data over the entire range of salt gradient durations.

Ten-year results for Brånemark implants immediately loaded with fixed prostheses at implant placement.

This investigation was initiated to develop a method to provide patients with a fixed provisional prosthesis placed at the time of implant placement. Sixty-three standard 3.75-mm Nobel Biocare implants of varying lengths were placed into mandibular sites in 10 patients and followed for up to 10 years. Twenty-eight implants were immediately loaded at implant placement, providing support for fixed provisional prostheses, while 35 adjacent implants were allowed to heal submerged and stress-free. Following a 3-month healing period, the submerged implants were exposed and definitive reconstruction was accomplished. All 10 prostheses supported by 28 implants placed into immediate function at the time of implant placement were successful during the 3-month healing period. Of these 28 implants placed into immediate function, 4 ultimately failed. Of the 35 submerged implants, all are osseointegrated and in function to date. Life-table analysis demonstrates an overall 10-year survival rate of 93.4% for all implants. The 10-year life-table analysis of survival is 84.7% for immediately loaded implants and 100% for submerged implants. Statistical analysis of the submerged versus immediately loaded implants demonstrates failure rates for immediately loaded implants to be significantly higher (P = .022 by the log rank test). These data demonstrate that although mandibular implants can be successfully placed into immediate function in the short term to support fixed provisional prostheses, long-term prognosis is guarded for those implants placed into immediate function distal to the incisor region.

Osteoid osteoma: clinical and investigative features.

From 1979 to 1988, 15 cases of osteoid osteoma were diagnosed and treated at our hospital. There were 10 males and 5 females, the average age at the time of diagnosis was 17.2 years (from 5 to 54 years). The clinical features were night pain and localized pain in most cases. There was distinct pain relief by salicylate in 58% of the patients with a therapeutic trial. The duration of symptoms before diagnosis averaged 17.9 months (from 1 month to 10 years). Most of the lesions were located in the lower extremities, predominantly in the femur. The hip was a commonly affected site in children and young adults. The X-ray findings in the affected area were classical of the lesion in only 47% of the cases, therefore, preoperative localization of the nidus was aided by either tomography or CT scan. Intraoperative localization by use of an image intensifier and by taking X-rays of the excised specimen has proven to be reliable. All cases underwent en bloc resection of the lesion, and all of the patients were symptom free immediately after the operation, except for one recurrence. A second operation was performed in this case 2 years later and was successful, with pathological confirmation. Fourteen tumors were confirmed by histopathological study, one case could not be confirmed by pathological examination, however the patient obtained complete relief of symptoms postoperatively.

Legg-Calve-Perthes disease: clinical analysis of 57 cases.

The rarity of the Legg-Calve-Perthes disease (LCPD) in Chinese children in Hong Kong has been reported. However, this hip disorder is not uncommon among children in Taiwan between the ages of 3 and 9. Fifty-seven patients with LCPD were observed during a 4-year period. Of these, 47 hips in 43 patients were followed up through a significant course of the disease, with an average period of 38.8 months. The mean age at onset of symptoms was 6.6 years for boys and 7.1 years for girls. Over half of the patients (67%) were older than 6 years of age at onset of the disease. The male: female ratio was 5:1, and the incidence of bilateral involvement was 10%. The majority (85%) belonged to Catterall's group 3 or 4. The skeletal maturity of 17 (68%) these children was delayed an average of 31.8 months. Fifty-three percent of the patients were from families of low socioeconomic status. Delay in diagnosis and presentation with painless limp and stiffness were common. Orthotic management was employed in 15 hips. Surgical containment, either by varus-rotation femoral osteotomy or innominate osteotomy, was achieved in 16 hips. The remaining 16 hips received no treatment. The overall results showed an increase in improvement from 19% to 47% after active treatment of the disease. The chance of satisfactory treatment was reduced considerably when the disease started after the age of 6 years, this was especially obvious in untreated hips. No significant differenced in the healing time between the nonsurgical group and the surgical group was observed.

[Synthesis of 2-formyl (acetyl) substituted quinoline thiosemicarbazones].

A series of 2-formyl (acetyl) substituted quinoline thiosemicarbazones (III, XII, XIII) were prepared in order to evaluate their antimalarial activity. Oxidation of substituted quinolines (IV) with selenium dioxide gave 2-formyl substituted quinolines (V). 2-Acetyl substituted quinoline (IX) was obtained from IV by oxidation, esterification, Claisen condensation and decarboxylation. III1-9 were synthesized by two methods; one was by condensation of 2-formyl (acetyl) substituted quinolines with methyl hydrazinecarbodithioat to form methyl-3-[1-(2-quinolinyl)-alkylidene] hydrazinecarbodithioate (XI), then the S-methyl group of XI was displaced by substituted amines to form the desired substituted thiosemicarbazones. The other was by condensation of 2-formyl (acetyl) substituted quinolines with 4-substituted-3-thiosemicarbazide (X) to afford directly III1-9, III10-12 were obtained by selective reduction of corresponding nitro compounds with stannous chloride and XII as a by-product was obtained by the nonselective reduction of III7 with stannous chloride. 3-Hexyl-4-oxothiazolin-2-yl(2-formyl or acetyl substituted quinoline) hydrazones (XIII1,2) were prepared from III1,4 via cyclization under sodium acetate condition. Eighteen compounds were found to be inactive in mice infected with ANKA strain of Plasmodium berghei.

[Re-discovery of yinzhou chaihu].

This paper deals with the distribution, original plant, course of rise and fall in drug market and quality of Yinzhou Chaihu, which was once regarded as a fine sort of Chinese drug Chaihu (Radix Bupleuri) in ancient times. Further research on this medicinal plant is suggested to facilitate its re-exploitation and utilization.

[Studies on original plant of traditional Chinese drug "bai zhi" (radix Angelicae Dahuricae) and its closely related wild plants. III. Comparison of coumarins of "bai zhi" with those of closely related wild plants].

OBJECTIVE: To provide chemical data for confirming the original plant of traditional Chinese drug "Bai Zhi". METHOD: Coumarins of 4 cultivated breeds of "Bai Zhi" and 3 closely related wild plants, together with other 2 Angelica plants were compared by HPLC. RESULT: According to coumarin patterns, 4 cultivated breeds of "Bai Zhi" and 3 closely related wild plants could be divided into 3 groups: 1. 4 cultivated breeds of "Bai Zhi" ("Chuan Bai Zhi", "Hang Bai Zhi", "Qi Bai Zhi" and "Yu Bai Zhi") and Angelica dahurica var. formosana; 2. A. dahurica; 3. A. porphyrocaulis. CONCLUSION: In point of the coumarin components, A. dahurica var. formosana is closer to traditional Chinese drug "Bai Zhi" than the others.

[Studies on original plant of traditional Chinese drug "bai zhi" (radix Angelicae Dahuricae) and its closely related wild plants. II. Karyological and pollen morphological studies on "bai zhi" and closely related wild plants].

OBJECTIVE: To supplement cytobiological and pollen morphological data for confirming the original plant of traditional Chinese drug "Bai Zhi". METHOD: Karyological study and pollen observation were made on "Bai Zhi" and its closely related wild plants. RESULT: Similarities and differences of "Bai Zhi" and its closely related wild plants were found. CONCLUSION: 1. 4 cultivated breeds of "Bai Zhi", Angelica dahurica, A. dahurica var. formosana, A. porphyrocaulis are really closely related plants. 2. A. dahurica var. formosana is closer to traditional Chinese drug "Bai Zhi" than others.

[Studies on original plant of traditional Chinese drug "bai zhi" (radix Angelicae Dahuricae) and its closely related wild plants. IV. Discussion on original plant and cultivation history of traditional Chinese drug "bai zhi" and evolution of its closely related wild plants].

OBJECTIVE: To confirm the original plant of traditional Chinese drug "Bai Zhi" and to inquire into the cultivation history of "Bai Zhi" and evolution of closely related wild plants of "Bai Zhi". METHOD: Various research results obtained were synthesized and discussed according to historical and current data. RESULT: Obtained research results, historical and current data showed almost no difference. CONCLUSION: 1. Angelica dahurica var. formosana must be the original plant of traditional Chinese drug "Bai Zhi". 2. A. porphyrocaulis should be treated as a variety of A. dahurica, named as A. dahurica var. porphyrocaulis. 3. 4 sorts of Chinese traditional drug "Bai Zhi" (Chuang Bai Zhi, Hang Bai Zhi, Qi Bai Zhi and Yu Bai Zhi) should not be taxonomically distinguished. The history of utilization and cultivation of "Bai Zhi", and the evolutional relation of the closely related wild plants of "Bai Zhi" (A. dahurica, A. dahurica var. formosana, and A. dahurica var. porphyrocaulis) were also discussed.

[Studies on original plant of traditional Chinese drug "bai zhi" (radix Angelicae Dahuricae) and its closely related wild plants. I. Morphological and anatomical studies on "bai zhi" and closely related wild plants].

OBJECTIVE: To supplement morphological and anatomical data for confirming the original plant of traditional Chinese drug "Bai Zhi" (Radix Angelicae Dahuricae). METHOD: Morphologocal observation and anatomical study were made on 4 cultivated breeds and closely related wild plants of "Bai Zhi". RESULT: According to morphological and anatomical characteristics discovered in this paper, 7 samples noted above could be divided into 3 groups: 1. 4 breeds ("Chuan Bai Zhi", "Hang Bai Zhi", "Qi Bai Zhi" and "Yu Bai Zhi") and Angelica dahurica var. formosana; 2. A. dahurica; 3. A. porphyrocaulis. CONCLUSION: In the morphological and anatomical point of view, A. dahurica var. formosana is closer to traditional Chinese drug "Bai Zhi" than others.

Chiral recognition mechanism of acyloin-containing chiral solutes by amylose tris[(S)-α-methylbenzylcarbamate].

Although polysaccharide sorbents have been widely used for chiral separations, the recognition mechanisms have not been fully elucidated. In this study, we focus on one important commercial sorbent, amylose tris[(S)-α-methylbenzylcarbamate] (AS) sorbent. Four solutes containing acyloin, O═C-C-OH, which has a hydroxyl group in the α-position of a carbonyl group, were studied: ethyl lactate (EL), methyl mandelate (MM), benzoin (B), and pantolactone (PL). The observed retention factors (kR and kS) and enantioselectivities (α = kR/ kS) were determined in n-hexane and in hexane-isopropanol (IPA) solutions. Infrared (IR) spectroscopy and density functional theory (DFT) simulations of the interactions of these solutes with the side chains of the polymer led to a general hypothesis for the chiral recognition mechanism for these solutes: A strong H-bond forms as the primary (or "leading") nonenantioselective interaction (or "anchor" point) between the solute OH group of each enantiomer and the sorbent C═O group. A weaker H-bond forms preferably for the R enantiomer between the solute C═O groups and the sorbent NH groups. The S enantiomer is prevented from forming such a bond for steric restrictions. A third interaction might involve the O groups of the phenyl groups of the solutes. IR spectroscopy shows evidence of an intramolecular H-bond for all four solutes. The retention factors were found to increase with increasing strength of the intermolecular H-bond and with decreasing strength of the intramolecular H-bond. The enantioselectivities were found to correlate with the molecular rigidity or flexibility, as determined from the distribution of the torsion angles of the acyloin group. The enantioselectivity was higher for the more rigid molecules. Simulations of left-handed AS with 200 n-hexane molecules indicated no effect of hexane on the H-bonds in AS. Monte Carlo (MC) and molecular dynamics (MD) "docking" simulations of AS with these solutes revealed certain chiral cavities that can lead to chiral discrimination. The results support the proposed mechanism.