[Transoral robotic thyroidectomy via vestibular approach: a retrospective study of 107 cases in a single center].

Objective: To investigate the short-term outcome of transoral robotic thyroidectomy. Methods: This is a retrospective case series study. The clinicopathologic characteristics and postoperative results of 107 patients who underwent transoral robotic thyroidectomies in the Department of Thyroid and Breast Surgery of the 960th Hospital of People's Liberation Army from May 2020 to August 2023 were retrospectively analyzed. There were 12 males and 95 females, with an age of (31.8±9.4) years (range: 11 to 55 years), including 20 benign tumors and 87 thyroid papillary carcinoma. Postoperative follow-up was carried out through returning visit and telephone, mainly to observe the recovery of postoperative complications, cosmetic effects and recurrence results. Results: All transoral robotic thyroidectomy was successfully completed without conversion to open surgery. The tumor size of thyroid papillary carcinoma patients was (5.6±2.7) mm (range: 2 to 15 mm). Furthermore, central cervical lymph node metastasis was found in 45 cases. The number of central cervical lymph nodes retrieved and metastasized (M(IQR)) were 11 (8) (range: 3 to 26) and 1 (3) (range: 0 to 13), respectively. There was no recurrent laryngeal nerve injury and permanent hypoparathyroidism. The transient hypoparathyroidism after surgery was 8 cases. Other complications occurred as follows: postoperative infection (n=1), left submandibular perforation (n=1), skin scald (n=1), and perioral numbness (n=1), oral tear (n=2). The postoperative stay was 6 (2) days (range: 3 to 11 days). No local lymph node recurrence or metastasis occurred after a follow-up of (22.6±10.0) months (range: 1.0 to 37.4 months). All patients were satisfied with the postoperative cosmetic results, the aesthetic effect score was 9.3 (0.2) (range: 8.4 to 9.6) one month after surgery. Conclusion: For highly screened patients with early thyroid cancer, experienced surgeons can perform a transoral robotic thyroidectomy that has excellent cosmetic results.

[Clinical and imaging features of infective sacroiliitis in children].

Objective: To summarize the clinical, radiological characteristics, and prognosis of infectious sacroiliitis in children. Methods: A case-control study was conducted, including 12 cases of infectious sacroiliitis diagnosed in the Rheumatology and Immunology Department of the Children's Hospital affiliated with the Capital Institute of Pediatrics from June 2018 to June 2023. These cases comprised the case group. Concurrently, 28 cases of pediatric idiopathic arthritis involving the sacroiliac joint in the same department served as the control group. Basic patient information, clinical features, laboratory parameters, and clinical treatment outcomes for both groups were collected and analyzed. Independent sample t-tests and chi-squared tests were used for inter-group comparisons. Results: Among the 12 cases in the case group, there were 5 males and 7 females, with a disease duration of 0.8 (0.5, 1.2) months. Nine patients presented with fever, and 1 patient had limping gait. Human leukocyte antigen (HLA)-B27 positivity was observed in 1 case, and there was no family history of ankylosing spondylitis. In the control group of 28 cases, there were 19 males and 9 females, with a disease duration of 7.0 (3.0, 17.0) months. One patient (4%) had fever, and 14 cases (50%) exhibited limping gait. HLA-B27 positivity was found in 18 cases (64%), and 18 cases (64%) had a family history of ankylosing spondylitis. The case group had higher white blood cell count (WBC), neutrophil ratio, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, as well as a higher proportion of unilateral involvement on magnetic resonance imaging and bone destruction on CT compared to the control group ((11.1±6.2)×109 vs. (7.3±2.3)×109/L, 0.64±0.10 vs. 0.55±0.12, 72 (34, 86) vs. 18 (5, 41) mm/1 h, 24.6 (10.1, 67.3) mg/L vs. 3.6 (0.8, 15.0) mg/L, 11/12 vs. 36% (10/28), 9/12 vs. 11% (3/28), t=2.90, 3.07, Z=-2.94, -3.28, χ2=10.55, 16.53, all P<0.05). Conclusions: Pediatric infectious sacroiliitis often presents as unilateral involvement with a short disease history. Elevated WBC, CRP, and ESR, as well as a high rate of bone destruction, are also common characteristics.

[Development and application syndromic surveillance and early warning system in border area in Yunnan Province].

Objective: To establish a dynamic syndromic surveillance system in the border areas of Yunnan Province based on information technology, evaluate its effectiveness and timeliness in the response to common communicable disease epidemics and improve the communicable disease prevention and control in border areas. Methods: Three border counties were selected for full coverage as study areas, and dynamic surveillance for 14 symptoms and 6 syndromes were conducted in medical institutions, the daily collection of information about students' school absence in primary schools and febrile illness in inbound people at border ports were conducted in these counties from January 2016 to February 2018 to establish an early warning system based on mobile phone and computer platform for a field experimental study. Results: With syndromes of rash, influenza-like illness and the numbers of primary school absence, the most common communicable disease events, such as hand foot and mouth disease, influenza and chickenpox, can be identified 1-5 days in advance by using EARS-3C and Kulldorff time-space scanning models with high sensitivity and specificity. The system is easy to use with strong security and feasibility. All the information and the warning alerts are released in the form of interactive charts and visual maps, which can facilitate the timely response. Conclusions: This system is highly effective and easy to operate in the detection of possible outbreaks of common communicable diseases in border areas in real time, so the timely and effective intervention can be conducted to reduce the risk of local and cross-border communicable disease outbreaks. It has practical application value.

Lactobacillus coryniformis subsp. torquens inhibits bone loss in obese mice via modification of the gut microbiota.

High-fat diet (HFD)-induced obesity results in bone loss associated with an imbalanced gut microbiota and altered immune status. Probiotics are live microorganisms that are beneficial to the host and are important in maintaining bone health and gut homeostasis. In this study, the probiotic Lactobacillus coryniformis subsp. torquens (T3L) was isolated from traditional yak milk cheese produced in Lhasa and showed distinct acid and bile salt resistance as potential probiotics. Our data indicated that T3L not only reversed HFD-induced gut dysbiosis, as indicated by decreased Firmicutes-to-Bacteroidetes ratios but also reduced bone loss. The anti-obesity, microbiome-modulating, and bone-protective effects were transmissible via horizontal faeces transfer from T3L-treated mice to HFD-fed mice. The protective effects of T3L on bone mass were associated with regulatory T (Treg) cell-mediated inhibition of osteoclast differentiation. Our data indicate that T3L is a regulator of the gut microbiota and bone homeostasis in an animal model.

[A retrospective comparative study between robotic thyroidectomy through transoral vestibular approach and bilateral breast-axillary approach].

Objective: To compare the surgical outcome of robotic thyroidectomy through transoral approach and the bilateral breast-axillary approach. Methods: Retrospective analysis was made on the clinical data of patients who performed transoral robotic thyroidectomy (TORT group) or bilateral breast-axillary approach (BABA group) in the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army from July 2020 to May 2022. Both groups received lobectomy with lymph node dissection of the central region. A total of 100 cases were included in the study, including 48 cases in the TORT group and 52 cases in the BABA group. The propensity score matching method was used for 1∶1 matching of patients between the 2 groups, with a match tolerance of 0.03. There were 31 patients in each group successfully matched. In the TORT group, there were 5 males and 26 females, aged (33.2±7.9) years (range: 21 to 53 years). While there were 4 males and 27 females in the BABA group, aged (34.6±9.2) years (range: 19 to 58 years). The t test, Mann-Whitney U test, χ2 test or Fisher exact test were used to compare the clinical efficacy between the two groups. Results: All the patients successfully completed robotic thyroid surgery without conversion to open surgery. Compared with BABA group, the TORT group had longer operation time ((211.3±57.2) minutes vs. (126.2±37.8) minutes, t=6.915, P<0.01), shorter drainage tube retention time ((5.4±1.0) days vs. (6.4±1.2) days, t=-3.544, P=0.001), shorter total hospital stay ((6.6±1.2) days vs. (7.4±1.3) days, t=-2.353, P=0.022), and higher cosmetic score (9.46±0.25 vs. 9.27±0.26, t=2.925, P=0.005). There was no significant difference between the two groups in the number of lymph nodes dissection, metastasis in the central compartment, and the incidence of postoperative complications (all P>0.05). Conclusions: Compared with the bilateral breast-axillary approach, the transoral vestibular approach of robotic thyroidectomy is also safe and effective. It shows similar surgical results to the bilateral breast-axillary approach in strictly selected patients, but the postoperative recovery speed is much faster, and the hospital stay is shorter. Transoral robotic thyroidectomy is a more recommended surgical method for patients with high aesthetic demand.

[Analysis of glucose changes in adults with type 1 diabetes mellitus within 1 year after using mobile APP decision support system].

Objective: To analyze the changes in glucose after using a decision support system (DSS) of a smartphone mobile application (APP) in adults with type 1 diabetes mellitus (T1DM). Methods: In the intervention study, the data (including general information at the time of registration) of adult T1DM patients enrolled in the Chinese T1DM Registration Management Project and registered with TangTangQuan® APP were collected. Within 1 year after registration, fasting blood glucose, pre-prandial and postprandial blood glucose at the three meals, blood glucose before bedtime and in nocturnal time were collected every 3 months. Frequencies of total recorded glucose values and proportion of different ranges of glycemia were also collected and analyzed, including the range between 3.9-7.8 mmol/L (Euglycemia), ranged below 3.9 mmol/L (Hypoglycemia) and range above 13.9 mmol/L (hyperglycemia). The patients were divided into 3 groups according to the daily use frequency of DSS (Low/Moderate/High frequency groups). The changes in point blood glucose, the proportion of hyperglycemia and hypoglycemia over time were compared among different groups, as well as the baseline characteristics and glucose characteristics of patients. Results: A total of 629 eligible T1DM patients were included, including 216 (34.3%) males and 413 (65.7%) females, aged (31.5±10.8) years, and disease duration [M(Q1, Q3)] of 1.2 (0.1, 7.4) years. There were 239, 189 and 201 patients in the low, moderate and high frequency groups, respectively. Significant differences were observed among the three groups in all timepoints of self-monitoring blood glucose except for the glucose before bedtime from 10 to 12 months after registration (all P values<0.05), and the glucose level at each point in the high frequency group was lower than that in the other two groups. In the first three months after registration, there was no difference in the proportion of hypoglycemia among the three groups (P>0.05). However, from 10 to 12 months after registration, the proportion [M(Q1, Q3)] of hypoglycemia [3.34% (0.85%, 7.40%), 3.00% (0.78%, 6.17%), 1.81% (0.37%, 4.69%)] (P=0.022) between groups (from low to high frequency groups) and hyperglycemia [4.04% (0, 12.16%), 1.88% (0, 7.80%), 0.81% (0, 3.87%)] (P=0.001) were significantly different. Conclusions: The DSS function of mobile APP is helpful to the glucose management of adult patients with T1DM within 1 year after registration. The average blood glucose in adults with T1DM decreased, and the proportions of hyperglycemia and hypoglycemia were also reduced.

[Clinical analysis of 5 cases of systemic juvenile idiopathic arthritis with coronary artery dilatation].

Objective: To investigate the clinical characteristics of systemic juvenile idiopathic arthritis combined with coronary artery dilatation. Methods: A retrospective analysis was performed on the clinical data, including clinical manifestations, blood routine, inflammatory factors, echocardiography, vascular ultrasound and CT angiography, treatment and outcomes, etc, of 5 cases with systemic juvenile idiopathic arthritis combined with coronary artery dilation admitted to Department of Rheumatology in the affiliated Children's Hospital of Capital Institute of Pediatrics from May 2019 to June 2021. Results: There were 2 males and 3 females among 5 cases. The onset age ranged from 7 months to 4 years 7 months.The diagnostic time ranged from 1.5 months to 3.0 months.Four cases were diagnosed as atypical Kawasaki disease. Three cases showed unilateral coronary artery dilation.Two cases showed bilateral coronary artery dilation.Four cases developed multiple organ injuries.Three cases developed macrophage activation syndrome.Three cases developed lung injury.Two cases developed pericardial effusion.One case developed pulmonary hypertension.As for treatment, 3 cases treated with methylprednisolone pulse therapy and methotrexate combined with cyclosporine, improved after the final application of biological agents, and have stopped prednisone. The other 2 cases were treated with adequate oral prednisone and gradually reduced, and methotrexate was added at the same time, 1 case relapsed in the process of reduction. No other vascular involvement was found in 5 cases. Coronary artery dilation recovered completely after 1 to 3 months of treatment. Conclusions: Systemic juvenile idiopathic arthritis combined with coronary artery dilatation has the clinical characteristics of small onset age, long diagnostic time, prone to multiple organ injuries. Corticosteroids and conventional immunosuppressive agents are not sensitive, and biological agents should be used as soon as possible.The prognosis of coronary artery dilation is good after timely treatment.

[Preliminary application of transoral robotic thyroidectomy: experience from an initial 30 cases].

Objective: To examine the surgical outcome of transoral robotic thyroidectomy. Methods: Clinic data of total 30 cases of transoral robotic thyroidectomy at the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army from May 2020 to December 2020 were analyzed retrospectively. There were 3 males and 27 females, aged (31.5±11.0) years (range: 17 to 55 years), including 6 cases of benign tumor and 24 cases of malignant cancer (all papillary thyroid carcinoma). An inverted U-shaped incision 1.5 cm in length was made over the end of the frenulum of the lower lip. A wide subplatysmal space was created by bluntly passing with a vascular tunneller (8 mm diameter), and a 12 mm trocar was inserted through the lip incision for the camera port. Lateral oral mucosal incisions 8 mm in length were made near both lateral labial commissures, 8 mm robot trocars were inserted through the incisions. An 5 mm trocar was inserted through an incision made along the patient's right axillary fold into the subplatysmal working space and was connected with 5 mm ProGrasp for counter traction during the operation and for later drain insertion. Numerical scoring system (NSS) was used to assess cosmetic effect 1 month post-operation. Results: All the 30 transoral robotic thyroidectomies was successful, no case conversed to open operation. Postoperative hospital stay was (6.3±1.2) days (range: 4 to 10 days). The tumor size of thyroid cancers was (5.3±3.0) mm (range: 2 to 15 mm). Lymph node metastasis was observed in 12 cases. The retrieved central lymph node number was 10.5±4.4 (range: 4 to 20), while the central metastatic lymph node number was 2(2) (range: 1 to 11). Postoperative transient hypoparathyroidism occurred in 2 cases. Permanent hypoparathyroidism and vocal cord palsy didn't occur. Other surgical complications included hematoma, surgical site infection and perforation of chin flap, retrospectively in 1 case. Local regional lymph node recurrence wasn't developed during 1 to 7 months follow-up. All patients were satisfied with the postoperative cosmetic outcomes,NSS was 9.4±0.8 (range: 8.7 to 9.6). Conclusion: Transoral robotic thyroidectomy is safe and effective, suitable for early thyroid cancers without lateral lymph node metastasis, and has superior cosmetic results when the patients are selected carefully.

Identification of Shiga-Toxin-Producing Shigella Infections in Travel and Non-Travel Related Cases in Alberta, Canada.

It has long been accepted that Shiga toxin (Stx) only exists in Shigella dysenteriae serotype 1. However, in recent decades, the presence of Shiga toxin genes (stx) in other Shigella spp. have been reported. We screened 366 Shigella flexneri strains from Alberta, Canada (2003 to 2016) for stx and 26 positive strains were identified. These isolates are highly related with the majority originating from the Dominican Republic and three isolates with Haiti origin. Both phylogenetic and spanning tree analysis of the 26 Alberta and 29 stx positive S. flexneri originating from the U.S., France, Canada (Quebec) and Haiti suggests that there are geographic specific distribution patterns (Haiti and Dominican Republic clades). This study provides the first comprehensive whole genome based phylogenetic analysis of stx positive S. flexneri strains as well as their global transmission, which signify the public health risks of global spreading of these strains.

[Outcomes of 1 000 cases of robotic thyroidectomy by bilateral axillo-breast approach: a retrospective study in a single center].

Objective: To examine the surgical outcome, completeness and safety of robotic thyroidectomy by bilateral axillo-breast approach (BABA). Methods: From February 2014 to May 2019, 1 000 cases of robotic thyroidectomy via BABA at the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army were performed. The clinicopathologic characteristics, operation times, perioperative complications, and oncologic outcomes of patients underwent robotic thyroidectomy were collected and reviewed retrospectively. There were 216 males and 784 females, aging (42.3±11.5) years (range: 7 to 75 years). There were 270 cases with benign tumors, and 730 cases with malignant cancers (the tumor diameter was (7.9±6.7) mm (range: 0.1 to 60.0 mm)). Results: There were 999 patients received robotic thyroidectomy using BABA approach successfully, while only 1 case conversed to open operation. The postoperative hospital stay was (7.5±2.5) days (range: 2 to 30 days). Among the 730 patients with thyroid cancers, 725 cases (99.3%) were papillary thyroid carcinoma, 579(79.3%) cases were with papillary thyroid microcarcinoma. Lymph node metastasis was observed in 371(50.8%) cases. The retrieved central lymph node number was 11.2±6.1 (range: 1 to 44),and the retrieved lateral lymph node number was 14.0±8.8 (range: 1 to 52). Postoperative transient hypoparathyroidism and vocal cord palsy occurred in 247(24.70%) and 56(5.60%) cases. Both of permanent hypoparathyroidism and vocal cord palsy occurred in 2 (0.20%) cases. Other surgical complications included chyle leakage (6.1%, 28/460), trachea injury (0.40%, 4/1 000), carotid artery injury (0.10%, 1/1 000). Local regional lymph node recurrence was developed in 4 patients. All patients were satisfied with the postoperative cosmetic outcomes. Conclusions: Robotic thyroidectomy by BABA is safe and effective, suitable for large benign tumors and early thyroid cancers with central or lateral lymph node metastasis. It could obtain superior cosmetic results.

[A predictive model based on risk factors for early mortality in patients with newly diagnosed multiple myeloma].

Objective: To investigate risk factors for early mortality (EM) in patients with newly diagnosed multiple myeloma (NDMM) and to build an EM-predictive model. Methods: In a cohort of 275 patients with NDMM, risk factors for EM at 6, 12, and 24 months after diagnosis (EM6, EM12, and EM24, respectively) were determined to establish a model to predict EM. Results: The rates of EM6, EM12, and EM24 were 5.5% , 12.7% , and 30.2% , respectively. The most common cause for EM was disease progression/relapse, accounting for 60.0% , 77.1% , and 84.3% of EM6, EM12, and EM24, respectively. EM6 was associated with corrected serum calcium >2.75 mmol/L and platelet count <100×10(9)/L, whereas risk factors for EM12 included age >75 years, ISS Ⅲ, R-ISS Ⅲ, corrected serum calcium >2.75 mmol/L, serum creatinine >177 µmol/L, platelet count <100×10(9)/L, and bone marrow plasma cell ratio ≥ 60% . In addition to the risk factors for EM12, EM24 was also associated with male sex and 1q21 gain. By multivariate analysis, age >75 years, platelet count <100×10(9)/L, and 1q21 gain were independent risk factors for EM24 but there were no independent risk factors significantly associated with EM6 and EM12. Using a scoring system including these three risk factors, a Cox model for EM24 was generated to distinguish patients with low (score<3) and high (score ≥ 3) risk. The sensitivity and specificity of the model were 20.7% and 99.2% , respectively. Further, an internal validation performed in a cohort of 183 patients with NDMM revealed that the probability of EM24 in high-risk patients was 26 times higher than that in low-risk patients. Moreover, this model was also able to predict overall survival. The median overall survival of patients with scores of 0, 1, 2, 3, 4, and 5 were 59, 41, 22, 17.5, and 16 months, respectively. Conclusion: In the study cohort, the EM6, EM12, and EM24 rates were 5.5% , 12.7% , and 30.2% , respectively, and disease progression or relapse were main causes of EM. An EM24-predictive model built on three independent risk factors for EM24 (age>75 years, platelet count<100×10(9)/L, and 1q21 gain) might predict EM risk and overall survival.

[Complications of Da Vinci robot thyroid surgery by bilateral axillo-breast approach].

Objective: To evaluate the complications of Da Vinci robotic thyroid surgery by bilateral axillo-breast approach. Methods: A retrospective analysis of complications was conducted on 1, 198 cases of Da Vinci robotic thyroid surgery by bilateral axillo-breast approach of the 960 th Hospital of the People's Liberation Army from February 2014 to March 2020. There were 263 men and 935 women, age ranged from 9 to 68 years old, and included 288 benign lesions and 910 malignancies according to preoperative imaging examination, FNAC, and intraoperative frozen pathology. Results: Surgical complications occurred in 187 (15.61%) patients, including 10 cases of temporary larynx nerve injury (0.83%), 1 case of permanent larynx nerve injury (0.08%), and 152 cases of temporary hypoparathyroidism (12.69%), no permanent hypoparathyroidism, 1 case of hypoglossal injury (0.08%), 2 cases of facial nerve jaw branch damage (0.17%), 2 cases of trachea injury (0.17%), no esophagus damage, 5 cases of celiac leakage (0.42%), 3 cases of neck skin adhesion (0.25%), 2 cases of subdermal bleeding (0.17%), 2 cases of skin burns (0.17%), 5 cases of hematoma (0.42%), 1 case of cephalic artery rupture (0.08%), 1 case of jugular vein rupture (0.08%), no tumor cultivation, no arm plex nerve, accessory nerve or phrenic nerve damage. Conclusion: Da Vinci robot thyroid surgery by bilateral axillo-breast approach is safe, with less severe complications.

[Molecular regulatory mechanisms of hypoxia-inducible factor and interventional effect of Chinese herbal medicine].

Hypoxia-inducible factors(HIFs)are the key transcription factors that sense and regulate cellular oxygen concentration in vivo. HIF-1 is composed of 2 subunits,α and ß,in which,the molecular regulatory mechanism of HIF-1α involves the main processes of its degradation and activation. The degradation of HIF-1α is regulated by oxygen-dependent pathways,including "von hippel-lindau protein(pVHL)-dependent pathway" and "pVHL-independent pathway". The activation of HIF-1α is regulated by oxygen-independent pathways,including mammalian target of rapamycin(mTOR)/eukaryotic initiation factor 4 E-binding protein 1(4 EBP1)/HIF-1α pathway,phosphatidylinositol 3-kinase(PI3 K)/proteirrserinc-threonine kinases(Akt)/HIF-1α pathway and silent information regulator1(Sirt1)/HIF-1α pathway. In recent years,based on the molecular regulatory mechanism of HIFs,Roxadustat,a new drug for the treatment of renal anemia has been developed. Besides, some macromolecular substances with similar pharmacological effect to HIFs have been found in the extracts from Chinese herbal medicine(CHM),such as emodin,notoginseng triterpenes,honokiol and clematichinenoside. These natural macromolecular substances play the regulatory roles in inflammatory response,epigenetic modification and auto-phagy. It is worth noting that,for common hypoxic-related diseases including diabetic kidney disease,HIFs-mediated "pyroptosis" may be a new target of CHMs for clearing dampness and heat and its representative classical prescriptions(Ermiao Pills)in treating inflammatory injury in cells and tissues.

The association between sympatho-vagal balance and central blood pressures.

PURPOSE: High central blood pressure is more predictive of cardiovascular disease (CVD) versus high peripheral blood pressure. Measures of central pressures (CPs) include, central systolic blood pressure (CSBP) and central diastolic blood pressure. Measures of central pressures augmentation (CPsA) include augmentation pressure (AP) and the augmentation index @ 75 beats·min-1 (AIx@75). Increased sympathetic tone (ST) is also associated with CVD. The low to high frequency ratio (LF/HF) is often used to determine sympatho-vagal balance. Given the association between ST, CPs, CPsA and CVD there is a need to understand the association between these predictors of CVD. The aims of this study were to examine the association between the LF/HF ratio, CPs, and CPsA in men and women collectively and based on gender. METHODS: We measured the LF/HF ratio, CSBP, AP, and AIx@75 in 102 participants (41F/61M). The LF/HF ratio was determined via power spectral density analysis. CSBP, AP, and AIx@75 were determined via applanation tonometry. RESULTS: The LF/HF ratio was inversely associated with AP (r = -0.26) and AIx @75 (r = -0.29) in the combined group of men and women. The LF/HF ratio was inversely associated with CSBP (r = -0.27), AP (r = -0.28), and AIx@75 (r = -0.32) in men, but not in women. CONCLUSION: There is an inverse association between the LF/HF ratio, AP, and AIx@75 in men and women combined. The association between the LF/HF ratio, CSBP, AP, and AIx@75, differs based on gender.

3-phenyllactic acid production by free-whole-cells of Lactobacillus crustorum in batch and continuous fermentation systems.

AIM: 3-Phenyllactic acid (3-PLA) has been widely used in food and material industries. Three Lactobacillus crustorum strains have shown greater 3-PLA production ability in our previous study. The objectives of this study were to further improve 3-PLA yields in batch and continuous fermentation systems using of free-whole-cells of the three L. crustorum strains. MATERIALS AND RESULTS: The fermentation conditions of free-whole-cells of the three L. crustorum strains for 3-PLA production were optimized. Among these strains, L. crustorum NWAFU 1078 showed excellent reusability and significantly (P < 0·05) greater 3-PLA production ability than the other strains after 10th recycle. The strain possesses three l-lactate dehydrogenase and three d-lactate dehydrogenase catalysing 3-PLA production from phenylpyruvic acid (PPA). Under the optimal conditions, the strain produced 15·2 mmol l-1 3-PLA (76% PPA conversion rate) in a batch fermentation system and 6·5 mmol l-1  h-1 3-PLA (55% PPA conversion rate) in a continuous fermentation system using a 0·6 dilution rate. CONCLUSIONS: Free-whole-cells of L. crustorum NWAFU 1078 showed excellent reusability and higher 3-PLA yields under optimal biotransformation conditions in both batch and continuous fermentation systems. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides the possibility to use the free-whole-cells of L. crustorum NWAFU 1078 as a biocatalyst for effective production of 3-PLA.

[Adverse effects of double-hit combining ISS-â ¢ stage and 1q gain or del (17p) on prognosis of patients with newly diagnosed multiple myeloma].

Objective: To evaluate the prognostic significance of combining ISS-Ⅲ and high risk cytogenetic abnormalities [HRCAs, including 1q gain/amplification and del (17p) ] in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The clinical characteristics and relevant variables were retrospectively analyzed in a total of 270 NDMM patients diagnosed between November 2009 and May 2018. ISS-Ⅲ stage and HRCAs [detected by FISH, including 1q gain/amplification and del (17p) ] were defined as risk factors (hit) . Based to the number of hit per case, these patients were divided into four groups carrying 0 to 3 risk factors, respectively. Progress-free survival (PFS) and overall survival (OS) were then analyzed using the Kaplan-Meier estimator. Results: Patients who carried single hit (n=120, 44.4%) had shorter median PFS (23.0 vs 28.9 months; P>0.05) and OS (42.3 vs 53.7 months; P>0.05) than those with no risk factors (n=66, 24.4%) . Of note, the outcome of patients who had two or more risk factors (double/triple, n=84, 31.1%) was much worse than those with either no or one risk factor, indicated by significantly reduced median PFS (14.5 months; HR=1.584, 95%CI 1.082-2.319; P=0.003 for double/triple vs single hit) and OS (18.4 months, HR=2.299, 95%CI 1.485-3.560; P<0.001 for double/triple vs single hit) . Strikingly, patients who had three risk factor (triple hit, n=5, 1.9%) displayed the poorest survival with extraordinarily shorter PFS (0.9-15.1 months) and OS (0.9-18.9 months) compared to those carrying two risk factors (double hit) . Analogous results were obtained when different combinations of ISS stages and HRCAs were analyzed. Conclusion: These results suggest a potential but rather important role of combining multiple (e.g. double or triple) adverse factors determined via the routine ISS staging and FISH detection of cytogenetic abnormalities in risk stratification and prognostic prediction, which might be helpful to identify high risk patients more precisely at diagnosis. It also raised a possibility that a small group of ISS-Ⅲ patients carrying both 1q gain/amplification and del (17p) might represent an "extremely-high risk" subset of MM.

Structure and mode of action of a novel antibacterial peptide from the blood of Andrias davidianus.

Andrias davidianus is widely recognized in traditional medicine as a cure-all to treat a plethora of ailments. In a previous study, a novel antibacterial peptide named andricin B was isolated from A. davidianus blood. In this study, we investigated andricin B structure and its mode of action. Circular dichroism spectra suggested that andricin B adopts a random coil state in aqueous solution and a more rigid conformation in the presence of bacteria. Moreover propidium iodide/fluorescein diacetate double staining indicated that bacteria treated with andricin B were not immediately eliminated. Rather, there is a gradual bacterial death, followed by a sublethal stage. Scanning electronic microscope imaging indicates that andricin B might form pores on cell membranes, leading to the release of cytoplasmic contents. These results were consistent with flow cytometry analysis. Furthermore, Fourier transform infrared spectroscopy suggests that andricin B induces changes in the chemical properties in the areas surrounding these "pores" on the cell membranes. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study suggested the new perspectives about the mode of action of antimicrobial peptide (AMP) active against sensitive bacteria. The AMP was able to be in a random coiled state in aqueous solution but to change to a more rigid one in the presence of sensitive bacteria. Exposure to AMP might not lead to immediate death of treated bacteria, rather bacteria concentration decreased gradually flattening at a sublethal stage. These findings will help people to understand better how the AMPs activate against sensitive bacteria.

[Prognostic analysis of 182 newly diagnosed multiple myeloma patients with high risk cytogenetic abnormalities].

Objectives: To evaluate the clinical characteristics and prognosis of high risk cytogenetic abnormalities (HRCA) and various combinations of cytogenetic abnormality in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: This retrospective study collected 182 NDMM patients in the First Affiliated Hospital of Jilin University between Nov. 2009 and May 2018. HRCA included 1q+, del (17p) , t (4;14) , and t (14;16) detected by FISH, and non-HRCA included del (13q) , t (11;14) detected by FISH. The clinical characteristics among three groups, including cases who carrying a single HRCA, 1 HRCA in combination with non-HRCA and cases carrying two or more HRCAs (double/triple-hit) were observed. Kaplan-Meier curve was used to analyze both progression-free survival (PFS) and overall survival (OS) for the three groups. Results: The survivals of patients with 1 HRCA in combination with non-HRCA were similar to those with two or more HRCAs (double/triple-hit) , the median PFS (mPFS) was 19.1 m vs 12.1 m (P=0.248) and median OS (mOS) was 29.6 m vs 29.3 m (P=0.774) . Furthermore, the prognosis of these two groups were both inferior to patients with a single HRCA, respectively. (mPFS: 32.2 m, P=0.040, P=0.001; mOS: 42.3 m, P=0.021, P=0.041) . Strikingly, both the mPFS and the mOS of patients with 1 HRCA in combination with non-HRCA (regardless of high risk or not) were significantly shorter than that of cases with a single HRCA (mPFS: 15.1 m vs 32.2 m, HR=2.126, 95%CI 1.176-3.843, P=0.005; mOS: 29.3 m vs 42.3 m, HR=1.442, 95%CI 0.705-2.950, P=0.011) . Conclusion: It is of prognostic significance value for detecting double/triple-hit based on FISH cytogenetics in NDMM.

Case reports: novel TUBG1 mutations with milder neurodevelopmental presentations.

BACKGROUND: Tubulinopathies result from mutations in tubulin genes, including TUBG1, responsible for cell microtubules, are characterized by brain development abnormalities, microcephaly, early-onset epilepsy, and motor impairment. Only eleven patients with TUBG1 mutations have been previously described in literature to our knowledge. Here we present two new patients with novel de novo TUBG1 mutations and review other cases in the literature. CASE PRESENTATIONS: Both patients have microcephaly and intellectual disability. Patient B further fits a more typical presentation, with well-controlled epilepsy and mild hypertonia, whereas Patient A's presentation is much milder without these other features. CONCLUSION: This report expands the spectrum of TUBG1 mutation manifestations, suggesting the possibility of less severe phenotypes for patients and families, and influencing genetic counselling strategies.

[LIG4 syndrome: a report of four cases and literature review].

Objective: To analyze clinical, immunological and genetic characteristics of 4 cases of LIG4 syndrome. Methods: We retrospectively analyzed the clinical data of 4 patients from 3 families with LIG4 syndrome who were admitted to Children's Hospital of the Capital Institute of Pediatrics from June 2017 to May 2018, and reviewed related articles, the clinical, immunological and genetic characteristics of LIG4 syndrome were summarized and analyzed. Results: Those 4 cases (P1 to P4), including 2 males and 2 females, had an average age of 1.5 years. All of them presented with special facial features, such as microcephaly, beak-like-nose, and receding forehead. Three of them presented with delayed physical development. P3 suffered from mental retardation and P4 had feeding difficulty. BCG scars were repeatedly ruptured in 3 cases, 4 cases had pneumonia, 1 case had EB virus infection, 2 cases had cytomegalovirus infection, 1 case had fungal infection, and 1 case had chronic diarrhea. Blood routine tests showed decreased neutrophil and lymphocyte counts. Immunoassay showed decreased absolute count of CD4(+)T lymphocyte and B lymphocyte, with normal CD8(+)T cells. P1, P2 presented with decreased immunoglobulin. All of those patients had LIG4 gene complex heterozygous mutations, of whom one had missense mutation had mild clinical phenotype and another three cases had frameshift mutation presented with severe clinical phenotype. One patient underwent hematopoietic stem cell transplantation, and has established normal immune function. He did not have recurrent infection during one year follow-up period. The other 3 patients had preventive anti-infection treatment and received regular human immunoglobulin infusion, but they still had recurrent infection. In literature review, 67 articles were retrieved, totally 37 case were reported, showing special faces and recurrent infection as characteristic presentation of this disease. Conclusions: The typical manifestations of LIG4 syndrome are microcephaly, special facial features and repeated infection. The average age at diagnosis of LIG4 syndrome was more than one year old. If a patient presented with microcephaly, BCG scar infection and leukopenia, LIG4 syndrome should be considered. Immunoglobulin is decreased at different degrees, and CD4(+) and CD19(+) lymphocyte counts always decrease, Naive T and B cells decrease more prominently, and CD8(+)T cells were normal in patients with typical LIG4 syndrome. It is effective to reconstruction of immune system with bone marrow transplantation in LIG4 syndrome patients.