The phosphotransferase system gene ptsH affects persister formation in Klebsiella pneumoniae by regulating cyclic adenosine monophosphate levels.

Klebsiella pneumoniae is one of the most common opportunistic pathogens causing hospital- and community-acquired infections. Antibiotic resistance in K. pneumoniae has emerged as a major clinical and public health threat. Persisters are specific antibiotic-tolerant bacterial cells. Studies on the mechanism underlying their formation mechanism and growth status are scarce. Therefore, it is urgent to explore the key genes and signalling pathways involved in the formation and recovery process of K. pneumoniae persisters to enhance the understanding and develop relevant treatment strategies. In this study, we treated K. pneumoniae with a lethal concentration of levofloxacin. It resulted in a distinct plateau of surviving levofloxacin-tolerant persisters. Subsequently, we obtained bacterial samples at five different time points during the formation and recovery of K. pneumoniae persisters to perform transcriptome analysis. ptsH gene was observed to be upregulated during the formation of persisters, and down-regulated during the recovery of the persisters. Further, we used CRISPR-Cas9 to construct ΔptsH, the ptsH-knockout K. pneumoniae strain, and to investigate the effect of ptsH on the persister formation. We observed that ptsH can promote the formation of persisters, reduce accumulation of reactive oxygen species, and enhance antioxidant capacity by reducing cyclic adenosine monophosphate (cAMP) levels. To the best of our knowledge, this is the first study to report that ptsH plays a vital role in forming K. pneumoniae persisters. This study provided important insights to further explore the mechanism underlying the formation of K. pneumoniae persisters and provided a potential target for treating infection with K. pneumoniae persisters.

Novel ideas for the comprehensive evaluation of varus knee osteoarthritis: radiological measurements of the morphology of the lateral knee joint.

BACKGROUND: The lateral anatomical and morphological characteristics of knees with varus knee osteoarthritis (OA) have not received sufficient attention. This study used several radiological parameters to describe the morphological characteristics of the lateral knee with OA to determine whether there are relationships between varus knee OA and parameters such as lateral plateau widening (LPW), proximal fibula curvature (PFC), and fibula height (FH). METHODS: The study retrospectively analyzed 1072 subjects who underwent standard radiography for diagnosing or evaluating symptomatic knee joint disease. The 163 Kellgren and Lawrence (K-L) grades 0 and I knees were categorized into the no-knee-OA group, and the 909 K-L grades II-IV knees were classified into the knee-OA group. Medial proximal tibial angle, joint line convergence angle, hip-knee-ankle angle, LPW, PFC, and FH were measured. T tests and chi-square tests were used to compare each index between the two groups. Binary logistic regression was performed to examine the correlation between indexes and knee OA occurrence. Ordinal logistic analysis, principal component analysis, and multivariable linear regression analysis were performed to examine the correlations between the three lateral parameters and K-L grades and the degree of varus deformity. RESULTS: LPW and PFC were significantly greater and FH was significantly smaller in the knee-OA group than in the no-knee-OA group. LPW, PFC, and FH were correlated with knee OA occurrence. One principal component, named the comprehensive principal component score of varus deformity, was extracted from the three indexes, and the total variance of the principal component interpretation was 76.60%. Ordinal logistics and multivariable linear regression analysis showed that, after adjusting for age and BMI, LPW and PFC were positively correlated with K-L grading and varus deformity. FH was significantly and negatively correlated with K-L grading and varus deformity (all P < 0.05). CONCLUSIONS: Regular morphological changes take place in the lateral knee with varus OA, including lateral dislocation of the tibial plateau, proximal fibula bending, and upward movement of the fibular head. Changes in LPW, PFC, and FH could enable a more comprehensive assessment of varus knee OA occurrence, severity, and deformity. Level of evidence Retrospective Study Level III.

Prognostic factors for medial open-wedge high tibial osteotomy with spacer implantation in patients with medial compartmental knee osteoarthritis.

BACKGROUND: To identify medial open-wedge high tibial osteotomy (MOWHTO) prognostic factors with wedge-shaped spacer implantation (spacer-type MOWHTO) for varus medial compartment knee osteoarthritis. METHODS: Patients who underwent spacer-type MOWHTO between August 2018 and September 2019 were prospectively enrolled in this study. Patients were divided into effective group and invalid group based on the Western Ontario and McMasters University Osteoarthritis Index (WOMAC) score one year postoperatively. The variables assessed at baseline and one year postoperatively including age, sex, body mass index (BMI), Kellgren-Lawrence (K-L) grade, hip-knee-ankle angle (HKAA), medial proximal tibial angle (MPTA), posterior tibial slope angle (PTSA), Blackburn-Peel index (BPI), duration of symptoms, and WOMAC score were compared. Prognostic factors were analyzed using logistic regression, and the corresponding odds ratios were also calculated. RESULTS: A total of 104 patients were enrolled in the study protocol at one year postoperatively. The WOMAC score decreased from 72.39 ± 12.95 at baseline to 20.06 ± 12.96 at one year postoperatively. Univariate analysis revealed that the significant predictors of the WOMAC score were age > 70 years, BMI > 30 kg/m2, K-L grade IV, and pre-HKAA > 10° (P < 0.1 for all). Multivariable logistic regression analysis revealed that age > 70 (OR = 4.861) and K-L grade IV (OR = 6.590) were significantly associated with the higher WOMAC score at one year postoperatively. CONCLUSIONS: Spacer-type MOWHTO is an effective treatment for osteoarthritis with varus deformity. The prognostic factors for spacer-type MOWHTO are age and K-L grade.

Use of a suspended and straightened knee joint position when fixing steel plates can prevent the increase in postoperative posterior tibial slope after open­wedge high tibial osteotomy.

BACKGROUND: Posterior tibial slope (PTS) increases after medial open-wedge high tibial osteotomy (OWHTO) is challenging for patients. This study aims to determine whether use of a suspended and straightened knee joint position during the fixing of steel plates can prevent an increase in the PTS after OWHTO. METHODS: This study retrospectively analyzed 112 subjects (122 knees) [34 males, 78 females; mean age 59.1 ± 6.6 (range 48-76) years; mean body mass index 28.06 ± 3.61 kg/m2] who underwent OWHTO. A total of 78 knees that were suspended and extended by placing a sterile cloth ball under the ipsilateral ankle during the fixing of steel plates comprised the suspended and straightened knee joint position (SSP) group, and 44 knees that were kept naturally straightened without placing a sterile cloth ball under the ipsilateral ankle during the fixing of steel plates comprised the naturally straightened knee joint position (NSP) group. Patients were clinically assessed according to the visual analog pain scale (VAS), the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index, the Knee Society Scores (KSS) knee and function scores, the Hospital for Special Surgery (HSS) knee scores and the Lysholm knee scores. Radiological assessment was performed according to the changes in the PTS between preoperation, 1-day postoperation, and the final follow-up periods. Ultimately, the difference in postoperative PTS changes between the two groups was statistically analyzed. The median follow-up period was 2.2 years (range 1.6-3.7 years). RESULTS: In the final follow-up period, significant improvements were observed in the clinical VAS scores, WOMAC scores, KSS knee and function scores, HSS scores and the Lysholm knee scores in both groups (P < 0.001), and no difference was found between the two groups. Radiological assessment showed that there was no statistical difference in the preoperative PTS between the two groups. The 1-day postoperative PTS and the most recent follow-up PTS were significantly greater than the preoperative PTS in the NSP group (t = - 3.213, - 6.406, all P < 0.001), but no significant increase was seen in the SSP group (P > 0.05). The increase in PTS in the NSP group was significantly greater than that in the SSP group at the 1-day postoperative (t = 2.243, P = 0.030) and final follow-up periods (t = 6.501, P < 0.001). CONCLUSIONS: For OWHTO, the use of a suspended and straightened knee joint position rather than a naturally straightened knee joint position during the fixing of steel plates could effectively prevent the increase in postoperative PTS. LEVEL OF EVIDENCE: Retrospective Study Level III.

[Analysis of the effect of asymptomatic hyperuricemia on the effectiveness after arthroscopic rotator cuff repair].

OBJECTIVE: To investigate the effect of asymptomatic hyperuricemia on the effectiveness of arthroscopic rotator cuff repair. METHODS: The clinical data of 80 patients who underwent arthroscopic rotator cuff repair and met the selection criteria between March 2018 and December 2019 were retrospectively analyzed. According to the serum uric acid level, the patients were divided into hyperuric acid group (46 cases, the serum uric acid level was more than 417 µmol/L in males and was more than 357 µmol/L in females) and normal group (34 cases, serum uric acid level was lower than the above standard). There was no significant difference in gender, age, side, body mass index, blood glucose level, total cholesterol level, rotator cuff tear size, and preoperative shoulder motion, visual analogue scale (VAS) score, University of California-Los Angeles (UCLA) score, Constant score, American Shoulder and Elbow Surgeons (ASES) score, and other general data between the two groups ( P>0.05). The range of motion of abduction, forward flexion, and external rotation at 90° abduction were recorded and compared between the two groups before operation and at last follow-up; the improvement of shoulder pain was evaluated by VAS score; the improvement of shoulder function was evaluated by UCLA score, Constant score, and ASES score; and the shoulder joint MRI grade was evaluated according to Sugaya evaluation criteria. RESULTS: All patients were followed up 9-16 months, with an average of 11.9 months; there was no significant difference in the follow-up time between the two groups ( t=0.968, P=0.336). There were 2 cases of retear in the hyperuric acid group (including 1 case of severe tear) and 1 case of light retear in the normal group. The remaining patients in the two groups had no early-related complications. At last follow-up, the range of motion of the shoulder joints (abduction, forward flexion, external rotation at 90° abduction), VAS score, UCLA score, Constant score, and ASES score of the two groups were significantly improved when compared with preoperative ones ( P<0.05); the above indicators in the normal group were significantly better than those in the hyperuric acid group ( P<0.05). The MRI grade of the shoulder joint in the normal group was significantly better than that in the hyperuric acid group ( Z=-2.000, P=0.045). CONCLUSION: Compared with patients with normal serum uric acid level, asymptomatic hyperuricemia can lead to worse recovery after arthroscopic rotator cuff repair in patients with rotator cuff tears.

Normal parathyroid hormone and non-proliferative diabetic retinopathy in patients with type 2 diabetes.

AIMS/INTRODUCTION: To investigate the associations between parathyroid hormone (PTH) and non-proliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Data were collected from 2,322 patients with type 2 diabetes mellitus in hospital between 2017 and 2019. The odds ratio (OR) and the corresponding 95% confidence interval related to the quartiles of PTH were obtained by logistic regression analysis after adjusting the potential confounding variation. RESULTS: The patients were stratified into quartiles (Q1-Q4) based on the PTH levels, with the cut-off limits of ≤23.74, 23.74-29.47, 29.47-37.30 and >37.30 pg/mL in men, and ≤24.47, 24.47-31.22, 31.22-39.49 and >39.49 pg/mL in women. The first quartile (Q1) represents the lowest quartile and the fourth quartile (Q4) is the highest. According to the quartiles (Q1-Q4), the prevalence rate of NPDR in patients showed a significantly decreasing trend (37.9%, 36.3%, 34.0% vs 24.0% in men; 43.2%, 40.5%, 31.1% vs 26.2% in women, both P < 0.05). Independent of age, diabetes duration and other metabolic factors, multivariate logistic regression showed that participants in Q4 had a lower OR of NPDR than those in Q1 (OR 0.443, 95% confidence interval 0.300-0.654, P < 0.001 for men; OR 0.428, 95% confidence interval 0.283-0.646, P < 0.001 for women). CONCLUSIONS: Low serum PTH levels were significantly associated with complications of NPDR in inpatients. Its causality remains to be further studied.

Serum progesterone and retinopathy in male patients with type 2 diabetes: A cross-sectional study.

AIMS/INTRODUCTION: The aim of this study was to investigate the relationship between serum progesterone (P) and retinopathy in male patients with type 2 diabetes mellitus, and to investigate whether P is associated with its progression. MATERIALS AND METHODS: A total of 1,376 male participants with type 2 diabetes mellitus were recruited from Affiliated Hospital of Medical College Qingdao University (Qingdao, China). Through logistic regression analysis after adjusting the potential confounding variation, the odds ratio (OR) and the corresponding 95% confidence interval related to the quartiles of progesterone were obtained. RESULTS: According to the quartiles of P levels, the prevalence rate of diabetic retinopathy (DR) in the last quartile is obviously greater to other quartiles (52.5-34.9%, 31.9%, 37.5%, P < 0.001). Compared with those in the first quartile, the prevalence of DR for the last quartile had an OR of 1.85 in the non-proliferative diabetic retinopathy group, while the OR was 8.35 in the proliferative diabetic retinopathy group (P < 0.001, unadjusted model). When adjusted for age, body mass index, duration of type 2 diabetes mellitus, glycated hemoglobin, blood pressure and other variables, the ORs for DR in the fourth quartile were 2.13 (95% confidence interval 1.49-3.06) in the non-proliferative diabetic retinopathy group and 8.44 (95% confidence interval 2.69-26.43) in the proliferative diabetic retinopathy group (P < 0.001). The positive association between P and DR risk was independent in adjusted logistic regression. CONCLUSIONS: High levels of serum progesterone are significantly associated with DR in male hospitalized patients. This could mean that a higher P level in men is a potential clinical factor to identify DR, and the causality remains to be further explored.