Objective: To investigate the role of butyric acid-producing bacteria in long bone homeostasis in mice with periodontitis under a high-fat/high-sugar diet and to provide new insights for the prevention and treatment of periodontitis and related bone metabolic diseases. Methods: This study has been approved by the Animal Welfare and Ethics Committee of the Experimental Animal Center. Initially, 14 mice were randomly divided into the CON group (the control group) and the LIG group (the periodontitis group). Mice in the LIG group had experimental periodontitis induced by ligating the second maxillary molars bilaterally and were fed a high-fat and high-sugar diet. After 8 weeks, samples were collected. Micro-computed tomography (Micro-CT) was used to analyze alveolar bone resorption and various parameters of the proximal tibia trabecular bone, including bone mineral density (BMD), bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). After decalcification, hematoxylin and eosin (HE) staining was performed on maxillary bone sections to assess periodontal tissue inflammation and connective tissue destruction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect related genes in the distal femur and proximal tibia bone tissues, including osteocalcin (OCN), osteogenic transcription factor (Osterix), osteoprotegerin (OPG), tartrate resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), receptor activator of nuclear factor kappa-B (RANK), and receptor activator of nuclear factor kappa-B ligand (RANK-L). Subsequently, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + butyric acid-producing bacteria (BP) group, and LIG + BP group. The breeding, sampling, and sample detection methods remained the same. Finally, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + sodium butyrate (SB) group, and LIG + SB group. The breeding, sampling, and sample detection methods remained the same. Results: ①Periodontitis modeling was successful. Compared with the CON group, the LIG group exhibited significant alveolar bone resorption of the maxillary second molar, aggravated periodontal tissue inflammation, and connective tissue destruction. ②Periodontitis exacerbated long bone resorption in mice fed a high-fat high-sugar diet. Compared with the CON group, the LIG group had significantly lower BMD, BV/TV, Tb.N, and Tb.Th (P<0.05), and significantly higher Tb.Sp (P<0.05). HE staining of the proximal tibia showed that the trabeculae in the LIG group were sparse and disordered, with some areas showing fractures or dissolution. The expression of osteoblast markers (OCN, Osterix, OPG) was significantly lower in the LIG group (P<0.05), while the expression of the osteoclast marker TRAP showed an increasing trend (P>0.05). The ratio of RANK-L/OPG was significantly higher in the LIG group compared with the CON group (P<0.05). ③ Supplementation with butyric acid-producing bacteria alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BMD and Tb.Th were significantly higher in the LIG + BP group. HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + BP group compared with the LIG group. The expression of OCN and Osterix was significantly higher in the LIG + BP group, while the expression of osteoclast-specific genes (OSCAR, RANK, RANK-L) was significantly lower (P<0.05). ④ Supplementation with butyrate alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BV/TV and Tb.N were significantly higher in the LIG + SB group, and Tb.Sp was significantly lower (P<0.05). HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + SB group compared with the LIG group. The expression of Osterix, OPG, OSCAR, TRAP, and RANK was significantly lower in the LIG + SB group compared with the LIG group (P<0.05). Conclusion Periodontitis disrupts the long bone homeostasis of mice fed a high-fat high-sugar diet, aggravating long bone resorption. Supplementation with butyric acid-producing bacteria or butyrate can effectively alleviate the disruption of long bone homeostasis caused by periodontitis.

BACKGROUND:For elderly patients with traumatic hip fractures,the related factors of prognosis are very complex,and the integrity of the lateral wall is one of the influencing factors.It is of important clinical value to understand the effect of lateral wall injury on the prognosis of femoral intertrochanteric fracture. OBJECTIVE:To evaluate the relationship between the integrity of the lateral wall and hip functional recovery and other outcomes in patients with femoral intertrochanteric fractures. METHODS:Totally 82 patients with femoral intertrochanteric fractures were screened and all patients received proximal femoral nail antirotation fixation.According to the thickness of the lateral wall,the patients were divided into the lateral wall intact group(n=31)and lateral wall risk group(n=51).The perioperative indexes,weight-bearing time,fracture healing time,hip joint function and range of motion,postoperative pain and complications were compared between the two groups. RESULTS AND CONCLUSION:(1)The time of hospitalization and the number of fluoroscopies during operation in the lateral wall intact group were significantly lower than those in the lateral wall risk group(P<0.05),but there was no significant difference in other perioperative indexes.(2)Both groups were able to get down to the ground early after surgery and finally complete weight-bearing,but in the lateral wall risk group,the time of fracture healing was longer;the time of complete weight-bearing was significantly delayed;the Harris score of the last follow-up was lower;the range of motion of hip extension and flexion and neck trunk angle on the affected side were smaller(P<0.05).(3)There was no significant difference in the incidence of postoperative complications between the two groups,but the overall incidence of complications in the lateral wall intact group was significantly lower(P<0.05).(4)In summary,after internal fixation of proximal femoral nail antirotation,patients with the intact lateral wall had a relatively better prognosis than those with risk lateral wall.

【Objective】 To investigate the urinary tract characteristics of diabetes insipidus (DI) complicated with upper urinary tract dilatation (UUTD), and to summarize the treatment experience. 【Methods】 The clinical data of 28 DI patients treated in China Rehabilitation Research Center were retrospectively analyzed with UUTD and all urinary tract dysfunction (AUTD) systems to evaluate the urinary tract characteristics. The relevant laboratory results, video-urodynamic recordings (VUDS), UUTD, neurophysiologic tests, treatment regimens and follow-up data were summarized. 【Results】 There were 21 DI cases (75.0%) and 7 cases of DI with neurogenic bladder (NB). Polyuria, polydipsia, urine specific gravity, urine osmotic pressure and water deprivation vasopressin test had diagnostic value for DI. In addition, detailed history, neurological examination, VUDS and neurophysiologic tests had significant diagnostic value for DI with NB. Enterocystoplasty was recommended for 2 DI with NB patients with poor bladder capacity, compliance and renal impairment. For the remaining 26 patients, individualized medication combined with bladder neck incision and appropriate bladder management, including intermittent catheterization, catheter indwelling and regular voiding, achieved satisfactory results. High serum creatinine decreased from (269.8±105.7)μmol/L to (164.4±90.2)μmol/L in 13 patients with abnormal renal function. Forty-eight dilated ureters showed significant improvement in the UUTD grade, and the median grade decreased from 3 to 2. 【Conclusion】 Bladder distension, trabeculation and decreased or absent sensations were common features for DI patients with UUTD. Individualized therapy by medication combined with appropriate bladder management can improve the dilatation and renal function.

Purpose: We investigated the effectiveness of intravesical botulinum toxin-A (BTX-A) injection therapy in patients with lower urinary tract dysfunction (LUTD) and upper urinary tract (UUT) deterioration and evaluated whether BTX-A injection therapy could substitute for augmentation uretero-enterocystoplasty (AUEC). Methods: Data from a prospective, single-center cohort from 2017–2021 were analyzed. Patients were divided into 2 treatment groups: AUEC and BTX-A (i.e., patients who declined AUEC). Bladder and UUT functions were assessed by comparing clinical information, urodynamic data, laboratory results, and imaging records. Results: In total, 121 patients were enrolled (BTX-A group: 41 patients; AUEC group: 80 patients). The BTX-A group showed a reduced maximum detrusor pressure and increases in the maximum bladder volume and bladder compliance (P<0.05). However, in follow-up evaluations, significantly smaller improvements (all P<0.05) in urodynamic parameters were found in the BTX-A group than in the AUEC group. Notably, there was no significant improvement in vesicoureteral reflux (VUR; P=0.66) or upper urinary tract dilatation (UUTD; P=0.75) in the BTX-A group, and no statistically significant difference in serum creatinine (Scr) levels or the estimated glomerular filtration rate (eGFR) was observed in the follow-up evaluations (all P>0.05). Both VUR and UUTD improved significantly in the AUEC group, and the Scr and eGFR levels significantly improved after AUEC relative to baseline levels (P<0.05). The reduction in the Scr level was significantly lower in the BTX-A group than in the AUEC group during 0–15 months of follow-up (Scr reduction differences, -1.36; P<0.01). Conclusions Although BTX-A injection therapy was effective for improving bladder function, BTX-A injections did not alleviate UUT deterioration in this study, particularly in patients with advanced-stage LUTD. Conversely, AUEC for LUTD has a well-established role in improving UUT function. Hence, BTX-A injection therapy should not replace AUEC to ameliorate UUT impairment and protect UUT function.

Objective:To investigate the long-term efficacy and complications of augmentation uretero-enterocystoplasty (AUEC).Methods:The clinical data of 262 patients with lower urinary tract dysfunction who underwent AUEC at our center from January 2003 to June 2022 were analyzed retrospectively. There were 193 males and 69 females, the median age was 24 (4, 67) years, the median disease duration was 12.0 (0.2, 56.0) years and the preoperative creatinine was 91.5 (68.1, 140.0) μmol/L. 320 ureters had high-grade UUTD, 216 ureters had VUR, 14 of which had low-pressure reflux.The number of low-grade VUR ureter was 22 (10.2%) and the number of high-grade VUR ureter was 194 (89.8%). Video-urodynamics showed that the maximum bladder capacity was 102 (47, 209) ml, the maximum detrusor pressure was 33.0 (15.5, 50.5) cmH 2O, and the bladder compliance was 6.4 (3.0, 12.3) ml/cmH 2O. All patients underwent AUEC. The surgical method is to cut a segment of sigmoid colon, open the sigmoid colon along the mesenteric margin, fold and suture it into " U" or " S" shaped intestinal mesh according to the principle of " detubulization" . At the same time, perform ureteroplasty and replanting, and then anastomosis the intestinal mesh with the opened bladder flap to form an expanded new bladder. Follow-up was performed via outpatient clinic or telephone. The creatinine, maximum bladder capacity, maximum detrusor pressure, bladder compliance, ureteral reflux and upper urinary tract dilatation were compared preoperatively and postoperatively. The postoperative complications were also evaluated. Results:The median follow-up time was 57.4 (4, 151) months after surgery. At 1-3 months after surgery, the maximum bladder capacity and bladder compliance increased to 303.9% and 189.9% of the preoperative level, and the maximum detrusor pressure decreased to 63.6% of the preoperative level. At 6-10 years after surgery, the maximum bladder capacity and bladder compliance increased to 490.2% and 627.9% and the maximum detrusor pressure decreased to 25.8% of the preoperative level. The UUTD of the patients was significantly reduced after surgery. The number of the high grade UUTD decreased to 116 (116/398, 29.2%) at 1-3 months and 51 (51/274, 18.6%) at 4-6 months. At 6-10 years, the number of the high-grade UUTD decreased to 4 (4/76, 5.3%) ( P<0.001), which was significantly lower than that before operation. The VUR was significantly relieved after operation, and 393 ureters had no VUR at 1-3 months, accounting for 97.8% (393/402) of the total ureters. Sustained remission of VUR was observed during follow-up. 73 ureters had no VUR at 6-10 years, accounting for 96.1% (73/76) of total ureters ( P<0.001). Patients' creatinine decreased to 79.0 (65.0-128.2) μmol/L at 1-3 months postoperatively, with a downward trend but no statistical difference, and creatinine levels were not significantly elevated at any postoperative time point compared with preoperative levels ( P>0.05). Postoperative complications included metabolic acidosis in 26 cases (9.9%), vesicoureteral anastomosis stenosis in 15 cases (5.7%), recurrent urinary tract infection in 16 cases (6.1%), and urinary calculi in 20 cases (7.6%), and intestinal obstruction requiring laparotomy in 8 cases (3.1%), all of them could be improved after treatments. Conclusions:AUEC is a safe and effective method for treating high-grade VUR or VUR with impaired anti-reflux mechanism, high-grade UUTD or UUTD with ureteral or vesicoureteral junction obstruction, and all of the complications can be improved after treatment. This technique can increase the bladder capacity and compliance, reconstruct the anti-reflux mechanism, and release upper urinary tract obstruction. It may play an important role in stabilizing and protecting the residual renal function from further deterioration.

Purpose: To explore the effect of intravesical electrical stimulation (IVES) on urinary adenosine triphosphate (ATP) and nitric oxide (NO) in rats with detrusor underactivity (DU) induced by bilateral pelvic nerve crush (bPNC), and to determine the underlying peripheral mechanism. Methods: Twenty-four female Sprague-Dawley rats were equally divided into 3 groups: sham; bPNC; and IVES. Rats in the IVES group began to receive IVES treatment 10 days after bPNC (20 minutes per day for 14 consecutive days). After the 14th IVES, rat urine was collected and cystometry was performed. The serum creatinine, blood urea nitrogen, and urinary ATP and NO levels were measured, and a routine urinalysis was performed. Results: The maximum cystometric capacity (MCC), maximum changes in bladder pressure during filling (∆FP), and postvoid residual urine (PVR) in the IVES group were significantly lower than the bPNC group, and the maximum changes in bladder pressure during voiding (∆VP) was significantly higher than the bPNC group. Compared with the sham group, the MCC, ∆FP and PVR were significantly increased, and the maximum voiding pressure (MVP) and ∆VP were significantly decreased in the bPNC group. After bPNC, urinary ATP was significantly decreased, and urinary NO was significantly increased. In IVES-treated rats, urinary ATP was significantly higher than the bPNC group, and NO was significantly lower than the bPNC group. In addition, the ATP-to-NO ratio of the rats in the bPNC group was significantly lower than the sham and IVES groups. Correlation analysis showed that the ATP and NO were not correlated with the MCC, ∆FP, MVP, ∆VP, and PVR. Conclusions Promoting the release of urothelial ATP and inhibiting the release of urothelial NO may be one of the peripheral mechanisms underlying IVES in the treatment of DU. Specifically, IVES may shift the balance between excitation and inhibition toward excitation.

Objective:Evaluate the influence of different pressure transmission media of urodynamic water filled catheter(WFC) and air charged catheter(ACC) on the pressure measurement results to determine whether they can be used interchangeably.Methods:The results of 2 147 patients who underwent urodynamic examination in our hospital from January 2014 to December 2020 were retrospectively analyzed. A total of 2 538 times of bladder manometry data were obtained, including 1 299 times in WFC group, 856 times in male and 443 times in female, aged 37(24, 50)years, course of disease 1.2(0.4, 5.0) years, 1 130 times in neurogenic bladder(NB)and 169 times in non-neurogenic bladder(N-NB); In ACC group, there were 1 239 times, 773 times for male and 466 times for female, with age of 37(24, 55)years, course of disease of 1.5(0.5, 6.0)years, 1 040 times for Nb and 199 times for N-NB. There was no significant difference in baseline data of general clinical data between the two groups. The intravesical pressure(Pves), intra-abdominal pressure(Pabd)and detrusor pressure(Pdet) of WFC and ACC patients during filling and urination were analyzed. For traumatic spinal cord injury(SCI) and idiopathic patients, the two sets of pressure measurement data were analyzed separately. Nonparametric test and Chi-square test were used to compare the Pves, Pabd, and Pdet recorded by the two manometry catheters before, at the end and after urination, the maximum detrusor pressure at DO(Pdet.max-DO), and the maximum detrusor pressure during spontaneous urination (Pdet. max) and the detrusor pressure (Pdet.Qmax) corresponding to the maximum urine flow rate, the maximum urethral pressure (MUP) and the maximum urethral closure pressure (MUCP) during resting urethral pressure profile, and the initial cough Pdet signal pattern (typeⅠ, typeⅡand typeⅢ).Results:Regardless of the cause, the Pabd values measured by ACC were significantly higher than WFC before filling, end filling and after voiding[18(10, 26)cmH 2O vs.15(11, 21)cmH 2O; 23(16, 31)cmH 2O vs. 20(14, 26)cmH 2O; 23(15, 31)cmH 2O vs.18(12, 24)cmH 2O], and Pdet were significantly lower than WFC[0(0, 0) cmH 2O vs. 0(0, 1)cmH 2O; 5(1, 13)cmH 2O vs. 9(4, 17)cmH 2O; 6(1, 12)cmH 2O vs. 7(3, 14)cmH 2O]. In the initial cough state, Pves and Pabd increase value were also significantly lower than that of WFC [22(12, 36)cmH 2O vs. 23(14, 38)cmH 2O; 20(10, 33)cmH 2O vs. 21(12, 36)cmH 2O]. The Pves measured by ACC was also significantly higher than WFC before filling and after voiding[18(10, 27)cmH 2O vs. 16(11, 21)cmH 2O; 30(22, 39)cmH 2O vs. 26(20, 36)cmH 2O]. Maximum urethral pressure (MUP) and maximum urethral closure pressure (MUCP) measured by ACC were significantly higher than WFC [91(69, 118)cmH 2O vs.81(64, 106)cmH 2O; 77(55, 103)cmH 2O vs. 68(48, 91)cmH 2O], and there were no significant differences in Pdet.max-DO、Pdet.max和Pdet.Qmax. For patients with traumatic SCI, the Pves measured by ACC was significantly higher than WFC before filling[15(10, 24)cmH 2O vs. 14(10, 20)cmH 2O], and only MUP was significantly higher than WFC in the measurement of urethral pressure[95(71, 119)cmH 2O vs. 85(65, 112)cmH 2O], and there were no significant differences in Pdet.max-DO, Pdet.max, Pdet.Qmax and MUCP. For idiopathic patients, Pves measured by ACC before filling and after urination were significantly higher than WFC[25(20, 29)cmH 2O vs. 18(11, 23)cmH 2O; 35(29, 44)cmH 2O vs. 28(20, 38)cmH 2O], while Pdet.max-DO, Pdet.max, Pdet.Q max, MUP and MUCP were not significantly different in different pressure measurement systems. For the comparison of the initial cough Pdet signal pattern, ACC is easier to detect type Ⅰ, and WFC is easier to detect type Ⅱ and type Ⅲ. Conclusions:Compared with WFC, ACC measured higher Pves and Pabd and lower Pdet in resting state, and lower Pves and Pabd in initial cough state. The pressure values and signal pattern measured by WFC and ACC are not completely consistent, so they cannot be used interchangeably.

Background: Intestinal flora disorder plays an important role in the pathogenesis of chronic constipation. Either microbial agents or fecal microbiota transplantation has therapeutic effect on chronic constipation by regulating the intestinal flora. Aims: To study the characteristics of intestinal flora structure in elderly chronic constipation patients. Methods: Thirty elderly patients with chronic constipation from January 2019 to December 2019 at Nanjing Central Hospital were enrolled, and 30 elderly healthy subjects were served as controls. Stool was collected, and 16S rRNA high-throughput sequencing method was used to analyze the structure of intestinal flora. Results: Alpha diversity analysis showed that there were no significant differences in Ace, Chao, Shannon and Simpson indices between chronic constipation group and healthy control group. Twenty dominant genera accounting for more than 80% of all genera were identified in the two groups, Bacteroides was the most abundant genus. Beta diversity analysis showed that the species composition between the two groups was different, the characteristics of the two groups were not similar (R=0.098, P=0.001). Relative abundances of Prevotella, Faecalibacterium and Lachnospira were higher in the healthy control group, while Ruminococcus, Shigella, Parabacteroides and Alistipes were higher in chronic constipation group. Numbers of species with significantly different relative abundance in healthy control group and chronic constipation group were 25 and 2, respectively. Compared with healthy control group, the abundance of Alistipes, Oscillospira, Ruminococcus and Parabacteroides were higher in chronic constipation group (P< 0.05), while Megasphaera was lower (P< 0.05). Conclusions: There is no difference in the diversity of intestinal flora between elderly chronic constipation patients and elderly healthy controls, however, significant difference is detected in species composition. Therefore, targeting at modifying intestinal flora may be a promising therapeutic strategy for chronic constipation.

BACKGROUND: In the process of bone defect healing, the use of biological materials loaded with drugs for local defect intervention can accelerate the repair of the defect, which provides a new method for the local treatment of bone defects. OBJECTIVE: To introduce the local application of bone tissue engineering scaffolds loaded with bisphosphonates in bone defect repair and to summarize the effects of bone tissue engineering scaffolds as a drug delivery system on the bone defect healing. METHODS: The authors retrieved PubMed, Web of Science, Springerlink, Medline, WanFang and CNKI databases with "bisphosphonates, alendronate, zoledronate, bone defect, bone tissue engineering" as key words for relevant articles published from 2006 to 2018. Initially, 235 articles were retrieved, and finally 70 articles were selected for further analysis. RESULTS AND CONCLUSION: Bisphosphonate drug is an effective inhibitor of osteoclast dissolution. It can form a drug sustained release system on the local defect by being loaded to composite scaffolds, promote the formation of new bone and accelerate the healing of the defect. For the drug delivery system of bisphosphonates, suitable scaffold materials are crucial to the osteogenic effect of composite scaffolds in the defect area. At present, the carrier materials used for bisphosphonate-loaded composite scaffolds are mainly divided into organic materials and inorganic materials. Most polymeric organic materials can directly load bisphosphonates to form good drug sustained release in the local area and obviously exert their pro-osteogenic effects, while natural materials and most inorganic materials are often combined with other materials to form composite materials as carriers to optimize the carrier performance. Most studies have also confirmed that these composite materials loaded with bisphosphonates in the defect area exert osteogenic effect in the defect area.

BACKGROUND:With the development of three-dimensional (3D) printing technology, 3D printed porous titanium scaffolds as bone substitutes have become a research hotspot. OBJECTIVE:To introduce and discuss the effects of each parameter of 3D printed porous titanium scaffolds on bone ingrowth, and to sum out the optimal parameters for bone ingrowth. METHODS:The first author retrieved PubMed, Springerlink and Medline databases with“three-dimensional (3D) printing, scaffold, titanium, bone ingrowth”as keywords for relevant articles published from 2006 to 2016. 125 articles were retrieved initial y, and final y 42 eligible articles were included for analysis. RESULTS AND CONCLUSION:Pore size, porosity, pore structures and surface modifications of 3D printed porous titanium scaffolds al make effects on bone ingrowth or osteoblasts in scaffolds. Scaffolds with appropriate pore size and porosity can promote the vascularization and provide adequate nutrition and oxygen supplement, to ensure high cel viability. Regulations of cel performances, such as cel attachment, proliferation and differentiation, are also affected by pore structures and nano-scale surface modification. Herein, a detailed combination of the parameters, as mentioned above, can create a better porous scaffold for better bone ingrowth. Hence, the high-stability interface between bone and scaffolds may be obtained through the parameter adjustment.