Special type of distal junctional failure exhibits pelvic incidence changes: sacroiliac joint-related pain following lumbar spine surgery.

Background: Currently, change in pelvic incidence (PI) in patients after spinal surgery have not been associated with clear clinical symptoms. This study sought to compare changes in the sagittal parameters of different patients before and after thoracolumbar spine surgery, the relationship between PI change and sacroiliac joint pain (SIJP) after surgery was clarified, and the correlation between PI change and sacroiliac joint (SIJ) activity was verified. Methods: This study retrospectively analyzed the data of patients who underwent thoracolumbar fusion at Sun Yat-sen Memorial Hospital from January 2019 to June 2021. The spinal and pelvic parameters [including pelvic tilt (PT), sacral slope (SS), PI, lumbar lordosis (LL) angle, etc.] of 409 patients with standard standing lateral radiographs before and after surgery were compared and analyzed. Postoperative follow-up of all patients with standardized SIJP assessment. The incidence of postoperative SIJP, and its correlation with sagittal parameters of the spine and pelvis, surgical methods, and the basic characteristics of patients were analyzed. The Chi-square test was used for categorical variables, the independent-sample t-test was used for generally conformed normally distributed continuous variables. Risk factors associated with the development of SIJP were analyzed using logistics regression. Correlations among SS, PI, and the 4 other sagittal parameters were analyzed using the Pearson correlation coefficient (r). Results: Postoperative PI changes tended to be larger in the lowest instrumented vertebra (LIV) (L4 and above: 1.63°; L5: 2.43°; S1: 3.83°; P<0.05) and longer fixed segment. The risk factors for SIJP included a PI >4° [odds ratio (OR) =13.051; P<0.001], LIV S1 (OR =3.378; P=0.023), and fixed total segment ≥3 (OR =2.632; P=0.038). ∆PI was significantly correlated with ∆SS in patients with non-S1 distal fixation vertebrae (R2=0.388; P<0.01), but no such correlation was found in patients with S1 distal fixation vertebrate. Conclusions: Changes in PI values after thoracolumbar spine surgery can correctly reflect the motion state of the SIJ. Excessive changes in PI (>4°) are similar to the mechanism of distal junctional kyphosis (DJK), while such changes make patients prone to SIJP following lumbar spine surgery.

Examining patterns of traditional Chinese medicine use in pediatric oncology: A systematic review, meta-analysis and data-mining study / 中西医结合学报

BACKGROUND@#Traditional Chinese medicine (TCM) is becoming a popular complementary approach in pediatric oncology. However, few or no meta-analyses have focused on clinical studies of the use of TCM in pediatric oncology.@*OBJECTIVE@#We explored the patterns of TCM use and its efficacy in children with cancer, using a systematic review, meta-analysis and data mining study.@*SEARCH STRATEGY@#We conducted a search of five English (Allied and Complementary Medicine Database, Embase, PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov) and four Chinese databases (Wanfang Data, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and VIP Chinese Science and Technology Periodicals Database) for clinical studies published before October 2021, using keywords related to "pediatric," "cancer," and "TCM."@*INCLUSION CRITERIA@#We included studies which were randomized controlled trials (RCTs) or observational clinical studies, focused on patients aged < 19 years old who had been diagnosed with cancer, and included at least one group of subjects receiving TCM treatment.@*DATA EXTRACTION AND ANALYSIS@#The methodological quality of RCTs and observational studies was assessed using the six-item Jadad scale and the Effective Public Healthcare Panacea Project Quality Assessment Tool, respectively. Meta-analysis was used to evaluate the efficacy of combining TCM with chemotherapy. Study outcomes included the treatment response rate and occurrence of cancer-related symptoms. Association rule mining (ARM) was used to investigate the associations among medicinal herbs and patient symptoms.@*RESULTS@#The 54 studies included in this analysis were comprised of RCTs (63.0%) and observational studies (37.0%). Most RCTs focused on hematological malignancies (41.2%). The study outcomes included chemotherapy-induced toxicities (76.5%), infection rate (35.3%), and response, survival or relapse rate (23.5%). The methodological quality of most of the RCTs (82.4%) and observational studies (80.0%) was rated as "moderate." In studies of leukemia patients, adding TCM to conventional treatment significantly improved the clinical response rate (odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.49-4.36), lowered infection rate (OR = 0.23; 95% CI = 0.13-0.40), and reduced nausea and vomiting (OR = 0.13; 95% CI = 0.08-0.23). ARM showed that Radix Astragali, the most commonly used medicinal herb (58.0%), was associated with treating myelosuppression, gastrointestinal complications, and infection.@*CONCLUSION@#There is growing evidence that TCM is an effective adjuvant therapy for children with cancer. We proposed a checklist to improve the quality of TCM trials in pediatric oncology. Future work will examine the use of ARM techniques on real-world data to evaluate the efficacy of medicinal herbs and drug-herb interactions in children receiving TCM as a part of integrated cancer therapy.

Synthesis of chiral pyrimidine-substituted diester D-A cyclopropanes via asymmetric cyclopropanation of phenyliodonium ylides.

A highly enantioselective cyclopropanation to synthesize pyrimidine-substituted diester D-A cyclopropanes is reported. Various N1-vinylpyrimidines react well with phenyliodonium ylides, delivering chiral cyclopropanes in up to 97% yield with up to 99% ee. Through simple [3+2] annulation with benzaldehyde or ethyl glyoxylate, different chiral pyrimidine nucleoside analogues with a sugar ring could be obtained.

Abnormal hypermethylation and clinicopathological significance of FBLN1 gene in cutaneous melanoma.

Fibulin-1 (FBLN1) is involved in the progression of some types of cancer. However, the role of FBLN1 in cutaneous melanoma (CM) has not been examined. The purpose of this study was to understand the molecular mechanisms and clinical significance of FBLN1 inactivation in CM. The expression of FBLN1 mRNA in CM tissues and adjacent normal skin tissues was analyzed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Methylation-specific polymerase chain reaction was performed to examine the methylation status of the FBLN1 gene promoter. Furthermore, the methylation status of FBLN1 was analyzed with the clinicopathological characteristics and overall survival. qRT-PCR showed FBLN1 mRNA levels in cancerous tissues to be significantly decreased compared with that in adjacent normal skin tissues. The rate of FBLN1 promoter methylation was significantly higher in CM tissues than in adjacent normal skin tissues (P < 0.001). Downregulation of FBLN1 was strongly correlated with promoter methylation (P = 0.021). Promoter hypermethylation of FBLN1 was significantly associated with tumor stage (P = 0.019). In addition, FBLN1 methylation status was associated with significantly shorter survival time and was an independent predictor of overall survival. In conclusion, our results indicated that FBLN1 is a novel candidate of tumor suppressor gene and that promoter hypermethylation of FBLN1 is associated with tumor progression in CM.

Molecular dynamics simulations of void defects in the energetic material HMX.

A molecular dynamics (MD) simulation was carried out to characterize the dynamic evolution of void defects in crystalline octahydro-1, 3, 5, 7-tetranitro-1, 3, 5, 7-tetrazocine (HMX). Different models were constructed with the same concentration of vacancies (10 %) to discuss the size effects of void. Energetic ground state properties were determined by annealing simulations. The void formation energy per molecule removed was found to be 55-63 kcal/mol(-1), and the average binding energy per molecule was between 32 and 34 kcal/mol(-1) according to the change in void size. Voids with larger size had lower formation energy. Local binding energies for molecules directly on the void surface decreased greatly compared to those in defect-free lattice, and then gradually increased until the distance away from the void surface was around 10 Å. Analysis of 1 ns MD simulations revealed that the larger the void size, the easier is void collapse. Mean square displacements (MSDs) showed that HMX molecules that had collapsed into void present liquid structure characteristics. Four unique low-energy conformers were found for HMX molecules in void: two whose conformational geometries corresponded closely to those found in HMX polymorphs and two, additional, lower energy conformers that were not seen in the crystalline phases. The ratio of different conformers changed with the simulated temperature, in that the ratio of α conformer increased with the increase in temperature.

Serum soluble MICB (sMICB) correlates with disease progression and survival in melanoma patients.

Recently, it was reported that soluble MICB (sMICB) may impair tumor immunogenicity by reducing natural killer group 2D ligand densities on malignant cells. The aim of this study was to elucidate the role of sMICB in melanoma patients. In the present study, we determined sMICB serum concentration in 125 melanoma patients of different clinical stages of disease compared with 30 healthy controls using an ELISA. The correlations between sMICB serum concentration and clinicopathologic variables were analyzed. sMICB serum level was significantly elevated (P < 0.0005) in melanoma patients (mean ± SE = 8.60 ± 0.26 ng/ml) compared with healthy controls (mean ± SE = 6.27 ± 0.25 ng/ml). Univariate analysis revealed a correlation of sMICB serum concentration with advanced stages of disease (P = 0.009). Only a slight increase in sMICB serum level (P = 0.057) could be observed in regard to the tumor burden. Patients undergoing current treatment with cytostatics (n = 18) revealed a strong increase in sMICB serum level (P < 0.0005), whereas treatment with IFN-α alone or combined with cytostatics (n = 19) showed no change in serum sMICB concentration. According to Kaplan-Meier analysis, elevated sMICB serum levels were associated with a poor overall and a progression-free survival. Multivariate analysis revealed sMICB serum concentration as an independent predictive factor for progression-free and overall survival. Our results show a prognostic relevance of serum sMICB in melanoma patients, indicating that the evaluation of sMICB serum level may be important for the selection of therapeutic strategies.

Increased serum level of thymidine kinase 1 correlates with metastatic site in patients with malignant melanoma.

Thymidine kinase 1 (TK1) is involved in cancer progression. Metastatic site is a prognostic factor in melanoma. We assessed whether serum levels of TK1 are associated with metastatic sites or prognosis in patients treated for stage IV melanoma. The study included 64 patients, who received dacarbazine or four-drug chemotherapy (dacarbazine, vincristine, bleomycin, and lomustine) both combined with interferon-alfa. Serum samples for TK1 were analyzed by ELISA. The patients (n = 22) with only skin and subcutaneous metastases had significantly lower mean TK1 levels (1,639 pg/ml) than the patients (n = 42) with other distant metastases (2,586 pg/ml, Mann-Whitney, p = 0.031). TK1 levels above the median (1,590 pg/ml) were significantly related to deep lymph node involvement (odds ratios 3.672; 95 % confidence intervals 1.024-12.843, p = 0.036). There were no other significant associations between TK1 levels and tumor burden nor were the levels significantly related to the response to therapy or survival. Those eight patients who had received previous adjuvant IFN-alfa therapy had lower mean TK1 levels (1,735 pg/ml) as compared to those 56 patients without previous IFN-alfa therapy (2,338 pg/ml, analysis of variance, p = 0.026). This is the first study exploring serum TK1 in melanoma. TK1 might be involved in the deep lymphatic dissemination and progression of melanoma metastasis.

Roles of sulfonylurea receptor 1 and multidrug resistance protein 1 in modulating insulin secretion in human insulinoma.

BACKGROUND: Sulfonylurea receptor 1 (SUR1) and multidrug resistance protein 1 (MRP1) are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion. METHODS: Fasting glucose, insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma patients. Insulin content, SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence. RESULTS: Insulinoma patients presented the typical demonstrations of Whipple's triad. Fasting glucose of each insulinoma patient was lower than 2.8 mmol/L, and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high glucose. Immunohistochemistry and immunofluorescence staining showed that SUR1 increased, but MRP1 decreased in insulinoma compared with the adjacent islets. CONCLUSIONS: The hypersecretion of insulin in insulinomas might be, at least partially, due to the enrichment of SUR1. In contrast, MRP1, which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.

Characterization of potential antiviral resistance mutations in hepatitis B virus reverse transcriptase sequences in treatment-naïve Chinese patients.

Full-length hepatitis B virus (HBV) reverse transcriptase (RT) sequences were amplified and sequenced among 192 nucleos(t)ide analogue (NA)-naïve Chinese patients with chronic hepatitis B. Deduced amino acids (AAs) at 42 previously reported potential NA resistance (NAr) mutation positions in RT region were analyzed. Patients were found with either B-genotype (28.65%) or C-genotype (71.35%) infections. Rt53, rt91, rt124, rt134, rt221, rt224, rt238 and rt256 were identified as B- and C-genotype-dependent polymorphic AA positions. AA substitutions at 11 classical NAr mutation positions, i.e. rt80, rt169, rt173, rt180, rt181, rt184, rt194, rt202, rt204, rt236 and rt250, were not detected. However, potential NAr mutations were found in 30.73% (59/192) isolates, which involved 18 positions including rt53, rt207, rt229, rt238 and rt256, etc. The concomitant AA changes of HBsAg occurred in 16.67% (32/192) isolates including sG145R mutation. One-third of mutation positions were located in functional RT domains (e.g. rt207 and rt233), A-B interdomains (overlapping HBsAg 'a' determinant and showing most concomitant immune-associated mutations) and non-A-B interdomains (e.g. rt191 and rt213), respectively. Genotypes B and C each showed several preferred positions to mutate. These results might provide insights into understanding the evolution and selection basis of NAr HBV strains under antiviral therapy.

Neurovascular details about forearm muscles: applications in their clinical use in functional muscular transfer.

PURPOSE: The concept of muscle subunits has been introduced for limb reconstruction and functional conservation of donor site, yet it requires thorough understanding of neurovascular anatomy of muscles. The present study provides neurovascular details of forearm skeletal muscles. METHODS: Twenty-eight forearms were dissected totally, ten for observing extramuscular nerve distribution, ten for observing intramuscular nerve distribution by modified Sihler's technique, and the other eight for observing intramuscular artery distribution by aqueous barium sulfate infusion. The forearm muscles were classified into three different types according to Lym's classification. Numbers of extramuscular and intramuscular nerves were counted and compared between the types. Intramuscular vascular distribution was also classified into three different types according to Mathes' method. Intramuscular vascular distribution was compared with nerve distribution as well. RESULTS: There were also some variations in the composition of muscular branches. Numbers of intramuscular nerve branches were significantly higher in muscle types IIa and III. Morphology and intramuscular neurovascular distribution of type II muscles are easy to split into two independent parts for functional muscular flap transfer according to morphology and intramuscular neurovascular distribution. CONCLUSIONS: The present study elucidated that flexor carpi ulnaris and radialis, extensor carpi ulnaris, and carpi radialis brevis were suitable for functional muscular transfer from several different insights, but the roles of pronator teres and supinator remained to be controversial. This study might be very helpful to plastic surgeons and anatomists.

Hyper-excitability in low threshold mechanical A fibers is potentially involved in scorpion BmK sting pain.

In the present study, using the single fiber recording technique, we found that BmK I, the main toxic component in scorpion Buthus martensi Karsch (BmK) venom, induced dramatic increase in excitability of rapidly adapting (RA) and type I slowly adapting (SAI) low threshold mechanical A fibers of rat. Five micrograms BmK I (691 nmol, in 10 microl saline) administrated to the receptive fields induced spontaneous activity in 80% of RA and SAI fibers, increased the response to 10 g-10 s stimulation at about 20 times and altered the firing pattern to burst mode with maximal NS (number of spikes in burst) averaging from all fibers studied as many as 59. The increase in the excitability of RA and SAI fibers did not recover completely in 2h. Our finding suggests that the gigantic abnormal activity in low threshold mechanical A fibers is involved in BmK scorpion sting pain, and the experimental model of BmK scorpion sting pain can be used to study A-fiber related central pathway which is important for relief of refractory neuropathic pain likewise.

[Morphologic observation of the regenerated nerve in reconstructed penis with sensory nerve implantation in rabbit].

OBJECTIVE: To investigate the mechanism of sensory nerve regeneration of the reconstructed penis with sensory nerve implantation and to explore a new surgical technique to improve the postoperative sensory function in phallic reconstruction. METHODS: Adult male New Zealand rabbits were randomly divided into experimental group (n = 20, with sensory nerve implantation) and control group (n = 20, without sensory nerve implantation), which were both performed phalloplasty with a superficial epigastric faciovascular pedicle flap. Postoperatively, the nerve regeneration process of the reconstructed penis was observed histologically. RESULTS: In experimental group, the amount of CGRP positive nerve fibers increased markedly with the time prolonged, whereas merely a few CGRP positive fibers scattered in deep dermis 6 months later in the other group. The cutaneous sensory nerve regeneration of the reconstructed penis in experimental group shows the procedure that the myelinated axon began to exist within 3 months, thereafter the myelinated axon and unmyelinated axon were both observed under the electron microscope. CONCLUSION: These findings show that the rabbit model of phalloplasty with sensory nerve implantation can acquire well sensory reinnervation, and bring a light to clinical application for restoration of sensory function in reconstructed penis.

[A long-term study of regeneration of mechanical sensory fibers after free nerve transplantation to the rabbit reconstructed penis].

OBJECTIVE: To explore the regeneration of mechanical sensory fibers after free nerve transplantation. METHOD: Neuroelectrophysiological technique (single nerve fiber recording) was used to test the regeneration rate of mechanical sensory fibers, the proportion of rapidly and slowly adapting receptors, the stimulating thresholds of regenerated mechanoreceptors and conduction velocity of regenerated fibers. The regeneration pattern of the mechanoreceptors after free nerve transplantation to the rabbit reconstructed penis was also analyzed. RESULTS: 9 months after operation, the number of regenerated mechanical sensory fiber was almost normal. The regenerated rapidly adapting receptors had a higher proportion with higher mature degree than the regenerated slowly adapting receptors. 9 months after nerve transplantation the stimulating thresholds of regenerated mechanoreceptors and conduction velocity of regenerated fibers remained below normal. CONCLUSION: After free nerve transplantation to the rabbit reconstructed penis, the function of both rapidly and slowly adapting sensory nerve fiber partially recovered, but in different extent.

[Electrophysiology research on the spinal nerve source of rabbit penis cutaneous sensation].

OBJECTIVE: To explicate the spinal nerve source of the rabbit penis cutaneous sensation. METHODS: Twelve adult male rabbits were randomly divided into two groups of equal number. While mechanical stimuli were given to the penis by different von Frey hairs, single fiber activities were recorded in vivo in the left (Group A) and right (Group B) S1-S4 spinal nerves, respectively. The mechanical threshold, adaptability and conduction velocity of the fibers were analyzed. RESULTS: When the ipsilateral penis was mechanically stimulated, discharges were detected in S2 and S3 spinal nerve fibers, but not in S1 and S4. The discharge fibers were 39.67 +/- 3.14 (S2) and 21.00 +/- 2.19 (S3) in the left spinal nerve and 40.00 +/- 3.16 (S2) and 19.67 +/- 2.58 (S3) in the right. There was no obvious difference between the numbers of the left spinal nerves and the right ones (P > 0.05). CONCLUSION: The rabbit penis cutaneous sensation originates from S2 and S3 spinal nerves.

[Location of somatic sensory neurons of the skin and dorsal nerve of the penis in rabbits].

OBJECTIVE: To trace the segmental distribution of somatic sensory neurons of the skin and dorsal nerve in the rabbits penis. METHODS: The experiment was performed on 8 adult male rabbits with the nerve tracing method of retrograde axonal transport of horseradish peroxidase (HRP), which was injected into the dermis around the penis and the dorsal nerve of the penis. The rabbits were sacrificed five days later to harvest the spinal cord segments and the dorsal root ganglia of lumbosacral segments for histological study. RESULTS: The HRP tracing showed that a number of labeled HRP positive neurons appeared in spinal ganglia (S2 - S4) in all the rabbits, and distributed segmentally. The counts of the positive neurons different segments were: S2 (215.0 +/- 10.2) , S3 (242.2 +/- 8.3) and S4 (109.7 +/- 8.4) respectively, with statistically significant difference between the two groups. CONCLUSION: The rabbit's sensory nerve fibers in both the skin and the dorsal nerve of the penis are rooted in the S2-S4 segments of spinal ganglia, which distribute regularly.

[Effects of various HIV protease inhibitors on function of rat insulinoma cells].

OBJECTIVE: To investigate the effects of various HIV protease inhibitors on the function of pancreatic beta-cells. METHODS: Rat insulinoma INS-1 cells were incubated with different concentrations of ritonavir or amprenavir for 48 h and stimulated with 20 mmol/L D-glucose for 30 min. The rate of insulin release was measured in the supernatant by ELISA, normalized to cellular DNA contents. Cells were counted with trypan blue and MTT test were determined to evaluate the effect of protease inhibitors on cell viability. RESULT: Ritonavir treatment significantly decreased baseline insulin release and glucose-stimulated insulin release in a dose-dependent manner (r=-0.861, -0.839, both P<0.01). For 10 micromol/L of ritonavir, the decrease rate of baseline insulin secretion and glucose-stimulated insulin secretion was 46% and 47%, respectively. Amprenavir had no effect on the rate of insulin release. CONCLUSION: Various HIV protease inhibitors present different effect on the insulin release of pancreatic beta-cells.