Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.

Objective To analyze the stress changes of thoracic vertebra(T)11-sacrum(S)titanium rods in patients with ankylosing spondylitis after vertebral column decancellation(VCD)osteotomy,and provide reference for the selection and improvement of titanium rods before surgery.Methods The original data of the continuous scanning tomographic images of patients with ankylosing spondylitis after VCD osteotomy were imported into Mimics 21.0 in DICOM format,and T11-S vertebrae,screws and titanium rods were respectively reconstructed.They were imported into 3-Matic to establish a preliminary geometric modeling,and then processed with noise removal,paving,smoothing,etc.The improved model was imported into Hypermesh 10 software for grid division,and the material was imported into ANSYS 19.2 to display the finite element model after attribute assignment,Set the boundary and load conditions,and measure the stress value at the connection between the screw and the titanium rod.Results Under neutral position,forward bending,lateral bending,and axial rotation conditions,the titanium rod had the highest stress at the upper vertebrae(T11)and the lowest stress at the top vertebrae(L3);Under the backward extension condition,the titanium rod has the highest stress at the lower end vertebra(L5).Conclusion In the upper and lower vertebrae,it is possible to consider increasing the diameter of the titanium rod,enhancing its hardness,or changing it to a double rod.

Objective To establish a normal three-dimensional model of the hip bone in adolescents aged 10-19 years old,analyze the morphology and positional parameters of the posterior superior iliac spine of the hip bone among different genders,sides,and ages,which can supplement the study of the anatomical morphology of the hip bone and to provide a reference for the diagnosis of the clinically relevant diseases and for the therapeutic manipulation and localization of the hip bone.Methods Forty adolescent patients aged 10-19 years without previous spinal pelvic diseases were selected,and the pelvic CT image data were collected and imported into Mimics 21.0 software to establish the model.The relative position parameters of the posterior superior iliac spine and the surrounding anatomical landmarks included the length from the posterior superior iliac spine to the anterior superior iliac spine(ab),the length from the tip of the posterior superior iliac spine to the sciatica(ac),the length from the tip of the posterior superior iliac spine to the pubic tubercle(ae),the length from the tip of the posterior superior iliac spine to the midpoint of the posterior margin of the auricular joint surfaces(af),the length from the tip of the posterior superior iliac spine to the iliac spine turn(ag),and the length from the sciatica tubercle to the highest point of the iliac spine(cd).The local parameters of the posterior superior iliac spine included the width(W0)and the thickness(H0)at point A.The maximum width of the posterior iliac spine(WMAX),its distance from point a(D0),and the width of the iliac spine were measured at 0.5,1,and 1.5 cm from point a,and were recorded sequentially as W1,W2,and W3.The width of the iliac spine at the turn of the iliac spine(point g)was measured(W4).The relative positions and parameters of the posterior superior iliac spine to the surrounding anatomical landmarks and the localized parameters of the posterior superior iliac spine were compared sequentially for different genders,sides,and age groups.Results In the measurement result of the parameters of the posterior superior iliac spine and the surrounding anatomical landmarks,the differences in the comparisons between different genders of the ac,ae,and af indexes were statistically significant(P＜0.05),and the differences in the comparisons between different genders of the ab,ag,and cd indexes were not statistically significant(P＞0.05).The differences in the comparisons between the right and left sides of the ab,ac,ae,af,ag,and cd indexes were not statistically significant(P＞0.05).The difference in comparison between different age groups of ab,ac,ae,af,ag,and cd indicators was statistically significant(P＜0.05).In the measurement result of the local parameters of the posterior superior iliac spine,the difference in the comparison between the sexes of the W0,W1,W2,WMAX,and H0 indexes was statistically significant(P＜0.05),and the difference in the comparison between the sexes of the W3,W4,and D0 indexes was not statistically significant(P＞0.05);And the difference in the comparison between the left and right sides of the W0,W1,W2,and the right and left sides of the W3,W4,WMAX,D0,and H0 indexes was not statistically significant(P＞0.05);The difference between W0,W1,W2,W3,W4,WMAX,D0,H0 indicators compared between different age groups was not statistically significant(P＞0.05).Conclusion Adolescent females have overall greater pelvic parameters than males,with wider and thicker tips of the posterior superior iliac spine in females and narrower and thinner tips of the posterior superior iliac spine in males;Pelvic parameters show a tendency to increase with age,while the width and thickness of the posterior superior iliac spine,as well as the width of the cephalic end to the iliac spine remain essentially unchanged.

The Compound Cheqian Tablets are derived from Cheqian Power in Comprehensive Recording of Divine Assistance, and they are made by modern technology with the combination of Plantago asiatica and Coptis chinensis. To investigate the material basis of Compound Cheqian Tablets in the treatment of diabetic nephropathy, in this study, the chemical components of Compound Cheqian Tablets were characterized and analyzed by UPLC-Q-TOF-MS/MS, and a total of 48 chemical components were identified. The identified chemical compounds were analyzed by network pharmacology. By validating with previous literature, six bioactive compounds including acteoside, isoacteoside, coptisine, magnoflorine, palmatine, and berberine were confirmed as the index components for qua-lity evaluation. Furthermore, the content of the six components in the Compound Cheqian Tablets was determined by the "double external standards" quantitative analysis of multi-components by single marker(QAMS), and the relative correction factor of isoacteoside was calculated as 1.118 by using acteoside as the control; the relative correction factors of magnoflorine, palmatine, and berberine were calculated as 0.729, 1.065, and 1.126, respectively, by using coptisine as the control, indicating that the established method had excellent stability under different conditions. The results obtained by the "double external standards" QAMS approximated those obtained by the external standard method. This study qualitatively characterized the chemical components in the Compound Cheqian Tablets by applying UPLC-Q-TOF-MS/MS and screened the pharmacodynamic substance basis for the treatment of diabetic nephropathy via network pharmacology, and primary pharmacodynamic substance groups were quantitatively analyzed by the "double external stan-dards" QAMS method, which provided a scientific basis for clarifying the pharmacodynamic substance basis and quality control of Compound Cheqian Tablets.
Humans ; Tandem Mass Spectrometry ; Berberine/pharmacology* ; Chromatography, High Pressure Liquid/methods* ; Network Pharmacology ; Diabetic Nephropathies ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Tablets

OBJECTIVE: To study the effect of ultrasound-guided fascia iliaca compartment block on perioperative analgesia and postoperative complications in geriatric patients with hip fractures. METHODS: A total of 127 elderly patients undergoing hip fracture surgery from January 2021 to September 2021 were randomized to receive ultrasound-guided continuous fascia iliaca compartment block(group F) either intravenous analgesia control group(group C). There were 62 cases in group F, including 19 males and 43 females with an average age of (82.4±7.2) years old ranging from 66 to 95 years old, involving 25 femoral neck fractures and 37 femoral intertrochanteric fractures. There were 65 cases in control group, including 18 males and 47 females, with an average age of (81.4±8.7) years old ranging from 65 to 94 years old, involving 29 femoral neck fractures and 36 femoral intertrochanteric fractures. The visual analogue scale(VAS), minimental state examination (MMSE), observer's assessment of alertness/sedation(OAA/S) scale, modified Bromage score, postoperative complications and general conditions during hospitalization in two groups were observed. RESULTS: The resting and exercise VAS at 30 min after block, anesthesia placement and 6, 24 and 48 h after surgery were lower than those in group C(P<0.05). In group F, MMSE scores at 12 h before surgery, and 1, 3 d after surgery and OAA/S scores at 3 d after surgery were higher than those in group C(P<0.05). The incidence of adverse effects and the number requiring additional analgesia were lower than those in group C(P<0.05). Group F had better perioperative analgesia satisfaction and hospital stay than group C(P<0.05). But there was no significant difference regarding Bromage score and 30-day mortality between two group(P>0.05). CONCLUSION Ultrasound-guided continuous fascia iliacus space block was safe and effective for elderly patients with hip fracture, and could significantly reduce perioperative pain, improve postoperative cognitive function, and reduce postoperative complications, thereby shortening hospital stay and improving the quality of life during hospitalization.
Male ; Female ; Humans ; Aged ; Aged, 80 and over ; Pain Management ; Nerve Block ; Quality of Life ; Hip Fractures/surgery* ; Pain/surgery* ; Femoral Neck Fractures/surgery* ; Femoral Fractures/surgery* ; Ultrasonography, Interventional ; Postoperative Complications/surgery* ; Fascia ; Pain, Postoperative

BACKGROUND: The molecular mechanisms of heart failure (HF) are still poorly understood. Circular RNA (circRNA) has been discovered in the heart in increasing numbers of studies. The goal of this research is to learn more about the potential roles of circRNAs in HF. METHODS & RESULTS: We used RNA sequencing data to identify the characteristics of circRNAs expressed in the heart and discovered that the majority of circRNAs screened were less than 2000 nt. Additionally, chromosomes One and Y had the most and least number of circRNAs, respectively. After excluding duplicate host genes and intergenic circRNAs, a total of 238 differentially expressed circRNAs (DECs) and 203 host genes were discovered. However, only four of the 203 host genes of DECs were examined in HF differentially expressed genes. Another study used Gene Oncology analysis of DECs host genes to elucidate the underlying pathogenesis of HF, and it found that binding and catalytic activity accounted for a large portion of DECs. Immune system, metabolism, and signal transduction pathways were significantly enriched. Furthermore, 1052 potentially regulated miRNAs from the top 40 DECs were collected to build a circRNA-miRNA network, and it was discovered that 470 miRNAs can be regulated by multiple circRNAs, while others are regulated by a single circRNA. In addition, a comparison of the top 10 mRNAs in HF and their targeted miRNAs revealed that DDX3Y and UTY were regulated by the most and least circRNA, respectively. CONCLUSION These findings demonstrated circRNAs have species and tissue specific expression patterns; while circRNA expression is independent on host genes, the same types of genes in DECs and DEGs worked in HF. Our findings would contribute to a better understanding of the critical roles of circRNAs and lay the groundwork for future studies of HF molecular functions.

Objective: To grasp the epidemiological characteristics of influenza outbreaks in Guangdong Province by analyzing the outbreaks of influenza-like cases reported in Guangdong Province from January 2015 to the end of August 2022. Methods: In response to the outbreak of epidemics in Guangdong Province from 2015 to 2022, information on on-site epidemic control was collected, and epidemiological analysis was conducted to describe the characteristics of the epidemics. The factors that influence the intensity and duration of the outbreak were determined through a logistic regression model. Results: A total of 1 901 influenza outbreaks were reported in Guangdong Province, with an overall incidence of 2.05%. Most outbreak reports occurred from November to January of the following year (50.24%, 955/1 901) and from April to June (29.88%, 568/1 901). A total of 59.23% (1 126/1 901) of the outbreaks were reported in the Pearl River Delta region, and primary and secondary schools were the main places where outbreaks occurred (88.01%, 1 673/1 901). Outbreaks with 10-29 cases were the most common (66.18%, 1 258/1 901), and most outbreaks lasted less than seven days (50.93%,906/1 779). The size of the outbreak was related to the nursery school (aOR=0.38, 95%CI:0.15-0.93), the Pearl River Delta region (aOR=0.60, 95%CI:0.44-0.83), the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=3.01, 95%CI:1.84-4.90), the influenza A(H1N1) (aOR=2.02, 95%CI:1.15-3.55) and the influenza B (Yamagata) (aOR=2.94, 95%CI: 1.50-5.76). The duration of outbreaks was related to school closures (aOR=0.65, 95%CI: 0.47-0.89), the Pearl River Delta region (aOR=0.65, 95%CI: 0.50-0.83) and the time interval between the onset of the first case and the time of report (>7 days compared with ≤3 days: aOR=13.33, 95%CI: 8.80-20.19; 4-7 days compared with ≤3 days: aOR=2.56, 95%CI: 1.81-3.61). Conclusions: An influenza outbreak in Guangdong Province exhibits two peaks, one in the winter and spring seasons and the other in the summer. Primary and secondary schools are high-risk areas, and early reporting of outbreaks is critical for controlling influenza outbreaks in schools. Furthermore, comprehensive measures should be taken to prevent the spread of the epidemic.
Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/epidemiology* ; Disease Outbreaks ; Epidemics ; China/epidemiology*

Objectives: To analyze the long-term survival of patients with localized renal cell carcinoma after partical nephrectomy. Methods: The clinicopathological records and survival follow-up data of 2 046 patients with localized renal cell carcinoma, who were treated with partial nephrectomy from August 2001 to February 2021 in the Department of Urology, Sun Yat-sen University Cancer Center, were retrospectively analyzed. There were 1 402 males and 644 females, aged (M(IQR)) 51 (19) years (range: 6 to 86 years). The primary end point of this study was cancer-specific survival. Survival curves were estimated using the Kaplan-Meier method, and the difference test was performed by Log-rank test. Univariate and multivariate Cox analysis were fitted to determine factors associated with cancer-specific survival. Results: The follow-up time was 49.2 (48.0) months (range: 1 to 229 months), with 1 974 patients surviving and 72 dying. The median cancer-specific survival time has not yet been reached. The 5- and 10-year cancer specific survival rates were 97.0% and 91.2%, respectively. The 10-year cancer-specific survival rates for stage pT1a (n=1 447), pT1b (n=523) and pT2 (n=58) were 95.3%, 81.8%, and 81.7%, respectively. The 10-year cancer-specific survival rates of patients with nuclear grade 1 (n=226), 2 (n=1 244) and 3 to 4 (n=278) were 96.6%, 89.4%, and 85.5%, respectively. There were no significant differences in 5-year cancer-specific survival rates among patients underwent open, laparoscopic, or robotic surgery (96.7% vs. 97.1% vs. 97.5%, P=0.600). Multivariate analysis showed that age≥50 years (HR=3.93, 95%CI: 1.82 to 8.47, P<0.01), T stage (T1b vs. T1a: HR=3.31, 95%CI: 1.83 to 5.99, P<0.01; T2+T3 vs. T1a: HR=2.88, 95%CI: 1.00 to 8.28, P=0.049) and nuclear grade (G3 to 4 vs. G1: HR=2.81, 95%CI: 1.01 to 7.82, P=0.048) were independent prognostic factors of localized renal cell carcinoma after partial nephrectomy. Conclusions: The long-term cancer-specific survival rates of patients with localized renal cancer after partial nephrectomy are satisfactory. The type of operation (open, laparoscopic, or robotic) has no significant effect on survival. However, patients with older age, higher nuclear grade, and higher T stage have a lower cancer-specific survival rate. Grasping surgical indications, attaching importance to preoperative evaluation, perioperative management, and postoperative follow-up, could benefit achieving satisfactory long-term survival.

Objective: To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. Methods: A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. Results: A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all P<0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% CI: 0.716-0.823) vs 0.674 (95% CI: 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all P<0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (P<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: HR=4.33, 95% CI: 3.22-5.81, P<0.001; high-risk group vs low-risk group: HR=11.95, 95% CI: 8.29-17.24, P<0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (HR=2.63, 95% CI: 1.88-3.68, P<0.001). Conclusions: Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.
Humans ; Nomograms ; Retrospective Studies ; Carcinoma, Renal Cell/pathology* ; Prognosis ; Risk Factors ; Nephrectomy ; Kidney Neoplasms/pathology* ; Necrosis

Femoral acetabular impingement (FAI) syndrome is a motion-related clinical disorder of the hip joint, resulting in cartilage lesions frequently. The pattern and natural history of these cartilage lesions vary with types of FAI, each bearing unique gross appearance and injury mechanism. On the basis of available evidence, this paper reviews the progress of the FAI-related acetabular cartilage lesions in pathogenesis, diagnosis and treatment. Cam-type FAI is always closely associated with acetabular cartilage lesions and early-onset of hip osteoarthritis. However, the reason why acetabular cartilage developed into osteoarthritis in FAI of Cam-type is unknown. In addition to the direct mechanical impingement and the vulnerable anatomic base of chondrolabral junction, stress change from abnormal movement or anatomical morphology will lead to the change of biomechanical environment, causing a chronic-recurrent inflammation in articular cartilage. The preoperative diagnosis of acetabular cartilage lesions depends on a triad of symptoms, clinical signs and imaging findings. 1.5 T magnetic resonance arthrography and 3.0 T magnetic resonance imaging are equally valued in objectively diagnosing cartilage lesions. Final diagnosis relies on surgical exploration, however, there is no consensus on how cartilage lesions should be reported, including the description of extent, location, pattern and grade. Using Beck classification of clock-face method to describe lesions observed in surgery is recommended at present. Most treatment methods of FAI-related acetabular cartilage lesions are borrowed from treating cartilage lesions in knee joints. Conservative treatment includes rest, activity modification, nonsteroidal anti-inflammatory medications and physical therapy. Surgery is an option if conservative treatment of at least 6 months fails. The surgical procedures commonly include chondroplasty, microfracture and enhanced microfracture, autologous matrix-induced chondrogenesis, autologous chondrocyte implantation, matrix-induced autologous chondrocyte implantation, osteochondral transplantation and other cartilage repair techniques. However, there is no consensus on the standardized treatment of FAI-related acetabular cartilage lesions for lacking evidence-based guidance currently.