Objective To evaluate the bioequivalence of two formulations of minocycline hydrochloride capsules administered orally after fasting administration and fed administration.Methods An open-label,randomized,two-period,self-crossover design was employed to assess the bioequivalence study.Twenty-eight healthy subjects were enrolled in both fasting and fed groups,with each period involving a single administration of either the reference formulation or the test formulation of 50 mg,separated by a washout period of 7 days.The concentration of minocycline in human plasma was determined by HPLC-MS/MS and was used for calculating pharmacokinetic parameters and evaluating the bioequivalence of the test formulation and reference formulation.Results After oral administration of test and reference formulations of minocycline under fasting condition,the Cmax Values of minocycline were(541±137)ng·mL-1 for the test formulation and(558±140)ng·mL-1for the reference formulation.The AUC0-t values were(8 347±1 986)h·ng·mL-1 for the test and(8 205±1 790)h·ng·mL-1 for the reference.The t1/2 values were(18.2±2.84)h for the test and(18.0±3.05)h for the reference.After oral administration of the test and reference formulations of minocycline under fed condition,the Cmax values of minocycline were(349±72.1)ng·mL-1 for the test and(352±73.2)ng·mL-1for the reference.The AUC0-twere(6 428±1 077)h·ng·mL-1 for the test and(6 588±1 118)h·ng·mL-1 for the reference.The t1/2values were(18.5±3.10)h for the test and(18.4±3.21)h for the reference.Under fasting condition,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test and reference formulations were(90.84%,101.46% ),(95.2%,102.8% ),and(95.31%,102.71% ),respectively.Under fed conditions,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test formulation and the reference formulation were(94.71%,103.42% ),(95.40%,99.83% ),and(95.79%,100.02% ),respectively.Conclusions Bioequivalence of the two minocycline formulations was demonstrated after fasting administration and fed administration in a healthy Chinese population.

Objective:To compare the efficacy and safety of robotic surgery and open surgery in the treatment of hilar cholangiocarcinoma.Methods:PubMed, Embase, Cochrane Library, Web of Science, CNKI and Wanfang database were searched to compare the treatment of hilar cholangiocarcinoma by robotic surgery and traditional open surgery. Literatures were searched from the establishment of the database to July 2023. Compare operation time, intraoperative blood transfusion rate, R 0 resection rate, lymph node metastasis rate, postoperative complication rate and hospital stays between the two groups. The combined odds ratio ( OR) and mean difference ( MD) and 95% confidence interval (95% CI) were calculated using RevMan 5.4 software. Results:A total of 4 studies were included, including 267 patients with hilar cholangiocarcinoma. There were 177 males and 90 females, aged (58.8±5.7) years. A total of 267 patients were divided into open surgery group ( n=165) and robotic surgery group ( n=102) according to the surgical formula. The extract results show: operative time ( MD=-103.96, 95% CI: -216.90-8.98, P=0.070) and intraoperative blood transfusion rate ( OR=1.32, 95% CI: 0.43-4.07, P=0.630), R 0 resection rate ( OR=1.41, 95% CI: 0.71-2.81, P=0.330), lymph node metastasis rate ( OR=1.62, 95% CI: 0.46-5.63, P=0.450), postoperative complications ( OR=0.60, 95% CI: 0.28-1.31, P=0.200), and postoperative hospital stay ( MD=2.17, 95% CI: -11.56-15.90, P=0.760). Conclusion:In the treatment of hilar cholangiocarcinoma, robotic surgery is as safe and feasible as open surgery. However, due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

【Objective】 To improve the understanding and diagnosis and treatment level of ALK negative anaplastic large cell lymphoma (ALK-ALCL) by sharing the diagnosis and treatment process of a patient with ALK-ALCL treated in Hangzhou Bay Hospital of Ningbo. 【Methods】 The clinical data and diagnosis and treatment process of the patient were retrospectively analyzed, and relevant literature was reviewed. 【Results】 The patient was a young male, with recurrent gross hematuria and right low back pain as the initial symptoms.Imaging examination indicated bladder tumor.After resection, the tumor was reduced and confirmed to be ALK-ALCL.After chemotherapy and autologous hematopoietic stem cell transplantation, the patient’s condition continued to improve.During the follow-up, no recurrence was observed. 【Conclusion】 Primary ALK-ALCL in the bladder is very rare and prone to misdiagnosis and missed diagnosis in clinical practice.The successful diagnosis and treatment experience of this patient can provide clinical reference.

Objective:To investigate the effect of vitamin D supplementation on weight loss efficacy and insulin resistance (IR) in obese patients.Methods:It was a randomized controlled trial. A total of 190 obese patients with vitamin D deficiency were selected from the obesity clinic of Tianjin Union Medical Center from March to December in 2023. The patients were divided into control group (95 cases) and vitamin D group (95 cases) according to random number table. The control group was given energy-limited high-protein diet combined with moderate intensity exercise, and the vitamin D group was supplemented with vitamin D on the basis of the control group, 14 000 U/week for 24 weeks. A total of 25 dropped out of the study from the two groups for various reasons. Finally, 79 cases in the control group and 86 cases in the vitamin D group were included in the analysis. Independent sample t test and rank sum test were used to compare serum 25 hydroxyvitamin D [25 (OH) D] level, body weight, body mass index, fat mass, visceral fat area, fasting blood glucose, fasting insulin and glycated hemoglobin (HbA 1c) between the two groups at baseline and after intervention. Homeostasis model insulin resistance index (HOMA-IR) was used to evaluate the degree of insulin resistance (IR), and the effects of vitamin D supplementation on weight loss efficiency and IR in those patients were analyzed. Results:There was no significant differences in serum 25(OH)D level between the two groups before intervention ( P>0.05); the serum 25(OH)D level in the vitamin D group was significantly higher than that in the control group after intervention [(30.90±7.55) vs (16.00±4.34) μg/L] ( t=-15.35, P<0.001). The body weight, body mass index, fat mass, visceral fat area, fasting blood glucose, fasting insulin, HbA 1c, and HOMA-IR were all significantly lower after the intervention than those before the intervention in both groups [control group: (93.32±13.47) vs (98.95±14.31) kg, (33.74±5.09) vs (35.80±5.52) kg/m 2, (39.77±11.87) vs (44.12±12.79) kg, (183.76±40.95) vs (204.01±32.18) m 2, 5.00 (4.55, 5.67) vs 5.24 (4.68, 6.42) mmol/L, 16.78 (13.94, 24.30) vs 22.56 (15.95, 31.2) mU/L, 5.55%±0.53% vs 6.05%±0.99%, 4.11 (3.14, 5.57) vs 5.51 (3.61, 8.49); vitamin D group: (88.14±17.66) vs (104.43±22.02) kg, (31.02±5.10) vs (36.66±5.98) kg/m 2, (35.51±12.87) vs (46.67±13.33) kg, (166.50±49.50) vs (213.64±40.14) m 2, 4.70 (4.35, 5.07) vs 5.17 (4.77, 6.30) mmol/L, 13.18 (9.87, 18.84) vs 21.67 (15.78. 32.74) mU/L, 5.43%±0.48% vs 6.21%±1.22%, 2.88 (1.99, 4.21) vs 5.19 (3.82, 9.27)], and the body weight, body mass index, adiposity, visceral fat area, fasting blood glucose, fasting insulin, and HOMA-IR were all significantly lower in vitamin D group than those in the control group [(88.14±17.66) vs (93.32±13.47) kg, (31.02±5.10) vs (33.74±5.09) kg/m 2, (35.51±12.87) vs (39.77±11.87) kg, (166.50±49.50) vs (183.76±40.95) m 2, 4.70 (4.35, 5.07) vs 5.00 (4.55, 5.67) mmol/L, 13.18 (9.87, 18.84) vs 16.78 (13.94, 24.30) mU/L, and 2.88 (1.99, 4.21) vs 4.11 (3.14, 5.57), respectivley] (all P<0.05). The IR remission rate was significantly higher in the vitamin D group than that in the control group after the intervention (37.3% vs 15.3%) ( χ2=8.071, P=0.002). Conclusion:Supplementation of vitamin D on the basis of energy-limited high-protein diet combined with moderate intensity exercise can significantly improve the efficacy of weight loss and IR in obese patients with vitamin D deficiency.

Objective:To analyze the risk factors for 6-month prognosis of traumatic spinal cord injury (TSCI).Methods:A retrospective analysis was conducted of the 133 patients with TSCI who had been admitted to Department of Orthopaedics, The First Hospital Affiliated to Jinan University from January 2017 to August 2021. The patients with TSCI were categorized into an improved group ( n=82) and a non-improved group ( n=51) according to the improvements in the American Spinal Injury Association (ASIA) grading between admission and 6 months after injury. To identify the risk factors that might affect the prognosis of TSCI patients at 6 months after injury, univariate and logistic regression analyses were conducted of indicators such as gender, age, length of MRI spinal cord signal change, maximum canal compromise (MCC), maximum spinal cord compression (MSCC), brain and spinal cord injury center(BASIC)score, neutrophil-to-lymphocyte ratio (NLR) within 3 days after injury, ASIA grading within 3 days after injury, mean arterial pressure (MAP) at 3 days after operation, and presence of complications. Results:The univariate analysis showed significant differences between the improved and non-improved groups in length of MRI spinal cord signal change, MCC, MSCC, BASIC, NLR within 3 days after injury, ASIA grading within 3 days after injury, MAP at 3 days after operation, and presence of complications (all P<0.05). The logistic regression analysis showed that NLR ( OR=0.463, 95% CI: 0.287 to 0.748, P=0.002) and ASIA grading ( OR=11.684, 95% CI: 1.684 to 81.086, P=0.013) within 3 days after injury, as well as MAP at 3 days after operation ( OR=2.224, 95% CI: 1.306 to 3.787, P=0.003), were risk factors affecting the 6-month prognosis in TSCI patients. Conclusion:The NLR and ASIA grading within 3 days after injury, and MAP at 3 days after operation are risk factors that may affect the prognosis of TSCI patients at 6 months after injury.

Endosomal TLRs (TLR3/7/8/9) are highly analogous innate immunity sensors for various viral or bacterial RNA/DNA molecular patterns. Among them, TLR7, in particular, has been suggested to be a target for various inflammatory disorders and autoimmune diseases including systemic lupus erythematosus (SLE); but few small-molecule inhibitors with elaborated mechanism have been reported in literature. Here, we reported a well-characterized human TLR7-specific small-molecule inhibitor, TH-407b, with promising potency and negligible cytotoxicity through a novel binding mechanism. Notably, TH-407b not only effectively inhibited TLR7-mediated pro-inflammatory signaling in a variety of cultured cell lines but also demonstrated potent inflammation suppressing activities in primary peripheral blood mononuclear cells (PBMCs) derived from SLE patients. Furthermore, TH-407b showed prominent efficacy in vivo, improved survival rate and ameliorated symptoms of SLE model mice. To obtain molecular insights into the TH-407b derivatives' inhibition mechanism, we performed the structural analysis of TLR7/TH-407b complex using cryogenic electron microscopy (cryo-EM) method. As an atomistic resolution cryo-EM structure of the TLR family, it not only of value to facilitate structure-based drug design, but also shed light to methodology development of small proteins using EM. Significantly, TH-407b has unveiled an inhibition strategy for TLR7 via stabilizing its resting/inactivated state. Such a resting state could be generally applicable to all TLRs, rendering a useful method for targeting this group of important immunological receptors.

Objective:To construct a new model for assessing insulin resistance(IR) in newly diagnosed type 2 diabetic patients by combining anthropometry parameters and biochemical parameters.Methods:A total of 677 newly diagnosed type 2 diabetic patients were included in this study. Clinical data, biochemical indicators, and body composition measurements were collected, and a predictive model was constructed using logistic regression analysis.Results:The IR prediction model was constructed based on five indicators: triglycerides(TG), fasting plasma glucose(FPG), visceral fat area(VFA), alanine aminotransferase(ALT), and uric acid(UA). The formula for the new predictive model was as follows: y=-17.765+ 1.389×ln VFA+ 1.045×ln UA+ 0.91×ln ALT+ 2.167×ln FPG+ 0.805×ln TG. The receiver operating characteristic curve(ROC) area under the curve(AUC) for the model was 0.82, with an optimal cutoff value of 1.67, sensitivity of 0.80, and specificity of 0.71. The AUC values for the triglyceride glucose(TyG) index, lipid accumulation product(LAP), and triglyceride/high-density lipoprotein cholesterol ratio(THR) were 0.75, 0.75, and 0.70, respectively. The corresponding sensitivities were 0.66, 0.84, and 0.71, and the specificities were 0.71, 0.59, and 0.60. The optimal cutoff values were 1.81, 30.31, and 1.14, respectively. Conclusion:The new model constructed using TG, FPG, VFA, ALT, and UA as indicators showed high predictive value and can serve as a new model for assessing IR in newly diagnosed type 2 diabetic patients.

Objective:To investigate the clinical efficacy and safety of phacoemulsification and intraocular lens (IOL) implantation combined with a modified iris cerclage for cataract with mydriasis.Methods:A clinical retrospective study was conducted. Six eyes of 6 patients with cataract and mydriasis were treated with phacoemulsification and IOL implantation combined with modified iris cerclage in Department of Ophthalmology, the Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, from January 2018 to September 2022. The best corrected visual acuity (BCVA), intraocular pressure (IOP), corneal endothelial cell count (CECC), pupil diameter and photophobia scores were statistically analysed by paired sample t test at 3 days before surgery and 3 months after surgery. The pupil shape, IOL position, intraoperative and postoperative complications were observed. P<0.05 was considered statistically significant. Results:Postoperative follow-up with all patients lasted 3 to 6 months. The BCVA at the final follow-up (0.73±0.16) was significantly improved in all 6 patients compared with that of before surgery (0.43±0.12), with statistically significant difference ( P<0.05). There was no significant difference in IOP and CECC before and after surgery ( P>0.05). The pupil diameter after surgery was significantly smaller than that before surgery ( P<0.05). The postoperative photophobia score was significantly lower than that before surgery ( P<0.05). Pupils in all 6 eyes were round-like, in a central position and without an iris capture of IOL. There was no serious intraoperative or postoperative complication. Conclusion:Phacoemulsification and IOL implantation combined with modified iris cerclage is a safe and efficient procedure that can effectively improve the visual acuity, reduce the pupil diameter, improve photophobia symptom and enhance the visual quality in patients with cataract combined with mydriasis.

Objective To evaluate the effect of different techniques of hepatic artery reconstruction on postoperative hepatic artery complications and clinical prognosis in liver transplantation. Methods Clinical data of 140 liver transplant recipients were retrospectively analyzed. All recipients were divided into the conventional hepatic artery reconstruction group (n=123) and special hepatic artery reconstruction group (n=17) according to hepatic artery reconstruction methods. Intraoperative and postoperative clinical indexes, the incidence of postoperative hepatic artery complications and survival rate were compared between two groups. Results The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at postoperative 1 d, total bilirubin (TB) at postoperative 7 d and prothrombin time international normalized ratio (PT-INR) at postoperative 30 d in special hepatic artery reconstruction group were higher than those in conventional hepatic artery reconstruction group, and the differences were statistically significant (all P < 0.05). There were no significant differences in the operation time, anhepatic phase, intraoperative blood loss, intraoperative transfusion volume of red blood cells, cold or warm ischemia time, the length of intensive care unit (ICU) stay, the length of hospital stay and postoperative blood flow of liver allograft between two groups (all P > 0.05). In the conventional hepatic artery reconstruction group, 5 recipients developed hepatic artery complications, whereas no hepatic artery complications occurred in the special hepatic artery reconstruction group, with no significant difference between two groups (P > 0.05). In the special hepatic artery reconstruction group, the 1-, 3- and 5-year cumulative survival rates were equally 82.4%, compared with 85.0%, 78.9% and 75.6% in the conventional hepatic artery reconstruction group, respectively. There was no significant difference between two groups (all P > 0.05). Conclusions When hepatic artery variations and (or) lesions are detected in donors and recipients, use of special hepatic artery reconstruction may effectively restore the hepatic arterial blood flow of liver allograft after liver transplantation, and will not affect the incidence of hepatic artery complications and survival rate of the recipients following liver transplantation.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*