Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

Yinyang Gongji Pills have the effects of strengthening the body resistance to eliminate pathogenic factors, removing stasis, and reducing swelling, which is a commonly used traditional Chinese medicine(TCM) formula for treating intestinal accumulation. A real-world, registered, and single-arm clinical trial was conducted to observe the clinical efficacy and safety of Yinyang Gongji Pills combined with capecitabine in the treatment of advanced colorectal cancer and analyze the clinical characteristics of the patients. A total of 60 patients with advanced colorectal cancer who refused or could not tolerate standard treatment of western medicine were included in the study. They were treated with Yinyang Gongji Pills combined with capecitabine until disease progression or intolerable adverse events occurred. The main observation indicators were progression-free survival(PFS) and safety. The treatment effects of the patients under different baseline characteristics were analyzed. The clinical trial has found that the median PFS of all enrolled patients was 7.3 months, with 30.1% of patients having a PFS exceeding 12.0 months. Layered analysis showed that the median PFS of patients with the onset site being the colon and rectum were respectively 8.4 and 4.7 months. The median PFS of patients with high, medium, and low tumor burden were respectively 7.0, 4.7, and 10.8 months. The median PFS of patients with wild-type and mutant-type RAS/BRAF were respectively 7.9 and 6.9 months. The median PFS of patients with KPS scores ≥80 and ≤70 were respectively 7.9 and 6.5 months. The median PFS of patients treated with Yinyang Gongji Pills for ≥6, 3-6, and ≤3 months were respectively 8.0, 5.2, and 4.2 months. The median PFS of patients with spleen, kidney, liver, and lung syndrome differentiation in TCM were respectively 8.3, 6.7, 7.3, and 5.6 months. The median PFS of patients with TCM pathological factors including phlegm, dampness, and blood stasis were respectively 7.0, 7.3, and 6.5 months. Common adverse reactions include anemia, decreased white blood cells, decreased appetite, fatigue, and hand foot syndrome, with incidence rates being respectively 44.2%, 34.6%, 42.3%, 32.7%, and 17.3%. The results showed that the combination of Yinyang Gongji Pills and capecitabine demonstrated potential clinical efficacy and good safety in this study. The patients have clinical characteristics such as low tumor burden, onset site at the colon, KPS scores ≥ 80, long duration of oral TCM, and TCM syndrome differentiation including spleen or liver.
Humans ; Capecitabine/adverse effects* ; Colorectal Neoplasms/mortality* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Middle Aged ; Female ; Aged ; Adult ; Treatment Outcome

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

Objective To investigate the clinical efficacy of percutaneous closure of foramen ovale guided by transthoracic echocardio-graphy with simply delivery sheath.Methods The clinical data of patients with patent foramen ovale underwent interventional closure and percutaneous closure guided by transthoracic echocardiography with simply delivery sheath in our hospital from January 2020 to December 2022 were analyzed retrospectively,the patients were divided into interventional closure group(40 cases)and simply delivery sheath group(39 cases).The operation time,incidence of surgical complications,and surgical success rates of patients in the two groups were compared.The closure effect were evaluated by ultrasound immediately after surgery.All the patients were followed up for 6 months after surgery to evaluate remission of the symptoms.Results The surgical success rate of simply delivery sheath group(100%)was higher than that of interventional closure group(90.0%),with statistically significant difference(P<0.05).The operation time of simply delivery sheath group was longer than that of interventional closure group,with statistically significant difference(P<0.05).One patient in the interventional closure group had small amount of pericardial effusion during the operation.Two patients had decreased blood pressure and slowed heart rate in simply delivery sheath group,and symptoms disappeared after treatment.There was no significant difference in the incidence of complications between the two groups(P>0.05).After 6-month follow-up,all occluders were in good position and no residual leakage was found.The symptoms of headache or dizziness disappeared in 28 patients in interventional closure group,significantly relieved in 8 patients;the symptoms of headache or dizziness disappeared in 30 patients in simply delivery sheath group,and significantly relieved in 9 patients.Conclusion Percutaneous closure for patent foramen ovale under the guidence of transthoracic echocardiography with simply delivery sheath is safe and feasible with satisfactory efficacy and higher successful rate without radiation hazard.It is worthy of clinical promotion.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: To investigate the safety and efficacy of pelvic peritoneal reconstruction and its effect on anal function in laparoscopy-assisted anterior resection of low and middle rectal cancer. Methods: A prospective cohort study was conducted. Consecutive patients with low and middle rectal cancer who underwent laparoscopy-assisted transabdominal anterior resection at Naval Military Medical University Changhai Hospital from February 2020 to February 2021 were enrolled. Inclusion criteria: (1) the distance from tumor to the anal verge ≤10 cm; (2) laparoscopy-assisted transabdominal anterior resection of rectal cancer; (3) complete clinical data; (4) rectal adenocarcinoma diagnosed by postoperative pathology. Exclusion criteria: (1) emergency surgery; (2) patients with a history of anal dysfunction or anal surgery; (3) preoperative diagnosis of distant (liver, lung) metastasis; (4) intestinal obstruction; (5) conversion to open surgery for various reasons. The pelvic floor was reconstructed using SXMD1B405 (Stratafix helical PGA-PCL, Ethicon). The first needle was sutured from the left anterior wall of the neorectum to the right. Insertion of the needle was continued to suture the root of the sigmoid mesentery while the Hemo-lok was used to fix the suture. The second needle was started from the beginning of the first needle, after 3-4 needles, a drainage tube was inserted through the left lower abdominal trocar to the presacral space. Then, the left peritoneal incision of the descending colon was sutured, after which Hemo-lok fixation was performed. The operative time, perioperative complications, postoperative Wexner anal function score and low anterior resection syndrome (LARS) score were compared between the study group and the control group. Three to six months after the operation, pelvic MRI was performed to observe and compare the pelvic floor anatomical structure of the two groups. Results: A total of 230 patients were enrolled, including 58 who underwent pelvic floor peritoneum reconstruction as the study group and 172 who did not undergo pelvic floor peritoneum reconstruction as the control group. There were no significant differences in general data between the two groups (all P>0.05). The operation time of the study group was longer than that of control group [(177.5±33.0) minutes vs. (148.7±45.5) minutes, P<0.001]. There was no significant difference in the incidence of perioperative complications (including anastomotic leakage, anastomotic bleeding, postoperative pneumonia, urinary tract infection, deep vein thrombosis, and intestinal obstruction) between the two groups (all P>0.05). Eight cases had anastomotic leakage, of whom 2 cases (3.4%) in the study group were discharged after conservative treatment, 5 cases (2.9%) of other 6 cases (3.5%) in the control group were discharged after the secondary surgical treatment. The Wexner score and LARS score were 3.1±2.8 and 23.0 (16.0-28.0) in the study group, which were lower than those in the control group [4.7±3.4 and 27.0 (18.0-32.0)], and the differences were statistically significant (t=-3.018, P=0.003 and Z=-2.257, P=0.024). Severe LARS was 16.5% (7/45) in study group and 35.5% (50/141) in control group, and the difference was no significant differences (Z=4.373, P=0.373). Pelvic MRI examination 3 to 6 months after surgery showed that the incidence of intestinal accumulation in the pelvic floor was 9.1% (3/33) in study group and 46.4% (64/138) in control group (χ(2)=15.537, P<0.001). Conclusion: Pelvic peritoneal reconstruction using stratafix in laparoscopic anterior resection of middle and low rectal cancer is safe and feasible, which may reduce the probability of the secondary operation in patients with anastomotic leakage and significantly improve postoperative anal function.
Anastomotic Leak/surgery* ; Humans ; Intestinal Obstruction/surgery* ; Laparoscopy ; Postoperative Complications/surgery* ; Prospective Studies ; Rectal Diseases/surgery* ; Rectal Neoplasms/surgery* ; Retrospective Studies ; Syndrome ; Treatment Outcome

This study discusses the effect of Biyanning Granules on local symptoms and systemic immune function of patients with chronic rhinosinusitis with nasal polyps(CRSwNP) within the 6 months of treatment by glucocorticoid nasal spray after surgical treatment. To be specific, a total of 237 CRSwNP patients, treated in Otorhinolaryngology Head and Neck Surgery in Shanxi Bethune Hospital, were enrolled. All patients were treated by nasal endoscopy and classified into hormone group(Budesonide Nasal Spray after surgery), Chinese medicine group(Biyanning Granules after surgery), and combination group(Budesonide Nasal Spray+Biyanning Granules after surgery) with random number table method, 79 cases in each group, and the treatment lasted 3 months. The follow-up was performed from the day of discharge to 12 months after the surgery. The clinical effect was observed. The visual analogue scale(VAS) scores and sino-nasal outcome test-20(SNOT-20) scale scores were used to assess patient's subjective symptoms and quality of life. Lund-Kennedy endoscopic score(LKES), Japanese T&T olfactometry, and standard olfactory test were used to evaluate the objective curative effect on patients. The levels of interleukin(IL)-21, CD4~+CD25~+Foxp3~+Treg, and CD4~+Th17 in peripheral blood were analyzed. The incidence of complications, recurrence rate, and adverse reactions during treatment were also recorded. The total effective rate after treatment in the combination group was higher than that in the hormone group and Chinese medicine group(P<0.05). VAS scores and SNOT-20 scale scores were lower in the three groups after treatment than before treatment and lower in the combination group than in the other two groups(P<0.05). The improvement in LKES and T&T standard olfactometry test was better in the combination group than in the other two groups(P<0.05). Serum levels of IL-21 and CD4~+Th17 in the three groups were lower than before treatment. The levels in the combination group were lower than those in the other two groups and lower in the hormone group than in the Chinese medicine group(P<0.05). Serum CD4~+CD25~+Foxp3~+Treg level was higher in the three groups after treatment than before, higher in the combination group than in the other two groups, and higher in the Chinese medicine group than in the hormone group(P<0.05). During the treatment, no serious adverse reactions were observed. After treatment, the combination group showed no significant difference in the incidence and recurrence rate of complications from the hormone group and Chinese medicine group. In the treatment of CRSwNP with glucocorticoid, Biyanning Granules reduced the side effects of glucocorticoid and assisted glucocorticoid in alleviating the symptoms of patients. It significantly improved the curative effect, regulated immune imbalance, accele-rated the recovery of immune function, reduced the recurrence rate of inflammatory reaction, and improved the quality of life. The combination of Chinese and western treatment is more effective than glucocorticoid alone and warrants further clinical study in large sample size.
Budesonide/therapeutic use* ; Chronic Disease ; Forkhead Transcription Factors/metabolism* ; Glucocorticoids/therapeutic use* ; Humans ; Immunity ; Medicine, Chinese Traditional ; Nasal Sprays ; Quality of Life ; Rhinitis/surgery* ; Sinusitis/surgery*

Objective:To investigate the clinical characteristics of hepatitis-associated aplastic anaemia(HAAA)in children.Methods:A retrospective analysis was performed on the clinical manifestations, laboratory examinations, treatments and other clinical data of five children with aplastic anemia(AA)diagnosed by bone marrow examination after admission with acute liver dysfunction admitted to the Department of Gastroenterology, Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2016 to December 2020.Results:All five children were boys and the onset age of these children ranged from 2 to 13 years.All of the five cases were acute onset and presented with jaundice.The time frame of the diagnosis of HAAA was 0 to 12 weeks from the presentation of the liver disease.One patient had simultaneous onset of hepatitis and aplastic anemia.The liver function was significantly improved at the diagnosis of HAAA in three patients and worsen in one patient.Only one patient showed CMV-DNA positive and the pathogen results of other patients were negative.Lymphocyte immunity disorders were found in all five patients, and the proportion of inhibitory/cytotoxic T lymphocytes(CD3 + CD8 + ) increased.Two children received hematopoietic stem cell transplantation, of which one died and one improved after transplantation.One child improved after treated with antithymocyteglobulin and cyclosporin.One child died due to severe infection.There was no significant improvement in one child treated with cyclosporine. Conclusion:HAAA should be alerted in acute hepatitis patients.Blood routine should be monitored even if liver function improves.Bone marrow tests are needed if patients have peripheral cytopenia in two or more lineages.Early and timely treatments with immunosuppressive therapy and hematopoietic stem cell transplantation can improve the prognosis.

Short-term intermittent fasting (IF) is beneficial to weight control in patients with nonalcoholic fatty liver disease, but the impact of long-term IF is not clear. In this study, healthy C57BL/6N mice with 4-month alternate day fasting (ADF) were used to study the effects of long-term IF on systemic and liver lipid metabolism. The results showed that, compared with the Ad Libitum group, the weight and food conversion rate of mice in the ADF group were markedly decreased and increased respectively, and the liver index and the liver content of triglyceride were significantly increased by pathological examination. qRT-PCR analysis revealed that the mRNA expression of the lipogenesis gene Pparγ and lipolysis gene Atgl was up-regulated in the ADF group (P < 0.05). Western blot analysis showed that the ratio of microtubule associated protein LC3-II/LC3-I was increased, while the abundance of autophagy adaptor protein p62 was decreased in the ADF group. In addition, autophagy signal positive regulation key factor AMPK phosphorylation was increased (P < 0.05), and negative regulation factor mTOR phosphorylation was decreased (P < 0.05) in the ADF group, indicating that hepatocyte autophagy activity was elevated. Taken together, ADF for 4 months results in an excessive liver triglyceride accumulation, accompanied by a marked decrease in liver mTOR phosphorylation and a significant increase in hepatic autophagy.
Mice ; Animals ; Intermittent Fasting ; Mice, Inbred C57BL ; Liver/pathology* ; TOR Serine-Threonine Kinases ; Lipid Metabolism ; Autophagy ; Triglycerides