OBJECTIVE To optimize the water extraction process of Flos Lonicerae-Fructus Forsythuae and determine the range of water extraction process parameters.METHODS The active components were screened by network pharmacology,and the indica-tor ingredients were determined in combination with the quality markers under the relevant terms of Chinese Pharmacopoeia 2020 edition and the literature.Take extraction yield and the extraction rate of the indicative component as the critical quality attributes of the water extraction process to screen critical process parameters.The mathematical model was established by Box-Behnken experimental design to investigate the interaction between CQAs and CPPs and build the design space of the water extraction process of Flos Lonicerae-Fruc-tus Forsythuae.RESULTS The extraction percentages of phenolic acids,forsythoside A and forsythin were screened as the index components;specifications of medicinal slices,extraction time and water addition were the key process parameters.Based on the estab-lishment and optimization of the design space,the optimum water extraction process was obtained as follows:the medicinal slice of Lian-Qiao was broken into 0.8-1.2 cm,adding 12 times the amount of water in the first and extract for 30-50 min,10 times the a-mount of water in the second and extract for 25-30 min.CONCLUSION The verification results show that the measured value ob-tained by using the design space method to optimize the water extraction process is close to the predicted value,indicating that the method is stable and reliable,which can provide ideas for its further process development and quality control for the couple medicines of Flos Lonicerae-Fructus Forsythuae.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of T-cell lymphoma. Despite the scarcity of reported BIA-ALCL cases in Asia, it is imperative to research early diagnosis. The crucial diagnostic criteria for BIA-ALCL include the presence of ALK - and CD30 + T cells exceeding 10% in the delayed seroma fluid. Furthermore, laboratory tests, such as histological examination of capsulectomies and analysis of clonal T-cell receptor (TCR) gene rearrangements, serve as important auxiliary diagnostic indicators. This article reported the case of a 56-year-old female patient who underwent bilateral breast augmentation with implants over 20 years ago. She presented with hardness, enlargement, and mild discomfort in her left breast. She was admitted to Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine in January 2023. MRI suggested implant rupture. Therefore, bilateral implant removal surgery was performed on February 2, 2023. Pathological examination of the fluid within the capsule of the left implant revealed a small number of ALK - and CD30 + T cells, with monoclonality observed in TCRγ gene rearrangement, indicating early changes suggestive of BIA-ALCL. Long-term follow-up is needed. The authors suggest that patients suspected of BIA-ALCL should undergo TCR gene rearrangement testing in addition to cytological and immunological examinations, which can provide guidance for the diagnosis, treatment, and necessary long-term follow-up of these patients.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of T-cell lymphoma. Despite the scarcity of reported BIA-ALCL cases in Asia, it is imperative to research early diagnosis. The crucial diagnostic criteria for BIA-ALCL include the presence of ALK - and CD30 + T cells exceeding 10% in the delayed seroma fluid. Furthermore, laboratory tests, such as histological examination of capsulectomies and analysis of clonal T-cell receptor (TCR) gene rearrangements, serve as important auxiliary diagnostic indicators. This article reported the case of a 56-year-old female patient who underwent bilateral breast augmentation with implants over 20 years ago. She presented with hardness, enlargement, and mild discomfort in her left breast. She was admitted to Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine in January 2023. MRI suggested implant rupture. Therefore, bilateral implant removal surgery was performed on February 2, 2023. Pathological examination of the fluid within the capsule of the left implant revealed a small number of ALK - and CD30 + T cells, with monoclonality observed in TCRγ gene rearrangement, indicating early changes suggestive of BIA-ALCL. Long-term follow-up is needed. The authors suggest that patients suspected of BIA-ALCL should undergo TCR gene rearrangement testing in addition to cytological and immunological examinations, which can provide guidance for the diagnosis, treatment, and necessary long-term follow-up of these patients.

Objective To observe the effects of acute normovolemic hemodilution(ANH)on target-controlled infusion(TCI)of etomidate blood drug concentration and adrenal cortical function.Methods Sixty patients who undergo elective multisegmental spine surgery,35 males and 25 females,aged 30-60 years,BMI 20-25 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups using random number table method:ANH group and control group,30 patients in each group.Both groups used a target-controlled infusion of etomidate for anesthesia induction and anesthesia maintenance.In the ANH group,ANH was performed after steady anesthesia induction,ideal Hct 28％to 30％,and transfused within 1 hour after surgery;the control group was routinely treated.The dosage of etomidate was recorded.Liquid chroma-tography-tandem mass spectrometry(LC-MS/MS)was used to detect etomidate blood concentrations at the immediate postoperative,10,20,and 30 minutes postoperative periods in the two groups,and the immedi-ate moment autologous blood collected into the storage bag,preserved in the storage bag for 1 hour,and the immediate moment transfused back in the ANH group.Plasma concentrations of cortisol(Cor),adrenocorti-cotropic hormone(ACTH),and aldosterone(ALD)were measured by chemiluminescence immunoassay(CLIA)before the induction of anesthesia,immediately after the operation,and at 1 day and 2 days postop-eratively.Results There was no significant difference in the total dosage of etomidate between the two groups.Compared with the immediate postoperative period,the plasma etomidate concentration was signifi-cantly decreased 10,20,and 30 minutes after surgery(P<0.05).Compared with the control group,the concentration increased significantly 10 minutes after surgery in the ANH group(P<0.05).The plasma concentrations of etomidate were(547.8±119.4)ng/ml at the immediate moment autologous blood collected into the storage bag,(536.7±107.8)ng/ml at the preserved in the storage bag for 1 hour,and(522.8±91.7)ng/ml at theimmediatemoment transfusedbackinthe ANHgroup.Comparedwithbeforein-duction of anesthesia,the concentration of Cor and ALD immediately after the operation decreased signifi-cantly(P<0.05)and the concentration of ACTH was significantly higher(P<0.05).There were no sta-tistically significant differences in the concentrations of Cor,ALD,and ACTH between the two groups before induction of anesthesia 1 day and 2 days postoperatively.Conclusion In the orthopedic surgery of TCI eto-midate,return transfusion of collected autologous blood transiently(about 10 minutes)increases etomidate blood concentrations,the function of adrenal cortical will recover to the preoperative level within 24 hours after the operation.

Objective:To investigate the application value of virtual reality laparoscopic simulator training in laparoscopic transabdominal preperitoneal hernioplasty (TAPP).Methods:The prospective cohort study was conducted. Twenty young physicians from The First Affiliated Hospital of Harbin Medical University with ≥3 years of clinical experience in general surgery and no foundation in laparoscopy were selected for training during July to August 2023. Physicians were divided into two groups based on random number table method. Physicians undergoing virtual reality laparoscopic simulator training were divided into the virtual reality group, and physicians undergoing regular laparoscopic simulator training were divided into the regular group. Two groups of physicians were trained using laparoscopic simulator for 10 days (2 hours for each skill, with a total of 6 hours per day for 3 skills), and the training covered basic laparoscopic surgical skills such as clamping, cutting and suturing and knotting. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups were conducted using the independent sample t test and the paired ttest was used for intra group comparison. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups were conducted using the chi-square test. Results:(1) Physicians situation before training. A total of 20 physicians were selected for eligibility. There were 13 males and 7 females, aged 31(range, 30?34)years. There are 7 males and 3 females in the virtual reality group, with age of (31.5±1.4)years and the TAPP simulation surgery time of (42±4)minutes before training. There are 6 male and 4 female students in the regular group, with age of (31.2±1.0)years and the TAPP simulation surgery time of (42±4)minutes before training. There was no significant difference in gender, age, TAPP simulation surgery time between the two groups of physicians ( P>0.05), confounding bias ensured comparability. (2) Basic skills of physicians before and after training. For physicians in the virtual reality group, the clamping score was 5.1±1.0, the cutting score was 4.9±1.0, the suturing and knotting score was 4.7±1.5 before training. The clamping score was 8.0±1.3, the cutting score was 7.9±1.5, the suturing and knotting score was 6.6±1.3 after training. There were significant differences in the above indicators before and after training ( t=?5.75, ?5.21, ?3.07, P<0.05). For physicians in the regular group, the clamping score was 5.3±1.0, the cutting score was 5.0±1.2, the suturing and knotting score was 4.3±1.5 before training. The clamping score was 7.1±1.2, the cutting score was 6.7±1.3, the suturing and knotting score was 5.7±1.1 after training. There were significant differences in the above indicators before and after training ( t=?3.73, ?3.16, ?2.42, P<0.05). (3) Completion of simulated surgical situations before and after training. The time of completing TAPP simulation surgery for virtual reality group after training was (29±3)minutes, versus (42±4)minutes before training, showing a significant difference before and after training ( t=7.69, P<0.05). The time of completing TAPP simulation surgery for regular group after training was (36±4)minutes, versus (42±4)minutes before training, showing a significant difference before and after training ( t=3.75, P<0.05). The time of completing TAPP simulation surgery of virtual reality group after training was shorter than that of regular group, showing a significant difference between the two groups ( t=?3.89, P<0.05). Conclusion:Both of virtual reality and regular laparoscopic simulator can enhance the basic laparoscopic surgical skills and the proficiency of TAPP simulation surgery of physicians, and the training effect of virtual reality laparoscopic simulators is better.

Objective To evaluate the effectiveness and safety of different Chinese patent medicine in improving blood lipid and microcirculation in coronary heart disease patients with phlegm-blood stasis syndrome based on network meta-analysis.Methods The randomized controlled trials(RCTs)of different Chinese patent medicine in the treatment of blood lipid and microcirculation in coronary heart disease patients with phlegm-blood stasis syndrome were collected by searching CNKI,Wanfang,VIP,SinoMed,PubMed,EMbase,Cochrane Library,and Web of science databases from the establishment of the database to April 3,2023.Literature quality evaluation and network meta-analysis were conducted using Review Manager 5.4 and Stata15.1 software.Results Thirty-seven RCTs were included,with a total sample size of 4 064 cases,involving 15 different Chinese patent medicines.The network meta-analysis showed that the efficacy of Chinese patent medicine combined with conventional Western medicine is often better than that of conventional Western medicine alone.There are no serious adverse reactions.The top three Chinese patent medicines with cumulative probability of total clinical efficacy were Guanmai Zaitong soft extract,Gualoupi Injection and Quyu Xiaoban Capsule.In terms of improving triglyceride(TG)and low-density lipoprotein(LDL-C),the top three Chinese patent medicines were Gualoupi Injection,Huxinkang Tablet and Guanxin Shutong Capsule.In terms of improving plasma viscosity and fibrinogen,the top three Chinese patent medicines were Ginkgo Damo Injection,Gualoupi Injection and Guanxin Shutong Capsule.In terms of improving endothelial function[nitric oxide(NO)and endothelin-1(ET-1)],the top three Chinese patent medicines were Ginkgo Damo Injection,Danlou Tablet and Tongmai Yuxin Pill.In terms of reducing inflammation hypersensitivity C-reactive protein(hs-CRP),the top three Chinese patent medicines were Ginkgo Damo Injection,Huxinkang Tablet and Guanxin Shutong Capsule.Conclusion The current evidence shows that the combination of TCM,which is used for the treatment of phlegm-blood stasis syndrome,with conventional Western medicine in the treatment of coronary heart disease has advantages in improving clinical efficacy,blood lipids and microcirculation.TCM especially for the treatment of phlegm-blood stasis syndrome shows more obvious advantage,such as Guanmai Zaitong soft extract and Gualoupi injection,which can be taken into consideration as part of the clinical guidelines.However,due to the limited number and quality of the included literatures,the research results still need to be verified by more high-quality,multi-center,double-blind randomized trials.The purpose is to provide more reliable evidence-based medical reference.

PiT2 is an inorganic phosphate (Pi) transporter whose mutations are linked to primary familial brain calcification (PFBC). PiT2 mainly consists of two ProDom (PD) domains and a large intracellular loop region (loop7). The PD domains are crucial for the Pi transport, but the role of PiT2-loop7 remains unclear. In PFBC patients, mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion. To date, six missense mutations have been identified in PiT2-loop7; however, the mechanisms by which these mutations cause PFBC are poorly understood. Here, we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2. Furthermore, we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase (AMPK)- or protein kinase B (AKT)-mediated PiT2 phosphorylation. In contrast, the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities. These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2. This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.
Humans ; Cell Membrane ; Mutation, Missense ; Phosphates/metabolism* ; Sodium-Phosphate Cotransporter Proteins, Type III/genetics*

Objective:To evaluate the clinical efficacy of modified all-arthroscopic reconstruction of medial patella femoral ligament (MPFL) for the treatment of recurrent patellar dislocation.Methods:A retrospective case series study was conducted to analyze the clinical data of 38 patients (46 knees) with recurrent patellar dislocation, who were treated at First Affiliated Hospital of Shenzhen University from January 2017 to January 2020. The patients included 12 males (12 knees) and 26 females (34 knees), aged 14-40 years [(24.6±5.4)years]. All patients underwent the modified all-arthroscopic MPFL reconstruction procedure. The femoral tunnel locations were assessed by 3D-CT immediately after surgery. The MRI was performed at 6 and 12 months after operation to assess the healing morphology of the reconstructed MPFL. The Lysholm score and Kujala score were used to assess the knee function before operation, at 6 months after operation, at 12 months after operation and at the last follow-up. The time to return to sports as well as complications were observed.Results:All patients were followed up for 26-48 months [(32.4±8.6)months]. Postoperative 3D-CT examination showed that the femoral tunnels were located in the groove area of the medial epicondyle of the femur and the adductor tubercle. At 6 and 12 months after operation, MRI T2 images showed that the reconstructed MPFL had a low signal and well tensioned ligament tissue, indicating that the MPFL was healed well. The Lysholm scores at 6 and 12 months postoperatively and at the last follow-up were (81.1±12.0)points, (91.2±3.8)points, and (92.2±9.8)points, respectively, being significantly higher than the preoperative (52.4±10.6)points (all P<0.01). The Kujala scores at 6 and 12 months postoperatively and at the last follow-up were (85.4±3.9)points, (91.4±3.6)points, and (93.1±8.5)points, respectively, being significantly higher than the preoperative (55.2±6.8)points (all P<0.01). Compared with 6 months postoperatively, the Lysholm score and Kujala score were significantly improved at 12 months postoperatively and at the last follow-up (all P<0.05). All patients returned to sports, with the time to return to sports for 3-12 months [(8.7±2.3)months] after operation. One patient had poor wound healing but was healed after dressing changes. No wound infection, nerve injury, joint stiffness, patella re-dislocation or other complications occurred. Conclusion:For recurrent patellar dislocation, the modified all-arthroscopic MPFL reconstruction has advantages of accurate bone tunnel positioning, good ligament healing, good function recovery, early return to sports, and less postoperative complications.

Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.

Rice stripe virus (RSV) transmitted by the small brown planthopper causes severe rice yield losses in Asian countries. Although viral nuclear entry promotes viral replication in host cells, whether this phenomenon occurs in vector cells remains unknown. Therefore, in this study, we systematically evaluated the presence and roles of RSV in the nuclei of vector insect cells. We observed that the nucleocapsid protein (NP) and viral genomic RNAs were partially transported into vector cell nuclei by utilizing the importin α nuclear transport system. When blocking NP nuclear localization, cytoplasmic RSV accumulation significantly increased. In the vector cell nuclei, NP bound the transcription factor YY1 and affected its positive regulation to FAIM. Subsequently, decreased FAIM expression triggered an antiviral caspase-dependent apoptotic reaction. Our results reveal that viral nuclear entry induces completely different immune effects in vector and host cells, providing new insights into the balance between viral load and the immunity pressure in vector insects.
Animals ; Cell Nucleus ; Hemiptera/metabolism* ; Insect Vectors/genetics* ; Insecta ; Nucleocapsid Proteins/metabolism* ; Oryza ; Plant Diseases ; Tenuivirus/metabolism* ; Virus Replication