Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective:To explore the safety, effectiveness, and short-term outcomes of transoral robotic surgery (TORS) for supraglottic laryngeal cancer.Methods:A retrospective analysis was conducted on patients with supraglottic laryngeal cancer who underwent TORS at Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Eye Ear Nose and Throat Hospital of Fudan University, and the First Affiliated Hospital of China Medical University between January 2018 and April 2024. Data on operative time, intraoperative blood loss, postoperative hospital stay, perioperative tracheostomy, nasogastric feeding, complications, and short-term follow-up were analyzed. Statistical analysis was performed using Python.Results:A total of 27 patients with supraglottic laryngeal cancer were included from the four centers, including 24 males and 3 females, with a median age of 66 (65, 68) years [ M( Q1, Q3), same below]. There were 26 cases of squamous cell carcinoma and 1 case of adenoid cystic carcinoma.The TNM staging included T1 in 10 cases (37.04%), T2 in 13 cases (48.15%), and T3 in 4 cases (14.81%); N0 in 14 cases (51.85%), N1 in 7 cases (25.93%), and N2 in 6 cases (22.22%). The Da Vinci Si system was used in 23 cases, and the Da Vinci Xi in 4 cases. The robotic surgical time was 53 (30, 58) min. Concurrent neck dissection was performed in 25 cases, neoadjuvant therapy was given preoperatively in 8 cases (29.63%), and postoperative radiotherapy was administered in 13 cases (48.15%). Tracheostomy was performed in 11 cases (40.74%). Nasogastric tube placement was required in 23 cases (85.19%), with a median duration of 16 (12, 21) days. The postoperative hospital stay was 9.19±4.07 days. The median follow-up time was 12 (3, 30) months. Local recurrence occurred in 2 cases. The 3-year overall survival rate was 100%, and the 3-year disease-free survival rate was 94.1%. Conclusion:With appropriate patient selection, TORS for supraglottic laryngeal cancer demonstrates satisfactory short-term outcomes, thereby offering advantages in safety, efficacy, and minimal invasiveness, which can be considered a new treatment option for this condition.

Objective:To explore the safety, effectiveness, and short-term outcomes of transoral robotic surgery (TORS) for supraglottic laryngeal cancer.Methods:A retrospective analysis was conducted on patients with supraglottic laryngeal cancer who underwent TORS at Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Eye Ear Nose and Throat Hospital of Fudan University, and the First Affiliated Hospital of China Medical University between January 2018 and April 2024. Data on operative time, intraoperative blood loss, postoperative hospital stay, perioperative tracheostomy, nasogastric feeding, complications, and short-term follow-up were analyzed. Statistical analysis was performed using Python.Results:A total of 27 patients with supraglottic laryngeal cancer were included from the four centers, including 24 males and 3 females, with a median age of 66 (65, 68) years [ M( Q1, Q3), same below]. There were 26 cases of squamous cell carcinoma and 1 case of adenoid cystic carcinoma.The TNM staging included T1 in 10 cases (37.04%), T2 in 13 cases (48.15%), and T3 in 4 cases (14.81%); N0 in 14 cases (51.85%), N1 in 7 cases (25.93%), and N2 in 6 cases (22.22%). The Da Vinci Si system was used in 23 cases, and the Da Vinci Xi in 4 cases. The robotic surgical time was 53 (30, 58) min. Concurrent neck dissection was performed in 25 cases, neoadjuvant therapy was given preoperatively in 8 cases (29.63%), and postoperative radiotherapy was administered in 13 cases (48.15%). Tracheostomy was performed in 11 cases (40.74%). Nasogastric tube placement was required in 23 cases (85.19%), with a median duration of 16 (12, 21) days. The postoperative hospital stay was 9.19±4.07 days. The median follow-up time was 12 (3, 30) months. Local recurrence occurred in 2 cases. The 3-year overall survival rate was 100%, and the 3-year disease-free survival rate was 94.1%. Conclusion:With appropriate patient selection, TORS for supraglottic laryngeal cancer demonstrates satisfactory short-term outcomes, thereby offering advantages in safety, efficacy, and minimal invasiveness, which can be considered a new treatment option for this condition.

Abstract: To investigate the in vitro release, in vivo pharmacokinetics, and the in vitro-in vivo correlation of progesterone suspension injection, self-made progesterone suspension injection was taken as an example. The in vitro release curves of three different particle sizes of progesterone suspension injections were measured using paddle method and dialysis bag method. The in vivo pharmacokinetic characteristics of self-made progesterone suspension injection was studied on SD rats. The plasma concentration of self-made progesterone preparation was detected after intramuscular injection, and correlated with the in vitro release profiles obtained by the dialysis bag method after processing by Wagner-Nelson method. The results showed that when the in vitro release of three different particle sizes of progesterone suspension injections was measured by the paddle method, more than 85% was rapidly released within 20 min, while 85% cumulative release was reached at 40 h, 84 h and 120 h by dialysis bag method, respectively. The release rate obtained by the dialysis bag method was basically consistent with the in vivo release trend, with a correlation coefficient of >0.95, indicating a strong in vivo and in vitro correlation. This study provides some reference for the establishment of the in vitro and in vivo correlation of long-acting suspension injection.

Objective:To analyze the problems and risk factors of the investigator initiated out-of-range trial, propose countermeasures and suggestions, and provide reference for improving project standardization and quality, and preventing research risks.Methods:Through literature analysis and field research, combined with personal work experience, this study sorted and analyzed the problems in the regulation of out-of-range IIT conducted in hospital, and proposed countermeasures.Results:Through analysis, it was found that the current out-of-range IIT trial in China faces 5 problems: imperfect management regulations, incomplete IIT management organizational system in medical institutions, insufficient scientificity of research protocols, insufficient ethical review, and insufficient research funds.Conclusions:Out-of-range IIT is of great significance in promoting pharmaceutical innovation. Standardized management of such projects requires the efforts of regulatory authorities, medical institutions, and ethics committees, as well as the continuous improvement of researchers' awareness and research capabilities to promote the orderly, high-quality, and rapid development of IIT. Based on the above analysis, this article proposed countermeasures and suggestions: at the national level, summarize practical experience from various regions as soon as possible, improve IIT management regulations and technical guidelines; establishing clinical research and design guidance departments in medical institutions and strengthening scientific review; the ethics committee formulates ethical review standards and processes for out-of-range IIT projects to enhance review capabilities; establish a normalized clinical research training mechanism in hospitals; expand and standardize the channels for IIT funding.

Objective:To explore the application effect of group guidance based on intelligent communication matrix in patients with type 2 diabetes mellitus (T2DM) .Methods:Using the convenient sampling method, a total of 60 T2DM patients with poor self-management ability who scored less than 19.6 on Summary of Diabetes Self Care Activities (SDSCA) in the Affiliated Chuzhou Hospital of Anhui Medical University were selected as the research objects from May to June 2020. They were randomly divide into the observation group ( n=30) and the control group ( n=30). The observation group was given continuous group guidance based on intelligent communication matrix, while the control group was given routine health guidance. The SDSCA score, body mass index and glycosylated hemoglobin (HbA1c) before and after intervention were compared between the two groups. Results:After intervention, the SDSCA score of the observation group was higher than that of the control group, HbA1c was lower than that of the control group and body mass index was lower than that of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The group guidance based on intelligent communication matrix can improve the self-management level of T2DM patients and reduce their body mass index and HbA1c levels, which has clinical application value.

Objective:To evaluate the application value of extended latissimusdorsi musculocutaneous flap combined with breast precision hand in stage Ⅰ breast reconstruction.Methods:Twelve cases of extended latissimusdorsi musculocutaneous flap combined with stage Ⅰ breast reconstruction for breast cancer precision surgery were collected from January 2022 to February 2023 in our department, the postoperative complications of surgical techniques were analyzed, and the cosmetic effects of breast reconstruction were evaluated according to Harris standards.Results:All 12 cases underwent breast reconstruction with extended latissimusdorsi musculocutaneous flap, and the survival rate of the flap was 100%. There was local cutaneous margin necrosis in 1 case of back incision, partial ischemic necrosis of the nipple in 1 case, and effusion in the donor area of the back in 5 cases. Harris evaluation of cosmetic effect of breast reconstruction was excellent in 3 cases, good in 6 cases, and fair in 3 cases. Follow-up time was 4-16 months (median was 12 months), and no local recurrence or distant metastasis was observed during follow-up.Conclusions:The extended latissimusdorsi musculocutaneous flap combined with precision mastectomy stage Ⅰ reconstruction is a safe and feasible treatment method for breast cancer.

In recent years, artificial intelligence (AI) and oncology are rapidly integrated and developed, gradually moving towards clinical application. In China, the incidence and mortality of gastric cancer rank first among various tumors. The development of AI technologies such as convolutional neural network, narrow-band imaging magnifying endoscope, full-field digital section and survival circulation network has the potential to be applied to early screening, auxiliary diagnosis, pathological diagnosis, prognosis analysis, as well as individualized diagnosis and treatment process of gastric cancer. However, AI medical treatment still has many problems such as insufficient data sample size and difficulty in integration. Reasonable design and application of AI technology is expected to provide more scientific and accurate diagnosis and treatment for patients with gastric cancer, improve the overall survival rate and quality of life of patients with gastric cancer, and achieve more breakthroughs in the medical field.