Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

BACKGROUND:With the development of oral implantology,implant restoration has gradually become the first choice of restoration after missing teeth,and bone augmentation procedures have led to the expansion of implant indications and the improvement of the success rate of implant restoration.However,the long-term stability of bone height,width and volume after bone augmentation surgery has been one of the clinical difficulties for oral implantologists.OBJECTIVE:To measure and analyze the bone width,height,and volume of different sites in the bone augmentation area at different time points using cone-beam CT and an automatic image alignment program.METHODS:Seventeen patients with severe bone defects in the upper anterior region who underwent Onlay bone block grafting in the external oblique region were recruited from the Department of Stomatology,Zhejiang Tongde Hospital.There were 10 males and 7 females,with a mean age of(45.88±12.47)years.The cone-beam CT scans of the patients' Onlay bone grafts were taken at five time points:preoperatively,immediately postoperatively,6 months postoperatively,immediately post implantation,and 6 months post implantation,and then were statistically analyzed for alveolar bone volume,width,and height in the bone augmentation area,as well as for the difference in the alveolar bone volume of the bone incremental area between patients of different sexes and age.RESULTS AND CONCLUSION:(1)The alveolar bone volume in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P＜0.05)as well as was higher immediately after bone grafting than 6 months after bone grafting(P＜0.05).The alveolar bone height in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P＜0.05).The horizontal width of the alveolar bone at various sites in the bone augmentation area immediately and 6 months after bone grafting was higher than that before bone grafting(P＜0.05).(2)There was no significant difference in the volume of bone graft resorption at various sites in the bone augmentation area between males and females immediately and 6 months after bone grafting(P＞0.05).Pearson correlation analysis showed a positive correlation between age and the change in bone augmentation area volume immediately and 6 months after bone grafting,but the difference was not statistically significant(P＞0.05).(3)Twenty-five dental implants with completed implant restorations functioned normally,and the survival rate of the implants was 100％.To conclude,Onlay bone graft implant restoration in the upper anterior region can significantly improve insufficient bone with favorable outcomes.However,there is some amount of bone resorption in the bone augmentation area at 6 months after Onlay bone grafting and it is necessary to open up the second surgical area.Clinicians should consider different bone augmentation procedures in accordance with the specific circumstances.

BACKGROUND:With the development of oral implantology,implant restoration has gradually become the first choice of restoration after missing teeth,and bone augmentation procedures have led to the expansion of implant indications and the improvement of the success rate of implant restoration.However,the long-term stability of bone height,width and volume after bone augmentation surgery has been one of the clinical difficulties for oral implantologists.OBJECTIVE:To measure and analyze the bone width,height,and volume of different sites in the bone augmentation area at different time points using cone-beam CT and an automatic image alignment program.METHODS:Seventeen patients with severe bone defects in the upper anterior region who underwent Onlay bone block grafting in the external oblique region were recruited from the Department of Stomatology,Zhejiang Tongde Hospital.There were 10 males and 7 females,with a mean age of(45.88±12.47)years.The cone-beam CT scans of the patients' Onlay bone grafts were taken at five time points:preoperatively,immediately postoperatively,6 months postoperatively,immediately post implantation,and 6 months post implantation,and then were statistically analyzed for alveolar bone volume,width,and height in the bone augmentation area,as well as for the difference in the alveolar bone volume of the bone incremental area between patients of different sexes and age.RESULTS AND CONCLUSION:(1)The alveolar bone volume in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P＜0.05)as well as was higher immediately after bone grafting than 6 months after bone grafting(P＜0.05).The alveolar bone height in the bone augmentation area was higher immediately and 6 months after bone grafting than before bone grafting(P＜0.05).The horizontal width of the alveolar bone at various sites in the bone augmentation area immediately and 6 months after bone grafting was higher than that before bone grafting(P＜0.05).(2)There was no significant difference in the volume of bone graft resorption at various sites in the bone augmentation area between males and females immediately and 6 months after bone grafting(P＞0.05).Pearson correlation analysis showed a positive correlation between age and the change in bone augmentation area volume immediately and 6 months after bone grafting,but the difference was not statistically significant(P＞0.05).(3)Twenty-five dental implants with completed implant restorations functioned normally,and the survival rate of the implants was 100％.To conclude,Onlay bone graft implant restoration in the upper anterior region can significantly improve insufficient bone with favorable outcomes.However,there is some amount of bone resorption in the bone augmentation area at 6 months after Onlay bone grafting and it is necessary to open up the second surgical area.Clinicians should consider different bone augmentation procedures in accordance with the specific circumstances.

In this paper， by consulting the ancient and modern literature， the name， origin， quality evaluation， harvesting and processing， and others of the original animal and medicinal materials of Moschus were systematically sorted out and verified， in order to provide the basis for the development and utilization of the famous classical formulas containing Moschus. According to the textual research， musk deer was first recorded in Shanhaijing. Shennong Bencaojing was recorded as Moschus and all generations were used as the correct name， but there were also aliases such as Shefu， Xiangzhang and Xiangqizi. In ancient times， Moschus berezovskii， M. sifanicus and M. moschiferus were the main sources of Moschus， and the quality of Moschus produced in northwest China was better than that produced in the Yangtze River basin. In modern times， Moschus of M. moschiferus produced in northeast China， M. sifanicus produced in Gansu， Sichuan and other places， and M. berezovskii produced in Ningxia， Shaanxi and other places are regarded as genuine. In ancient times， gunshots， lassoes， arrow shots and other methods were generally used to hunt live musk deer， and the sachets were immediately cut off. Those with high quality were called Xiangshanhuo， and dried in the shade after harvesting， which was known as Maoke Shexiang. Cut open the sachet， remove the shell and dry preservation， commonly known as Moschus kernel. In modern times， the method of taking Moschus from the living body of cultured musk deer is adopted， that is， Moschus kernel is directly taken from its sachet， dried in the shade or dried in a closed dryer. This method realizes the sustainable utilization of Chinese herbal medicine resources， but attention should be paid to the frequency and quality of Moschus. The harvesting time is mostly after the autumnal equinox every year， and before the next summer， it is better to gather sachet in winter. In recent times， it is believed that the shell Moschus is dry， full， thin， elastic， loose inside， many particles， strong and persistent aroma for the best， while the Moschus kernel is particle purple-black， powder yellow-brown， soft and oily texture， strong and persistent aroma for the best. The ancient processing method of Moschus was extracting kernels from the shell. After removing impurities， it is ground and used as medicine. Because its composition is not suitable for heating， the processing method is most common in preparations such as grinding into powder and putting into pills or powders， which has the effect of opening up the orifices and refreshing the mind， and it has continued to this day. Based on the research conclusions， it is suggested that the development of famous classical formulas containing Moschus， M. sifanicus， M. moschiferus and M. berezovskii should be used as the origins. According to the processing requirements specified in the original formula， it should be processed and used as medicine， while those without processing requirements should be used as raw products.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals