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.

Objective To preliminarily investigate the safety and efficacy of donor pancreas needle biopsy in simultaneous pancreas-kidney transplantation. Methods Clinical data of 7 cases undergoing donor pancreas biopsy were collected retrospectively. All cases underwent donor pancreas biopsy before or during simultaneous pancreas-kidney transplantation. Frozen section or paraffin sectioning techniques were used for tissue preparation, and hematoxylin-eosin and Masson staining were performed to histologically evaluate the donor pancreas. The quality of donor pancreas was comprehensively assessed by combining histological findings with the donor's clinical data. Postoperative follow-up data of 5 simultaneous pancreas-kidney transplant recipients were collected to summarize the safety of donor pancreas biopsy and the prognosis of transplant recipients. Results The 7 pancreas donors were aged 28 to 62 years, with a body mass index ranging from 20.76 to 27.68 kg/m². Liver ultrasound indicated fatty liver in 3 cases, while pancreatic ultrasound did not reveal any significant abnormalities. Among them, biopsy was performed on 2 donors after completion of pancreatic procurement and processing, and the frozen section histology showed moderate acute pancreatitis changes (edema of acinar cells, necrosis and inflammatory cell infiltration). Combined with a serum amylase level elevated more than 3 times the upper limit of normal value, these two donor pancreases were finally discarded. The remaining 5 cases underwent biopsy immediately after pancreatic vascular anastomosis during simultaneous pancreas-kidney transplantation, and histological evaluation was performed on paraffin-embedded sections. No biopsy-related complications (such as bleeding, pancreatic fistula, etc.) occurred after transplantation. One recipient died of severe infection 2 months after transplantation, while the other 4 recipients were followed up for more than 5 years, with well-functioning transplant kidneys and pancreases. Conclusions Donor pancreas biopsy is relatively safe, and the risk of biopsy-related complications after transplantation is controllable. Comprehensive assessment of donor pancreas quality by combining histological evaluation with the donor's clinical indicators is conducive to improving the accuracy of donor pancreas selection and organ utilization.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), primarily manifesting as motor dysfunctions such as resting tremor, muscle rigidity, and bradykinesia. According to the classical model of basal ganglia motor control, approximately half of the medium spiny neurons (MSNs) in the striatum are D1-MSNs, which constitute the direct pathway. These neurons express D₁-dopamine receptor (D₁R) and substance P, and they mainly participate in the selection, initiation, and execution of movements. The other half are D2-MSNs, which constitute the indirect pathway. These neurons express D₂-dopamine receptor (D₂R) and adenosine 2A receptors and are involved in inhibiting unnecessary movements or terminating ongoing movements, thereby adjusting movement sequences to perform more precise motor behaviors. The direct pathway in the striatum modulates the activity of motor cortex neurons by exciting D1-MSNs through neurotransmitters such as glutamate (Glu), allowing the motor cortex to send signals more freely to the motor system, thus facilitating the generation and execution of specific motor behaviors. Studies using D1-Cre and D2-Cre mice with neurons labeled for D₁R and D₂R have shown that both types of neurons are involved in the execution of movements, with D1-MSNs participating in movement initiation and D2-MSNs in inhibiting actions unrelated to the target movement. These findings suggest that the structural and functional plasticity of D1-MSNs and D2-MSNs in the basal ganglia circuitry enables motor learning and behavioral regulation. Additionally, when SNpc DA neurons begin to degenerate, D1-MSNs are initially affected but do not immediately cause motor impairments. In contrast, when D2-MSNs undergo pathological changes, they are first activated by upstream projecting neurons, leading to the inhibition of most motor behaviors and resulting in motor dysfunction. Therefore, it is hypothesized that motor impairments such as bradykinesia and initiation difficulties are more closely related to the functional activity of D2-MSNs. The extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) signaling pathway has been identified as a critical modulator in the pathophysiology of PD. Recent findings indicate that Erk/MAPK signaling pathway can mediate DA and Glu signaling in the central nervous system, maintaining normal functional activity of striatal MSNs and influencing the transmission of motor control signals. Within this complex regulatory network, the Erk/MAPK signaling pathway plays a key role in transmitting motor information to downstream neurons, regulating normal movements, avoiding unnecessary movements, and finely tuning motor behaviors. Our laboratory’s previous research found that 4 weeks of aerobic exercise intervention improved motor dysfunction in PD mice by inhibiting the Erk1/2 signaling upstream of striatal MSNs, primarily involving the Erk1/2 signaling in D2-MSNs rather than D1-MSNs. This review summarizes the neurobiological mechanisms of Erk/MAPK signaling pathway in D2-MSNs for the prevention and treatment of motor dysfunction in PD. By exploring the role of this signaling pathway in regulating motor abnormalities and preventing motor dysfunction in the central nervous system of PD, this review provides new theoretical perspectives for related mechanistic research and therapeutic strategies.

With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

Objective To analyze the burden of disease of malignant tumors in Kunshan City from 2006 to 2021. Methods The global burden of disease research methodology was applied. The indicators of cancer incidence, mortality, and disability-adjusted life years (DALYs) in Kunshan were calculated using the data from the Tumor Registry System and Death Registry System in Kunshan. The changes in cancer were compared. Results In 2021, the number of incidences and deaths and the DALYs of cancer were 4724 cases, 1618 cases, and 20887.90 person-years, respectively. The incidence, mortality, and DALYs rates were 427.42/100000, 146.39/100000, and 18.90‰. Compared with those in 2006, the incidence rate increased by 53.40%, and the mortality and DALYs rates decreased by 24.23% and 25.73%, respectively. The DALYs rate of cancer was higher for males than for females at 22.12‰ and 15.91‰ in 2021, respectively. The DALYs rate increased with age, and it started to increase sharply after 45 years of age. The top 10 cancers in 2021 in terms of DALYs were lung cancer, stomach cancer, colorectal cancer, liver cancer, pancreatic cancer, breast cancer, leukemia, esophageal cancer, brain and nervous system cancer, and gallbladder and biliary tract cancer, accounting for 83.83% of all cancers. The proportion of years lived with disability (YLD) in DALYs increased continuously (27% in 2021), with females increasing faster than males. Conclusion The disease burden of cancer in Kunshan City remains high, and the incidence of cancer must be reduced by developing comprehensive measures and continuously strengthening the capacity of early screening and treatment of cancer.

Objective To investigate the genetic diversity of sandfly populations in endemic areas of visceral leishmaniasis in China, so as to provide references insights into management of visceral leishmaniasis and the vector sandflies. MethodsSixteen sampling sites were selected from main endemic foci of visceral leishmaniasis in China from June to September 2024, including Shanxi Province, Shaanxi Province, Henan Province, Gansu Province, Sichuan Province, and Xinjiang Uygur Autonomous Region. Sandflies were captured using light traps and manual aspirators from sheep pens, chicken coops, cave dwellings, bovinesheds, and pig pens at each sampling site. A single sandfly sample was washed in phosphate-buffered saline (PBS), and genomic DNA was extracted from sandfly samples. Cytochrome oxidase subunit 1 (COI) gene was amplified using PCR assay with universal primers, and analyzed and retrieved with the nucleotide sequence analysis tool (BLAST) software, and the sequence of COI gene was aligned with the ClustalX 1.83 and MEGA 7.0 software. The base composition and variation site of the COI gene sequence were analyzed using the software MEGA 7.0, and the number of haplotypes, total number of segregating sites, haplotype diversity, nucleotide diversity, and average nucleotide differences were calculated in the COI gene sequence using the software DnaSP 5.10, followed by Tajima’s D test for neutrality. Haplotypes were screened using the software DnaSP 5.10, and the haplotype network map of sandfly samples was plotted using the software Network 5.0. MEGA 7.0 software was employed for gene sequence editing and alignment, and calculation of genetic distances among sandfly species sampled from different regions, and a phylogenetic tree was built with a neighbor-joining method. Results A total of 466 sandflies were captured from 16 sampling sites in China from June to September 2024, and 430 gene sequences were yielded following PCR amplification and sequencing of the COI gene, with 652 to 688 bp in the length of amplification fragments. The captured sandfly samples were characterized as Phlebotomus chinensis, Sergentomyia squamirostris, Se. koloshanensis, Ph. sichuanensis, and Ph. longiductus following the COI gene sequence alignment in BLAST. A total of 251 haplotypes were identified in the 430 gene sequences from sandfly samples (50.5%), and the average haplotype diversity, nucleotide diversity and average number of nucleotide difference were 0.885, 0.257 and 160.761, respectively. The Tajima’s D values were -0.92 for sandfly populations from Yangquan City, Shanxi Province and -1.73 for sandfly populations from Sanmenxia City, Henan Province, and were all more than 0 for sandfly populations from other sampling sites. Haplotype analysis identified 50 haplotypes, which were classified into two haplogroups. Heplogroup 1 included 29 haplotypes, which had a high homology, and heplogroup 2 included 21 haplotypes. The average genetic distance was 0.000 to 0.604 among sandfly samples from different sampling sites, and phylogenetic analysis revealed that the five sandfly species were clustered into distinct clades, all with 100% clade confidence. Conclusions There is a high genetic polymorphism in the COI gene from five sandfly populations in main endemic foci of visceral leishmaniasis in China, and COI gene may serve as a marker gene for analysis of the genetic structure of sandfly populations.

Background/Aims: The association between caffeine intake and constipation remains inconclusive. This study aims to investigate whether caffeine intake is associated with constipation. Methods: This cross-sectional study included 13 941 adults from the 2005-2010 National Health and Nutrition Examination Survey. The weighted logistic regression analyses were exerted to evaluate the association between caffeine intake and constipation. Besides, stratified analyses and interaction tests were conducted to determine the potential modifying factors. Results: After adjusting for confounders, increased caffeine intake by 100 mg was not associated with constipation, as defined by stool frequency (OR, 1.01; 95% CI, 0.94-1.10) or stool consistency (OR, 1.01; 95% CI, 0.98-1.05). Subgroup analyses showed that cholesterol intake modified the relationship between increased caffeine by 100 mg and stool frequency-defined constipation (P for interaction = 0.037). Each 100 mg increase in caffeine intake was associated with a 20% decreased risk of constipation defined by stool frequency in participants who consumed high cholesterol (OR, 0.80; 95% CI, 0.64-1.00), but no association in the other 2 cholesterol level groups. Furthermore, the association between caffeine intake and stool consistency-defined constipation was not found in different cholesterol groups. Conclusions Caffeine consumption is not associated with stool frequency or consistency-defined constipation. Nevertheless, increased caffeine intake may decrease the risk of constipation (defined by stool frequency) among participants in the high-cholesterol intake group.

ObjectiveTo explore the clinical characteristics and risk factors for 30-day mortality in hospitalized patients with bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MethodsData were obtained retrospectively from the electronic medical records of inpatients at a tertiary A-grade hospital in Shanghai from January 2016 to December 2023. The collected variables included age, gender, department, surgical treatment, empirical antibiotic therapy, Pitt Bacteremia score (PBS), Charlson comorbidity index (CCI), INCREMENT-CPE score (ICS), length of hospital stay, the time from CRKP-BSI to discharge and, etc. The follow-up period ended upon discharge, with the follow-up outcomes defined as in-hospital mortality or discharge. The endpoint was defined as death within 30 days (including day 30) caused by CRKP-BSI or infection-related complications. Patients who survived within 30 days after CRKP-BSI were classified into the survival group, while those who died within 30 days were classified into the death group. Independent risk factors for 30-day mortality in patients with CRKP-BSI were analyzed using univariate and multivariate Cox regression analysis. ResultsA total of 71 hospitalized patients with CRKP-BSI, comprising 51 males and 20 females, with an average age of (65.12±18.25) years, were included during the study period. The M (P₂₅, P₇₅) of hospital stay were 37.00 (24.00, 56.00) days, and M (P₂₅, P₇₅) of the duration from CRKP-BSI to discharge or death were 18.00 (7.00, 35.00) days. There were 20 deaths (28.17%) in the death group and 51 survivors (71.83%) in the survival group. The results of multivariate Cox regression analysis showed that the ICS as an independent risk factor for 30-day mortality in CRKP-BSI patients (HR=1.379, 95%CI: 1.137‒1.671, P=0.001). Each 1-point increase in the ICS was associated with a 37.9% increase in the risk of mortality. ConclusionThe ICS is found to be a risk factor for 30-day mortality in patients with CRKP-BSI, which may facilitate the prediction for the risk of 30-day mortality and thereby support clinical decision-making for patients with CRKP-BSI.

Purpose: Diagnosing sarcopenia necessitates the measurement of skeletal muscle mass. However, guidelines lack a standardized imaging modality with thresholds validated among Asians. This systematic review compared ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and bioelectrical impedance analysis (BIA)/body composition monitoring in the detection of sarcopenia within Asian populations. Methods: PubMed and Embase were systematically searched for studies analyzing ultrasonography, CT, MRI, and BIA in diagnosing sarcopenia among Asians. Study quality was assessed using the Newcastle-Ottawa scale. Results: Pooled findings from 21,598 patients across 25 studies were examined. In receiver operating characteristic analysis, ultrasound displayed a pooled mean area under the curve (AUC) of 0.767 (95% confidence interval [CI], 0.709–0.806), with mean sensitivity of 81.1% (95% CI, 0.744–0.846) and specificity of 73.1% (95% CI, 0.648–0.774), for detecting sarcopenia in Asian populations. CT exhibited an AUC of 0.720 (sensitivity, 54.0%; specificity, 92.0%). MRI demonstrated an AUC of 0.839 (sensitivity, 67.0%; specificity, 66.0%). BIA displayed an AUC of 0.905 (95% CI, 0.842–0.968), 80.7% sensitivity (95% CI, 0.129–0.679), and 82.4% specificity (95% CI, 0.191–0.633). Conclusion Various modalities aid in diagnosing sarcopenia, and selection should be individualized. Although only BIA and dual-energy x-ray absorptiometry are recommended by the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People, ultrasound imaging may hold diagnostic value for sarcopenia in the Asian population. In certain groups, diagnostic use of CT and MRI is warranted. Future research can standardize and validate modality-specific thresholds and protocols within Asian populations.

Purpose: Diagnosing sarcopenia necessitates the measurement of skeletal muscle mass. However, guidelines lack a standardized imaging modality with thresholds validated among Asians. This systematic review compared ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and bioelectrical impedance analysis (BIA)/body composition monitoring in the detection of sarcopenia within Asian populations. Methods: PubMed and Embase were systematically searched for studies analyzing ultrasonography, CT, MRI, and BIA in diagnosing sarcopenia among Asians. Study quality was assessed using the Newcastle-Ottawa scale. Results: Pooled findings from 21,598 patients across 25 studies were examined. In receiver operating characteristic analysis, ultrasound displayed a pooled mean area under the curve (AUC) of 0.767 (95% confidence interval [CI], 0.709–0.806), with mean sensitivity of 81.1% (95% CI, 0.744–0.846) and specificity of 73.1% (95% CI, 0.648–0.774), for detecting sarcopenia in Asian populations. CT exhibited an AUC of 0.720 (sensitivity, 54.0%; specificity, 92.0%). MRI demonstrated an AUC of 0.839 (sensitivity, 67.0%; specificity, 66.0%). BIA displayed an AUC of 0.905 (95% CI, 0.842–0.968), 80.7% sensitivity (95% CI, 0.129–0.679), and 82.4% specificity (95% CI, 0.191–0.633). Conclusion Various modalities aid in diagnosing sarcopenia, and selection should be individualized. Although only BIA and dual-energy x-ray absorptiometry are recommended by the Asian Working Group for Sarcopenia and the European Working Group on Sarcopenia in Older People, ultrasound imaging may hold diagnostic value for sarcopenia in the Asian population. In certain groups, diagnostic use of CT and MRI is warranted. Future research can standardize and validate modality-specific thresholds and protocols within Asian populations.