To systematically analyzed the reporting status of core elements in publicly available clinical practice guideline(hereafter referred to as "guideline") protocols published domestically and internationally over the past decade, identified existing problems, and provided evidence to inform the standardized writing and publication of future guideline protocols.

OBJECTIVE To analyze the characteristics and influencing factors of disposal behavior of expired medicines among Chinese residents across regional divisions， and to provide references for regional classification management and precise policy implementation regarding expired medicines. METHODS A stratified random sampling method was employed to conduct a questionnaire survey among residents across sample provinces and cities， utilizing a combination of online and offline approaches. Binary Logistic regression analysis was used to systematically explore the regional （eastern， central and western regions） and urban-rural disparities in the recycling of expired medicines among Chinese residents， identify the core driving factors influencing standardized disposal behaviors， and propose corresponding recommendations. RESULTS A total of 2 200 ques tionnaires were collected， with 2 159 deemed valid， yielding an effective response rate of 98.1%. The surveyed residents commonly stored medicines at home （67.7%）， yet the rate of regular medicine clearance was low （only 57.7%）. Nearly half of the residents （49.7%） had expired medicines in their households， with improper disposal of expired medicines remaining the predominant behavior. Insufficient convenience in recycling was identified as the primary reason for improper disposal of expired medicines （50.1%）. Statistically significant differences were observed between residents in the eastern， central and western regions， as well as between urban and rural residents， in terms of household medicine storage rates and the prevalence of expired medicine possession （ P ＜0.05）. However， no statistically significant difference was found in the standardized disposal rates across regional divisions （ P ＞0.05）. Furthermore， the residents demonstrated a higher level of awareness regarding the health hazards of expired medicines compared to their awareness of environmental hazards， with 46.0% and 32.1% indicating they were “relatively familiar” and “very familiar”， respectively. The participation rate in standardized recycling was only 37.6%. Among non-participating residents， the three primary barriers were “recycling points being too far away” （46.6%）， “unawareness of recycling channels” （46.1%） and “lack of incentives” （48.1%）. The surveyed residents showed relatively high trust in pharmaceutical regulatory authorities and on-site recycling personnel， with “high trust” accounting for 31.2% and 34.7%， respectively. Binary Logistic regression analysis results indicated that the awareness of environmental hazards and the accessibility of recycling points were the core driving factors for proper disposal. CONCLUSIONS Significant issues exist in the recycling of expired medicines among Chinese residents， characterized by “improper behavior， cognitive bias， and unbalanced system”. It is recommended to construct a tiered recycling network focusing on “quality improvement in the eastern region， expansion in the central region， and basic coverage in the western region”， implement targeted educational campaigns and differentiated incentive policies. Moreover， the specific needs of groups such as the elderly should be addressed to achieve spatial equalization and service optimization of the recycling system.

OBJECTIVE To evaluate the cost-effectiveness of cefiderocol versus best available therapy （BAT） or standard-of- care （SOC） for the treatment of confirmed or suspected carbapenem-resistant Gram-negative bacterial （CRGNB） serious infections from the perspective of the Chinese healthcare system， and to explore its reasonable pricing. METHODS A decision tree model was constructed based on data from two phase Ⅲ clinical trials （CREDIBLE-CR and GAME CHANGER） to simulate the cost- effectiveness of cefiderocol in two scenarios： salvage therapy for confirmed CRGNB infection （scenario 1） and empirical therapy for suspected CRGNB infection （scenario 2）. The primary outcome measure was the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） was set at 1 to 3 times China’s per capita GDP in 2024. To verify the robustness of the results， one- way and probabilistic sensitivity analyses were conducted， and based on these， a reasonable price range for cefiderocol in the Chinese market was explored. RESULTS The results for scenario 1 showed that the clinical cure rate in the cefiderocol group was higher than that in the BAT group （47.50% vs. 34.21%）， but its ICER was 415 065.03 yuan per cured case， exceeding three times China’s GDP per capita. Scenario 2 revealed that the ICER for cefiderocol relative to SOC was as high as 1 362 446.16 yuan per cured case， far exceeding the WTP. Sensitivity analysis indicated that the treatment duration and price of cefiderocol were key factors affecting its cost-effectiveness. In the two scenarios described above， the unit price of cefiderocol must fall below 683.47 and 242.00 yuan/g， respectively， to be considered cost-effective. CONCLUSIONS Based on the current market price， cefiderocol lacks sufficient cost-effectiveness for treating confirmed or suspected CRGNB serious infections within China’s healthcare system. To improve its accessibility， price negotiations or a tiered medical insurance payment strategy are required.

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 Gestational weight gain is closely related to maternal and infant health outcomes. Pregnant women are simultaneously exposed to four metals—lithium (Li), vanadium (V), uranium (U), and bismuth (Bi)—through inhalation of fine particulate matter and consumption of contaminated food and water. Existing studies suggest that exposure to these metals may be associated with gestational weight gain. However, no study has yet explored the complex relationships between exposure to mixtures of these four metals and weight gain at different stages of pregnancy. Objective To investigate the associations between mixed exposure to Li, V, U, and Bi in early pregnancy and the average weekly gestational weight gain during both early pregnancy and mid-to-late pregnancy. Methods This prospective study recruited eligible women in early pregnancy from an obstetrics clinic of a tertiary hospital in Jinan, China, between September 2021 and July 2023. Pre-pregnancy weight, current weight (at 11⁺⁰ to 13⁺⁶ weeks of gestation), and spot urine samples (≥5.0 mL) were collected at enrollment. Urinary concentrations of Li, V, Bi, and U were determined using inductively coupled plasma mass spectrometry. Participants were followed up in late pregnancy (≥28 weeks of gestation) to collect information on physical activity via questionnaire; weight measurements at the last antenatal visit (35⁺⁰ to 37⁺⁶ weeks of gestation) were obtained from the hospital information system. After adjusting for covariates, multiple linear regression and generalized additive models were used to assess the associations of individual metals with weekly weight gain in early pregnancy and in mid-to-late pregnancy. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (Qgcomp) were applied to evaluate the joint effects of the metal mixture exposure on weekly weight gain at the two gestational stages. Results A total of 313 pregnant women were included. The geometric means of urinary Li, V, U, and Bi concentrations were 37.07, 0.20, 0.06, and 0.04 μg·L⁻¹, respectively; after creatinine adjustment, the corresponding values were 46.82, 0.25, 0.07, and 0.05 μg·g⁻¹ (Cr). The mean weekly gestational weight gain was (0.19±0.25) kg in early pregnancy and (0.53 ± 0.18) kg in mid-to-late pregnancy. Both multiple linear regression and generalized additive models showed that urinary V concentration was positively associated with average weekly gestational weight gain in early pregnancy, while no significant associations were found for other metals or for gestational weight gain in mid-to-late pregnancy. In the BKMR model with early-pregnancy weight gain as the outcome, V had the strongest association [posterior inclusion probability (PIP)=0.773]. When other metals were fixed at their medians, V showed a positive non-linear association with the outcome. A significant single-metal effect of V and its interaction with Li were observed. Compared with the 50th percentile of the metal mixture, the average weekly weight gain in early pregnancy increased by 0.016 (95%CI: 0.003, 0.029) and 0.018 (95%CI: 0.001, 0.036) at the 60th and 65th percentiles, respectively; conversely, at the 25th percentile, it decreased by 0.026 (95%CI: 0.002, 0.050). Overall, the joint effect of the metal mixture on early- pregnancy weight gain showed an upward trend. In the BKMR model for mid-to-late pregnancy gestational weight gain, all PIPs were<0.5, and no significant single-metal effects, interactions, or joint effects were identified. Qgcomp results confirmed a positive association between the metal mixture and early-pregnancy weight gain (b=0.031, 95%CI: 0.010, 0.051; P<0.01), with V contributing the highest positive weight (0.71). No significant association was found for weight gain in mid-to-late pregnancy (b=0.007, P=0.339). Conclusion Higher levels of co-exposure to the Li, V, Bi, and U metal mixture during early pregnancy may be associated with increased average weekly weight gain in early pregnancy. Among these metals, V exhibits a predominant role and appears to interact with Li. No association is observed between early-pregnancy metal mixture exposure and average weekly gestational weight gain in mid-to-late pregnancy. These findings suggest that monitoring and managing metal exposure during early pregnancy may be crucial for the rational regulation of gestational weight gain.

OBJECTIVE: To explore the methods, fixation points, and effectiveness of staged therapy using external fixation frame in treatment of infectious nonunion near knee joint. METHODS: A retrospective analysis was conducted on the clinical data of 60 patients with infectious nonunion near knee joint, who underwent staged therapy using external fixation frame between June 2021 and June 2024 and were followed up. There were 48 males and 12 females with an average age of 47.9 years (range, 16-70 years). The disease duration ranged from 9 months to 20 years, with a median of 14 months. Among them, 21 cases of infectious nonunion located in the distal femur, 36 cases in the proximal tibia, and 3 cases in the patella; 12 cases exhibited segmental bone defects (≥4 cm), while 48 cases presented with localized bone defects (<4 cm). Osteomyelitis was classified using the Cierny-Mader system, with 3 cases classified as type Ⅰ, 6 cases as type Ⅱ, 35 cases as type Ⅲ, and 16 cases as type Ⅳ. Preoperative C-reactive protein levels ranged from 15.1 to 55.8 mg/L (mean, 36.4 mg/L). The erythrocyte sedimentation rate was 35-80 mm/1 h (mean, 56.9 mm/1 h). The Hospital for Special Surgery (HSS) score for knee joint was 69.3±17.7 and the range of motion was (70.61±40.60)°. After debridement and placement of antibiotic carriers at the first-stage operation, unilateral orbital frames ( n=14), combined frames ( n=27), or Ilizarov frames ( n=19) were used for cross joint fixation ( n=9) or joint preservation fixation ( n=51). After 6-8 weeks of infection control, the bone grafting or bone transport was performed at the second-stage operation based on the type of bone defect, with internal fixation employed as an adjunct if necessary. After operation, the infection control and fracture healing were observed and the bone healing time was recorded. The knee joint function was assessed using the HSS score, and the knee joint range of motion was measured as well as the angle of motion loss. Patients were grouped according to the site of nonunion, type of external fixation frame, and fixation method. The bone healing time, change value of HSS score, and knee joint range of motion loss (difference between pre- and post-operation) were compared between groups. RESULTS: All infection markers returned to the normal range within 6 weeks after the first-stage operation. All patients were followed up 12-48 months (mean, 22.0 months) after the second-stage operation. There were 5 cases of needle tract infection during the external fixation period, and 3 cases of infection recurrence after the second-stage operation, all of which were cured after symptomatic treatment. The bone healing time was 6-18 months (mean, 11.0 months). At last follow-up, the HSS score was 88.5±7.9 and the range of motion was (61.84±40.59)°, with significant differences compared to preoperative values ( P<0.05); the knee joint range of motion loss was (8.77±11.07)°. The bone healing time was significantly longer in the distal femur group than in the proximal tibia group ( P<0.05), and in the unilateral orbital frames group than in the Ilizarov frames group and the combined frames group ( P<0.05). The angle of motion loss was significantly larger in the Ilizarov frames group than in the unilateral orbital frames group and the combined frames group ( P<0.05). The change value of HSS score was significantly higher in the cross joint fixation group than in the joint preservation fixation group ( P<0.05). CONCLUSION During the first-stage operation, debridement is performed and antibiotic carriers are placed to control infection. External fixation frames are then precisely positioned based on the distance between the lesion and the joint surface, avoiding the infected wound while ensuring mechanical balance. During the second-stage operation, bone grafting options are selected according to the extent of bone defects to enhance the bone union. Postoperative early functional exercises of the knee joint are permitted to improve joint function.
Humans ; Male ; Female ; Middle Aged ; Adult ; Fractures, Ununited/surgery* ; Retrospective Studies ; External Fixators ; Aged ; Knee Joint/surgery* ; Adolescent ; Young Adult ; Treatment Outcome ; Osteomyelitis/surgery* ; Fracture Fixation/instrumentation* ; Bone Transplantation ; Tibial Fractures/surgery*

Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

BACKGROUND: Lung cancer has the highest mortality rate among all malignant tumors, and non-small cell lung cancer (NSCLC) accounts for about 80%-85% of all lung cancers. Lobectomy and lymph node dissection are one of the most important treatment methods, and lymph node dissection, as an important part, has attracted much attention. And its mode and scope of dissection may affect postoperative complications, particularly the occurrence of chronic cough. The aim of this study is to investigate the effect of lymph node dissection on postoperative chronic cough in patients with NSCLC undergoing lobectomy, and to provide clinical evidence for optimizing surgical strategy and reducing postoperative chronic cough. METHODS: A retrospective analysis was conducted on the clinical data of 365 NSCLC patients who underwent lobectomy at the First Affiliated Hospital of University of Science and Technology of China from December 2020 to December 2023. The relationship between clinical characteristics and postoperative chronic cough was analyzed. The Chinese version of the Leicester Cough Questionnaire (LCQ-MC) scores were collected from the patients at 2 time points: 1 day before surgery and 8 weeks after surgery. Patients were divided according to lymph node dissection methods, to explore the relationship between lymph node dissection and chronic cough after lobectomy. Additionally, patients were divided into chronic cough and non-chronic cough groups based on the presence of postoperative chronic cough, to investigate whether perioperative data, lymph node dissection methods, and lymph node dissection regions were influencing factors. RESULTS: Patients undergoing lobectomy were more likely to have chronic cough after surgery in the systematic lymph node dissection group than in the lymph node sampling group (P<0.05). LCQ-MC scale evaluation showed that the psychological, physiological, social and total score of the patients in systematic lymph node dissection group were significantly lower than those in lymph node sampling group (P<0.05). Multivariate analysis showed that anesthesia time, operation site, lymph node dissection method, whether to perform upper mediastinal lymph node dissection, number of upper mediastinal lymph node dissection, whether to perform lower mediastinal lymph node dissection and total number of lymph node dissection were independent risk factors for postoperative chronic cough in NSCLC patients (P<0.05). CONCLUSIONS When NSCLC patients underwent lobectomy, lymph node sampling was associated with a significantly lower risk of chronic cough than systematic lymph node dissection. Dissecting lymph nodes in the upper and lower mediastinal regions and the number of lymph nodes dissected may increase the risk of postoperative cough and reduce the quality of life of patients after surgery.
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Male ; Female ; Lung Neoplasms/surgery* ; Middle Aged ; Cough/etiology* ; Retrospective Studies ; Lymph Node Excision/methods* ; Aged ; Chronic Disease ; Postoperative Complications/etiology* ; Adult ; Lymph Nodes/surgery* ; Pneumonectomy/adverse effects* ; Chronic Cough

Objective:To summarize and analyze the clinical characteristics of patients with sudden sensorineural hearing loss（SSHL） accompanying diabetes mellitus, to explore whether diabetes affects the treatment outcomes during hospitalization, and to identify the factors influencing the efficacy of SSHL patients with diabetes. Methods:A retrospective analysis was conducted on clinical data from 939 patients with SSHL. The baseline characteristics, and onset conditions of the diabetes group（79 cases） and the non-diabetes group（860 cases） were compared. Propensity score matching（PSM） was applied in a 1︰ 2 ratio to match initial hearing levels with baseline characteristics such as age, sex, and BMI, resulting in 73 diabetes cases and 144 non-diabetes cases for treatment efficacy comparison. For the analysis of prognostic factors, a logistic regression model was established based on the treatment outcomes of 217 patients with SSHL. Results:The proportion of SSHL patients accompanying diabetes was 8.40%（79/939）. Compared to non-diabetic patients, those with diabetes were older（median age of 53 years in the diabetes group and 39 years in the non-diabetes group） and had a higher proportion of hypertension（43.04% vs 12.67%）, with significant difference observed（P<0.05）. After PSM, the treatment efficacy during hospitalization was better in the diabetes group than in the non-diabetes group（58.90% vs 47.92%）, although the difference was not statistically significant（P>0.05）. The prognosis of patients with SSNHL accompanied by diabetes was analyzed using a multivariate logistic regression model that included age, HDL-C, and INR as variables; however, no statistically significant differences were found（P>0.05）. Conclusion:Patients with SSHL accompanying diabetes are generally older with a higher incidence of hypertension. The presence of diabetes does not affect the treatment outcomes during hospitalization.
Humans ; Propensity Score ; Retrospective Studies ; Hearing Loss, Sensorineural/therapy* ; Hearing Loss, Sudden/therapy* ; Middle Aged ; Diabetes Mellitus ; Male ; Female ; Prognosis ; Adult ; Logistic Models ; Diabetes Complications ; Aged ; Treatment Outcome

Objective:To investigate the application value of intraoperative electrocochleography（ECochG） monitoring technique and insertion techniques in cochlear implant（CI） and analyze its relationship with postoperative residual hearing（RH） preservation. Methods:Thirty-one patients（35 ears） who received CI in our hospital from June 2022 to July 2024 were enrolled. The Advanced Bionics Active Insertion Monitoring（AIM） system was used for real-time ECochG monitoring during surgery. Intraoperative cochlear microphonics （CM） waveform changes were recorded and analyzed in relation to postoperative RH preservation. Results:①ECochG recordings were successfully obtained in 34 of 35 ears （97.1%）. ②According to Harris classification, there were 7 ears（20.6%） of Type A（rising）, 7 ears（20.6%） of Type C（declining）, 8 ears（23.5%） of Type CC（fluctuating）, and 12 ears（35.3%） of Type D（no response）. ③The total CM amplitude decrease was significantly moderately correlated with postoperative low-mid frequency hearing loss（r=0.67, P=0.017）. The total CM amplitude decrease was significantly moderately correlated with postoperative low frequency hearing loss（r=0.65, P=0.023）. ④For the mean amplitude variation, the Amax was 30.70 μV, the Amin was 8.64 μV, and the Aend was 18.27 μV. ⑤Sixteen cases completed postoperative follow-up, with an average low-mid frequency（125-1 000 Hz） residual hearing loss of 15.25 dB HL and a RH preservation rate of 87.5%. Conclusion:Intraoperative ECochG monitoring can effectively predict postoperative residual hearing changes, effectively guide surgical manipulation, and improve residual hearing preservation rate.
Humans ; Cochlear Implantation/methods* ; Audiometry, Evoked Response ; Cochlear Implants ; Male ; Female ; Adult ; Middle Aged ; Monitoring, Intraoperative ; Adolescent ; Young Adult ; Minimally Invasive Surgical Procedures ; Child ; Aged ; Postoperative Period