[The efficacy and safety of immunotherapy combined with chemotherapy neoadjuvant in locally advanced resectable hypopharyngeal squamous cell carcinoma].

Objective: To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients. Methods: This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy. Results: By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence. Conclusions: The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

[Overview of the ten global conferences on health promotion and implications for future work].

Since 1986, the WHO has held ten global health promotion conferences covering various health promotion issues and sustainable development worldwide. These sessions have formed a series of consensus and actions that guide promoting health globally. This study analyzed the declarations, reports, and news materials from the ten conferences that studied health promotion action areas, focal topics, actor networks, partnership relationships, and other significant outcomes. It also explored how these conferences contributed to the construction and advancement of global health promotion consensus and actions. The first Global Conference on Health Promotion identified the concept of health promotion and five key action areas, laying the foundation for subsequent conferences and health promotion actions. Over the years, the ten conferences continuously expanded the essence of health promotion, developed partnership relationships, formulated public health promotion policies, and called for health promotion actions. This process culminated in the formation of global consensus and collective actions. The latter conferences have gained significant attention and influence. The conferences offer valuable insights for future global health promotion endeavors and provide global perspectives and pathways for the development of Healthy China.

[Analysis of risk factors of short-term prognosis in patients with severe Budd-Chiari syndrome].

Objective: To explore the risk factors of short-term prognosis of severe BCS patients,established and verified the nomogram prediction model for these BCS patients and evaluated its clinical application value. Methods: This study is a retrospective cohort study. The clinical data of 171 patients with severe BCS diagnosed were retrospectively analyzed in the Department of Hepatopancreatobiliary Surgery First Affiliated Hospital of Zhengzhou University from January 2018 to December 2023. There were 105 males and 66 females, aged (52.1±12.8) years (range: 18 to 79 years). The patients were divided into two groups based on whether they died within 28 days: the death group (n=38) and the survival group (n=133). The risk factors for short-term death of patients were analyzed,and independent risk factors were screened by univariate and multivariate analysis. Furthermore,these factors were used to establish the nomogram prediction model. The area under the curve(AUC),the Bootstrap Resampling,the Hosmer-Lemeshow test and the Decision Curve Analysis(DCA) were used to verify the model's differentiation,internal verification,calibration degree and clinical effectiveness,respectively. Results: Univariate and multivariate Logistics regression analysis showed that the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time are independent risk factors (P<0.05). The above factors were used to successfully establish the prediction model with 0.908 of AUC and 0.895 of the internal verification of AUC,indicating that the predictive model was valuable. The 0.663 P-values in the Hosmer-Lemeshow test indicated the high calibration degree of the model. The clinical effectiveness of the model was proved by the 18% clinical benefit population using the DCA curve with the 17% probability threshold. Conclusions: The independent risk factors are the history of hepatic encephalopathy,white blood cell,glomerular filtration rate and prothrombin time. An adequate basis was acquired by establishing a nomogram prediction model of the short-term prognosis of severe BCS,which was helpful for early clinical screening and identification of high-risk patients with severe BCS who could die in the short term and timely providing timely intervention measures for improving the prognosis.

TFP5, a Peptide Derived from Cdk5 Activator p35, Protects Pancreatic ß Cells from Glucose Toxicity.

We studied the effect of TFP5 on MIN6 cells (cultured mouse islet ß cells) treated with different concentrations of glucose (5 or 25 mM). The results were verified in C57BL/6J mice (control; n=12) and db/db mice with type 2 diabetes mellitus (n=12). To synthesize TFP5, peptide p5 (a derivative of p35 protein, activator of cyclin-dependent kinase 5, Cdk5) was conjugated with a FITC tag at the N-terminus and an 11-amino acid TAT protein transduction domain at the C-terminus. TFP5 was employed to inhibit Cdk5 activity and then to evaluate its efficiency in treating experimental type 2 diabetes mellitus. TFP5 effectively inhibited the pathological hyperactivity of Cdk5, enhanced insulin secretion, and protected pancreatic ß cells from apoptosis in vitro and in vivo. In addition, TFP5 inhibited inflammation in pancreatic islets by reducing the expression of inflammatory cytokines TGF-ß1, TNFα, and IL-1ß. These novel data indicates that TFP5 is a promising candidate for treatment of type 2 diabetes mellitus.

[Predictor of clinical response to subcutaneous immunotherapy with dust mites in polysensitized allergic rhinitis patients].

Objective: To evaluate the efficacy of 1-year subcutaneous immunotherapy (SCIT) with dust mites in polysensitized allergic rhinitis (AR) patients and to analyze the serological markers associated with clinical response. Methods: A retrospective analysis of data from 69 polysensitized AR patients who completed 1-year SCIT with dust mites from Oct 2020 to Mar 2022 in Shandong Provincial ENT Hospital was conducted. The median patient age was 21 years, including 41 males and 28 females. The changes in symptoms and serum IgE, IgG4 assessed before and after treatment were evaluated. The differences in serological markers between effective and ineffective groups were analyzed. Multivariate regression analysis was used to investigate the predictors of clinical response. SPSS 22.0 software was used for data processing. Results: After immunotherapy, there was a significant reduction in symptom scores and a substantial improvement in the quality of life of polysensitized AR patients (all P<0.001). Dust mite specific IgG4 (sIgG4) significantly increased and dust mite specific IgE (sIgE)/sIgG4 significantly decreased (all P<0.05). sIgE, total IgE (tIgE), sIgE/tIgE and sIgE/sIgG4 were significantly lower in ineffective group than those in effective group (all P<0.05). The clinical response of SCIT related only to dust mite sIgE (r=0.29, P=0.036), and sIgE≥53.86 kU/L had the best sensitivity (77.78%) and specificity (57.89%) to predict effective SCIT in polysensitized AR patients. Conclusions: One-year dust mite SCIT is effective for polysensitized AR patients. Pre-treatment serum dust mite sIgE≥53.86 kU/L may play a role in predicting clinical response of dust mite SCIT in polysensitized AR patients.

[Screening and validation of pivotal genes in hepatitis B virus-associated hepatocellular carcinoma].

Objective: To screen the pivotal genes involved in the occurrence and development of HBV-associated HCC. Additionally, perform validation and biological function analysis to evaluate changes in the expression of pivotal genes and their prognostic value in patients with hepatocellular carcinoma. Methods: The GSE121248 gene expression profile data of HBV-HCC patients were searched and downloaded from the GEO database. The R language was used to compare the differences in gene expression between hepatocellular carcinoma and paracancerous tissues. KEGG and GO function enrichment analyses were performed on the differential genes. PPI plots and pivotal gene screening were carried out through online tools like STRING and Cytoscape software. 369 cases of hepatocellular carcinoma and 160 healthy controls in TCGA and GTEx were used as validation cohorts to verify the expression levels of the pivotal genes. A Kaplan-Meier plot was drawn to evaluate the prognostic value of the pivotal gene. Results: A total of 120 differentially expressed genes were screened, of which 89 were up-regulated and 31 were down-regulated. Differential genes were mainly enriched in the metabolic pathways related to retinol metabolism, cytochrome P450 metabolism, and the p53 signaling pathway. The top 10 differential genes were selected as pivotal genes by the Cytoscape plug-in cytoHubba. There were significant differences in the expression levels of four types of CCNB1, CDK1, RRM2, and TOP2A genes in the validation cohort. All four types of genes were up-regulated. Survival analysis showed that patients with elevated expression levels of four genes had a poorer prognosis, with statistical differences in results. Conclusion: Four types of genes, CCNB1, CDK1, RRM2, and TOP2A, have high expression levels in patients with HBV-HCC and are correlated to shorter survival times, making them a potential target for diagnosis, prognosis, and treatment.

[A case report of ocular monkeypox].

A 35-year-old male patient arrived at the clinic, reporting a persistent issue of his right eye being difficult to open for the past three weeks. Alongside this, he had been experiencing a gradual development of lesions around the eye. Notably, about a month prior to the onset of these symptoms, the patient had engaged in unprotected intercourse with a male partner. The initial manifestation was a papule near the eye, which then rapidly progressed. Laboratory analysis of samples taken from the lesions confirmed the presence of monkeypox through polymerase chain reaction testing. Furthermore, this patient received positive diagnoses for both HIV and syphilis infections. Notably, his absolute CD4 count was measured at an extremely low level of 2 cells/µl.(This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on September 18, 2023).

[Development and validation of prognostic nomogram for malignant pleural mesothelioma].

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.

[Comparative study of medical common data models for FAIR data sharing].

The common data model (CDM) is an important tool to facilitate the standardized integration of multi-source heterogeneous healthcare big data, enhance the consistency of data semantic understanding, and promote multi-party collaborative analysis. The data collections standardized by CDM can provide powerful support for observational studies, such as large-scale population cohort study. This paper provides an in-depth comparative analysis of the data storage structure, term mapping pattern, and auxiliary tools development of the three international typical CDMs, then analyzes the advantages and limitations of each CDM and summarizes the challenges and opportunities faced in the CDM application in China. It is expected that exploring the advanced technical concepts and practical patterns of foreign countries in data management and sharing will provide references for promoting FAIR (findable, accessible, interoperable, reusable) construction of healthcare big data in China and solving the current practical problems, such as the poor quality of data resources, the low degree of semantization, and the inabilities of data sharing and reuse.

[A new understanding of wound repair after surgery for benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men. Transurethral resection of prostate (TURP), as an important BPH treatment, is also the most effective way to relieve prostatic obstruction. However, postoperative complications, such as lower urinary tract symptoms (LUTS), infection, hematuria and bladder neck contracture, may still occur, which seriously impact the therapeutic effect and patients' quality of life. The wound healing after BPH surgery is closely associated with the occurrence of postoperative complications. Therefore, comprehensively understanding the influencing factors of wound healing and designing tailored interventions will be particularly important for reducing postoperative complications of BPH.

Voting restrictions associated with health inequities in teenage birth rates.

OBJECTIVES: Since the Landmark Shelby V. Holder Supreme Court Ruling, the number of laws in the United States that make it difficult to vote has increased dramatically. This may lead to legislation that limits access to health care, including options for family planning services. We determine whether voting restrictions are associated with county-level teenage birth rates. STUDY DESIGN: This is an ecological study. METHODS: The Cost of Voting Index, a state-level measure of barriers to voting during US elections from 1996 to 2016, was used as a proxy for access to voting. County-level teenage birth rates were obtained from the County Health Rankings data. We used multilevel modeling to determine whether restrictive voting laws were associated with county-level teenage birth rates. We tested whether associations varied across racial and socio-economic groups. RESULTS: When confounders were included, a significant association was observed between increasing voting restrictions and teenage birth rates (ß = 1.72, 95% confidence interval: 0.54, 2.89). A Cost of Voting Index-median income interaction term was tested and was statistically significant (ß = -1.00, 95% confidence interval: -1.36, -0.64), indicating that the observed relationship was particularly strong among lower-income counties. The number of reproductive health clinics per capita within each state is a potential mediator. CONCLUSION: Restrictive voting laws were associated with higher teenage birth rates, particularly for low-income counties. Future work should use methods in which a causal relation can be identified.

[Yin Chan Quan Shu, the Obstetrics and Gynecology Monograph by Wang Kentang].

Yin Chan Quan Shu (Obstetrics and gynecology monograph) is a monograph on obstetrics and gynecology compiled by Wang Kentang in the Ming Dynasty. It had four volumes and was published in the thirtieth year of Wanli (1602) in the Ming Dynasty after it was edited by Zhang Shoukong and others. It was found that Yin Chan Quan Shu has four versions remaining. They were the version printed by Shu Lin Qiao Shan Tang in the Ming Dynasty, held in the National Library of China and the Cabinet Library of Japanese Official Documents Library; the version revised according to the version of Shu Lin Qiao Shan Tang, held in the Library of Capital Medical University, Tianjin Medical College, Shanghai Branch of the Chinese Medical Association, the Library of Guangzhou University of Chinese Medicine and the Cabinet Library of the National Archives of Japan; the version based on the version of Shu Lin Qiao Shan Tang in the Ming Dynasty, transcribed in the fourth year of Wen Hua (1807), collected in the Cabinet Library of the National Archives of Japan; the version transcribed according to the revised version in the Ming Dynasty, collected in the Shanghai Branch of the Chinese Medical Association. It was found that there was no evidence to support the existence of the so-called "version of Kangxi in the Qing Dynasty". This means almost all versions remaining came from the versions published in the Ming Dynasty. The references of Yin Chan Quan Shu came from Pulse Classic (Mai Jing), Chan Bao, Fu Ren Da Quan Liang Fang and other works with the supplement and development by Wang Kentang.Yin Chan Quan Shu was the main sources and foundation of the Criteria of Syndrome Identification and Treatment in Gynecology (Nv Ke Zheng Zhi Zhun Sheng) by Wang Kentang.

[Three-dimensional analysis of maxillary dentition during molar distalization with clear aligners under different movement designs: an in vitro experiment].

Objective: To investigate the three-dimensional force in the maxillary dentition under different movement designs for molar distalization with clear aligners Methods: Three groups were designed: simultaneous movement group (simultaneous distalization of maxillary first and second molars), second molar movement group (distalization of maxillary second molars) and first molar movement group (distalization of maxillary first molars). Ten clear aligners were made in each group, and the displacement was designed to be 0.2 mm. A force sensing device was established to measure the three-dimensional force on the upper dentition with the clear aligner. The device contained a model of the maxillary dentition consisting of 14 teeth, each tooth connected to an individual sensor. After the clear aligner was fitted, the data of 14 sensors were collected and analyzed using computer analysis software. The moving teeth were taken as the target teeth, and the rest of the teeth were anchorage. The data of the three-dimensional force in the three groups in each tooth position were measured and compared. Results: The sagittal forces on the first and second molars in the simultaneous movement group were (5.61±0.94) and (5.81±1.08) N, respectively, which were significantly smaller than those of the target teeth in the same position in other groups (P<0.05). The second molars in the first molar movement group received a sagittal reaction force, which was (-6.73±1.99) N. The anterior teeth in the three groups were all subjected to sagittal reaction force, and the force value was in a range of (-3.33 to 0.46) N. In the coronal direction, the second premolars of the simultaneous movement group received the reaction force in the palatal direction, and the force value was (-2.17±1.06) N. The first molars in the second molar movement group were also subjected to palatal reaction force of (-1.99±0.70) N. The second molars and second premolars in the first molar movement group were also subjected to palatal reaction force, which were (-2.85±0.57) and (-1.85±0.74) N, respectively. Compared with the sagittal and coronal forces, the target teeth and anchorage teeth in the three groups were less stressed in the vertical direction. Conclusions: The first and second molars distalized simultaneously, the correction force in the sagittal direction was relatively small. When first molar was moved distally alone, a greater reaction force in the sagittal direction was exerted on the second molar. Buccal displacement of the adjacent anchorage teeth should be designed to counteract the palatal reaction force on the anchorage teeth as the molars moved distally.

[Recommendations of diagnosis and treatment of giant cell arteritis and polymyalgia rheumatic in China].

Polymyalgia rheumatica (PMR) is a syndrome characterized by pain and morning stiffness in the neck and shoulder and pelvic girdles, as well as raised acute-phase reactants, with or without systemic symptoms, such as fever. Giant cell arteritis (GCA) is a systemic vasculitis of unclear etiology that involves systemic arteries, principally affecting medium- and large-sized arteries with skipped, segmental alterations and granulomatous vasculitis seen on histopathology. In China, epidemiological data describing GCA are still limited; thus, the prevalence might be underestimated. The involvement of vessels in GCA can cause irreversible visual impairment or loss and stroke, which are serious complications. PMR is three times more prevalent than GCA, and other specific diseases should be excluded before the diagnosis is established. PMR symptoms can be present in 40%-60% of patients with GCA. Conversely, GCA can develop in 15% of patients with PMR. Chinese Rheumatology Association, based on the clinical diagnosis and treatment guidelines in 2005, utilizing the experience and guidelines of diagnosis and treatment at home and abroad, formulated this specification to standardize the diagnosis and treatment of GCA and PMR and improve the patient's prognosis.

[Clinicopathological analysis of superior mediastinal lymph node metastases in medullary thyroid carcinoma].

Objective: To investigate the clinicopathological characteristics of superior mediastinal lymph node metastases (sMLNM) in medullary thyroid carcinoma (MTC). Methods: This retrospective analysis enrolled the patients who were treated for sMLNM of MTC in our hospital from May 2012 to January 2021. All patients were suspected of sMLNM due to preoperative imaging. According to the pathological results, the patients were divided into two groups named sMLNM group and the negative superior-mediastinal-lymph-node group. We collected and analyzed the clinical features, pathological features, pre- and post-operative calcitonin (Ctn), and carcinoembryonic antigen (CEA) levels of the two groups. Logistic regression analysis was used to analyze risk factors, and receiver operation characteristic (ROC) curves were drawn to determine the optimal cut-off values of preoperative Ctn and preoperative CEA for predicting sMLNM. Results: Among the 94 patients, 69 cases were in the sMLNM group and 25 cases were in the non-SMLNM group. Preoperative Ctn level (P=0.003), preoperative CEA level (P=0.010), distant metastasis (P=0.022), extracapsular lymph node invasion (P=0.013), the number of central lymph node metastases (P=0.002) were related to sMLNM, but the multivariate analysis did not find any independent risk factors. The optimal threshold for predicting sMLNM by pre-operative Ctn is 1500 pg/ml and AUC is 0.759 (95% CI: 0.646, 0.872). The sensitivity, specificity, positive predictive value, and negative predictive value of diagnosis are 61.2%, 77.3%, 89.1%, 39.5%, respectively. In patients who underwent mediastinal lymph node dissection through transsternal approach, the metastatic possibility of different levels from high to low were level 2R (82.3%, 28/34), level 2L (58.8%, 20/34), level 4R (58.8%, 20/34), level 3 (23.5%, 8/34), level 4L (11.8%, 4/34). Postoperative complications occurred in 41 cases (43.6%), and there was no perioperative death in all cases. 14.8% (12/81) of the patients achieved biochemical complete response (Ctn≤12 pg/ml) one month after surgery, 5 of these patients were in sMLNM group. Conclusions: For patients who have highly suspicious sMLNM through imaging, combining with preoperative Ctn diagnosis can improve the accuracy of diagnosis, especially for patients with preoperative Ctn over 1 500 pg/ml. The superior mediastinal lymph node dissection for the primary sternotomy should include at least the superior mediastinal levels 2-4 to avoid residual lesions. The strategy of surgery needs to be cautiously performed. Although the probability of biochemical cure in sMLNM cases is low, nearly 40% of patients can still benefit from the operation at the biochemical level.

Microarray profiling identifies hsa_circ_0082003 as a novel tumor promoter for papillary thyroid carcinoma.

BACKGROUND: Circular RNAs (circRNAs) are non-coding RNAs that have essential regulatory roles in the development of various tumors. This study explored whether circRNAs are involved in the progression of papillary thyroid carcinoma (PTC). METHODS: Differentially expressed circRNAs (DECs) in four pairs of PTC and matched normal thyroid tissues were screened using a circRNA microarray. The potential functions of dysregulated circRNAs were predicted by bioinformatic analyses. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to determine hsa_circ_0082003 expression in 80 pairs of PTC and matched normal thyroid tissues. Cell counting kit-8, colony formation, wound healing, and Transwell assays were performed to evaluate the biological functions of hsa_circ_0082003 in PTC cells. The role of hsa_circ_0082003 in PTC tumorigenesis in vivo was validated in nude mice. RESULTS: In total, 3150 DECs (2317 upregulated and 833 downregulated) were identified. Pathway enrichment analyses indicated that the dysregulated circRNAs may play roles in PTC development. RT-qPCR validation demonstrated that hsa_circ_0082003 expression was significantly increased in PTC tissues and correlated with poor clinicopathological parameters. Receiver operating characteristic curve analysis showed that hsa_circ_0082003 had good performance for diagnosing PTC and judging whether it was accompanied by lymph node metastasis. Knockdown of hsa_circ_0082003 inhibited PTC cell proliferation, migration, and invasion. Tumor formation assays in vivo showed that downregulation of hsa_circ_0082003 significantly suppressed the growth of PTC. CONCLUSION: Hsa_circ_0082003 may serve as a novel diagnostic biomarker and potential therapeutic target for PTC.