An open-label study of pemigatinib in cholangiocarcinoma: final results from FIGHT-202.

BACKGROUND: Fibroblast growth factor receptor 2 (FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a selective, potent, oral inhibitor of FGFR1-3 and demonstrated efficacy in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in FIGHT-202 (NCT02924376). We report final outcomes from the extended follow-up period. PATIENTS AND METHODS: The multicenter, open-label, single-arm, phase II FIGHT-202 study enrolled patients ≥18 years old with previously treated advanced/metastatic CCA with FGFR2 fusions or rearrangements (cohort A), other FGF/FGFR alterations (cohort B), or no FGF/FGFR alterations (cohort C). Patients received once-daily oral pemigatinib 13.5 mg in 21-day cycles (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) in cohort A assessed as per RECIST v1.1 by an independent review committee; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: FIGHT-202 enrolled 147 patients (cohort A, 108; cohort B, 20; cohort C, 17; unconfirmed FGF/FGFR alterations, 2). By final analysis, 145 (98.6%) had discontinued treatment due to progressive disease (71.4%), withdrawal by patient (8.2%), or adverse events (AEs; 6.8%). Median follow-up was 45.4 months. The ORR in cohort A was 37.0% (95% confidence interval 27.9% to 46.9%); complete and partial responses were observed in 3 and 37 patients, respectively. Median DOR was 9.1 (6.0-14.5) months; median PFS and OS were 7.0 (6.1-10.5) months and 17.5 (14.4-22.9) months, respectively. The most common treatment-emergent AEs (TEAEs) were hyperphosphatemia (58.5%), alopecia (49.7%), and diarrhea (47.6%). Overall, 15 (10.2%) patients experienced TEAEs leading to pemigatinib discontinuation; intestinal obstruction and acute kidney injury (n = 2 each) occurred most frequently. CONCLUSIONS: Pemigatinib demonstrated durable response and prolonged OS with manageable AEs in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in the extended follow-up period of FIGHT-202.

Effectiveness of different exercises in improving postural balance among Parkinson's disease patients: a systematic review and network meta-analysis.

Background: Exercise has been reported as an effective intervention for Parkinson's disease. However, there is still debate on the what kinds of exercises prior to choosing. This study aimed to compare and rank the different exercises that effectively enhance postural balance in Parkinson's disease patients by quantifying the information gleaned from randomized controlled trials (RCTs). Methods: We conducted a comprehensive database search, including PubMed, Cochrane Library, Embase, Web of Science, and PsycINFO. The included studies were evaluated for methodological quality by the Cochrane Risk of Bias tool. Results: The RCTs were collected between the earliest available date and March 2023. Sixty RCTs were included and the total sample size used in the study was 3,537. Thirty-five studies were defined as low risk of bias, twenty-one studies as medium risk of bias, and four studies as high risk of bias. The network meta-analysis results showed that exergaming exercise can significantly improve patients' Timed-Up-and-Go time (SUCRA = 91.5%). Dance can significantly enhance patients' Berg Balance Scale (surface under the cumulative ranking curve, SUCRA = 81.3%), and rhythmical auditory exercise can significantly improve patients' Mini-Balance Evaluation Systems Test score (SUCRA = 95.6%). Conclusion: Compared with other exercises, exergaming exercise, Dance, and rhythmical auditory exercise showed superior efficacy in improving postural balance among Parkinson's disease patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023411918.

[Parameningeal or non-parameningeal head and neck rhabdomyosarcoma: a study based on propensity score matching and survival analysis].

Objective: To compare the prognoses between parameningeal and non-parameningeal head and neck rhabdomyosarcoma based on propensity score matching and to explore the prognostic factors of overall survival in patients with head and neck rhabdomyosarcoma. Methods: The medical records of 64 patients with pathologically diagnosed as head and neck rhabdomyosarcoma from January 2016 to May 2020 in Peking Union Medical College Hospital were retrospectively retrieved, including 31 males and 33 females, with an average age of (8.0±8.9) years. Kaplan-Meier method was used to draw and compare survival curves in subgroup analysis according to different histopathological characteristics. Patients were divided into non-parameningeal (27 cases) and parameningeal (37 cases) group based on the location of primary lesion. Patients were further selected using 1∶1 propensity score matching method. The basic clinical data and overall survival were compared before and after matching. Prognostic factors were anlysed using Cox's proportional hazards regression model. Results: In 64 patients with head and neck rhabdomyosarcoma, lower risk stratification, and lower TNM stage indicated higher overall survival (all P<0.05). Before matching, patients in parameningeal group presented with higher T stage and IRS (Intergroup Rhabdomyosarcoma Study) staging (all P<0.05). There were no significant differences in basic clinical data and 1-, 2-, and 3-year overall survival rates between two groups after matching(P>0.05). Tumor size smaller than 5 cm, embryonal histology, negative FOXO1 fusion gene, lower risk stratification, and lower TNM stage were associated with higher overall survival (all P<0.05). Among these, tumor size and histology were independent prognostic factors (HR=2.36, 95%CI:1.07-5.20, P=0.033; HR=5.54, 95%CI: 1.18-25.95, P=0.030). Conclusions: There is no significant difference in overall survival between patients with parameningeal and non-parameningeal rhabdomyosarcomas. Tumor size smaller than 5 cm and embryonal histology are two independent prognostic factors.

[Efficacy and safety of Kangbingdu granules in the treatment of influenza: a randomized, double-blind, double-dummy, positive-drug parallel control multicenter clinical trial].

Objective: To observe the efficacy and safety of Kangbingdu granules (KBD) in the treatment of influenza. Methods: A multicenter, randomized, double-blind, double-dummy, and positive-drug parallel control trial was conducted in 27 Grade ⅢA hospitals in China and the subjects were randomly assigned to the KBD test group or the oseltamivir phosphate capsule control group at a ratio of 1∶1. 200 subjects were planned to be enrolled in each group. The experimental group was given KBD (18g each time, 3 times a day) and oseltamivir phosphate simulator orally, while the control group was given oseltamivir phosphate capsule (75 mg each time, twice a day) and KBD simulator orally for 5 days. The primary efficacy indicators included the remission time of major clinical symptoms and the time of complete defervescence. The secondary efficacy indicators included dosage of acetaminophen, the change of traditional Chinese medicine (TCM) syndrome score and the remission time of other important clinical symptoms. The efficacy of KBD in the test group and Oseltamivir phosphate control group were compared. Adverse events or adverse reactions were observed at the same time to evaluate the safety of KBD Granules. Results: A total of 393 subjects from 27 Grade ⅢA hospitals in China were enrolled. The experimental group included 195 subjects and 191 subjects (97.95%) completed the trial, While the control group included 198 subjects and 195 subjects (98.48%) completed the trial. There was no significant difference in the shedding rate and rejection rate between the two groups (P>0.05). In the Full Analysis Set (FAS), the mean age of the experimental group was (34.9±14.4) years old, with 83 males (42.78%). The mean age of the control group was (33.3±13.5) years old, with 78 males (39.59%). There were no statistically significant differences between the two groups in demographic data, physical examination, viral pathogen detection, total score of TCM syndromes and scores of each symptom at baseline (P>0.05). In the FAS, the remission time M (Q1, Q3) of major clinical symptoms was 3.0 (3.0, 4.0) days in the experimental group and 3.0 (3.0, 4.0) days in the control group, and the difference was not statistically significant (P>0.05). The time M (Q1, Q3) of complete defervescence was 34.0 (20.3, 49.0) hours in the experimental group and 36.5 (19.6, 48.8) hours in the control group, and the difference was not statistically significant (P>0.05). KBD granules had the same effect as Oseltamivir phosphate capsule (P>0.05) in terms of acetaminophen dosage, TCM syndrome effect and disappearance rate of most important clinical symptoms. Meanwhile, the disappearance rate of dizziness and chest distress on day 3 in the KBD granules group was better than that of oseltamivir phosphate capsule (P<0.05). Conclusion: KBD granules have the same efficacy as Oseltamivir Phosphate capsule in the treatment of influenza and the drug safety is good.

[Textual research on Xilei Powder].

Xilei Powder is a commonly used prescription for the treatment of oral ulcers, and is originally used to treat scarlet fever. Scarlet fever is a warm-toxin disease from the perspective of the theory of warm disease. It is a warm infectious disease caused by epidemic. Xilei Powder was recorded in the Chinese Pharmacopoeia from 1953 edition to 2010 edition. As China joined Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), Xilei Powder was removed from the Chinese Pharmacopoeia of 2015 edition due to the limitation of the use of animal drugs, such as ivory and rhinoceros horn. Xilei Powder has been widely used to treat such diseases as otolaryngology, fever, gynecological diseases, digestive diseases, and tumors. Does Xilei Powder have a unique place in clinical application? Can stable and effective alternative drugs be derived from original prescription? Due to the lack of theoretical studies on Xilei Powder, by consulting ancient books, monographs and papers, we comprehensively summarized and studied historical evolution and prescription connotation of Xilei Powder, and analyzed its drug origin and clinical application, in the hope to promote the theoretical study and clinical application.

A modified longitudinal incision via transoral sublabial approach for removal of the nasal vestibular cyst: a clinical observation.

OBJECTIVE: The aim of this study was to investigate the clinical effect of the removal of nasal vestibular cysts through a modified longitudinal incision via a transoral sublabial approach. METHOD: In 28 cases, a nasal vestibular cyst was removed through a modified longitudinal incision via a transoral sublabial approach. A visual analogue scale score was used to evaluate the numbness of the nasal alar and upper lip. Post-operative complications were recorded. Medical photographs were used for assessment. RESULTS: For all patients, incisions reached clinical primary healing one week after surgery. All patients were free of post-operative haematoma, infection, oronasal fistula and malformation. In the first week and the first month after surgery, numbness of the nasal alar and upper lip was recorded in few cases. The patients were followed up for 2-57 months without recurrence. CONCLUSION: Removal of nasal vestibular cysts via a transoral sublabial approach with a modified longitudinal incision is a minimally invasive and simple surgical method with few complications and a quick recovery.

Role of rural general surgeons in managing vascular surgical emergencies.

BACKGROUND: A rural general surgeon has historically been required to perform a wide variety of subspecialist procedures. Increasingly sub-specialized training programs have restricted younger surgeons' experience in the general surgery-associated subspecialties. Time critical vascular surgical emergencies are frequently encountered by rural general surgeons. This study aims to audit the prevalence of vascular surgical emergencies at a geographically remote regional centre and define the role of the general surgeon in managing these patients. METHODS: A single-centre, retrospective study was performed to analyse the outcomes of the patients who presented to Dubbo Base Hospital with an emergency vascular pathology or developed such a condition during admission, between October 2010 and June 2019. Patients were identified by relevant International classification of diseases (ICD) (10th revision) diagnostic codes for vascular emergencies. Acute complications following surgery for haemodialysis access were excluded. RESULTS: A total of 134 patients were identified during the study period and the majority were transferred to a tertiary centre for surgical intervention. Sixteen patients underwent emergency vascular surgery locally due to concerns about potential loss of life or limb if intervention was delayed by transfer; 69% of patients who underwent surgery locally survived with limb salvation. CONCLUSION: While most patients can safely be transferred to a tertiary centre, some require surgery locally in order to maximize chance of life or limb preservation. There is a strong argument for exposure of general surgical trainees with an interest in rural surgery to vascular surgery and other subspecialties.

[Application of image navigation assisted nasal endoscopic surgery in optic nerve decompression].

Objective:To explore the application and to evaluate the advantage of image navigation assisted nasal endoscopic surgery in optic nerve decompression. Method:Sixty patients accepted the image navigation assisted nasal endoscopic surgery therapy in optic nerve decompression were included in this retrospective study and followed up for about six months to four years. Result:The visual acuity was improved in 16 cases with visual acuity above light. One case is 10 cm index, two cases are 40 cm index, one case is 70 cm index, the visual acuity of rest 12 cases was between 0.04 and 0.30, two of them were missing from the field of view, the effective rate was 100%. The 44 cases without light sensation before operation, postoperative visual acuity was improved in 11 cases, four of which were light sensation and visible figure. Visual acuity of seven cases was between 0.03 and 0.08, one of them was missing from the field of view, the effective rate was 25%. No complications occurred. Conclusion:With the help of the image navigation, it is convenient and accurate to locate the anatomical marker sites such as orbital apex, optic canal and fracture site, internal carotid artery and so on, as a result, the accuracy and the success rate of the surgery were greatly improved.

Transoral and endoscope-assisted transoral approaches to resecting benign tumours of the parapharyngeal space located in the medial portion of the carotid sheaths and extending toward the skull base: our experience.

OBJECTIVE: Various surgical approaches have been described to remove tumours in the parapharyngeal space. This study investigated the feasibility of a transoral approach in the surgical management of parapharyngeal space benign tumours located in the medial portion of the carotid sheaths and extending toward the skull base. METHODS: Thirty-two patients were selected and underwent a transoral or an endoscope-assisted transoral approach in the surgical management of parapharyngeal space benign tumours located in the medial portion of the carotid sheaths. Medical photographs were used. RESULTS: All patients underwent complete resection of their lesions via a transoral or endoscope-assisted transoral approach. None of the patients demonstrated residual or recurrent neoplasms, either clinically or radiographically, during their follow up. CONCLUSION: Based on our studies, we assert that transoral and endoscope-assisted transoral approaches are suitable in managing parapharyngeal space benign tumours located in the medial portion of the carotid sheaths and extending toward the skull base.

[Wegner's granulomatosis of hypolarynx in a patient with laryngemphraxis: case report and review of literature].

Summary A patient suffered from progressive dyspnea and even laryngeal obstruction visited our department in May, 2017 and received emergency tracheotomy for assistance in breathing. There was no dysphagia, sore throat, fever, cough, hemoptysis and hematuresis. The pathological signs including facies dolorosa, three depressions sign, perforation of nasal septum. The laboratory examination showed that there were hematuresis and albuminuria. The urine bilirubin levels were elevated, antineutrophil cytoplasmic antibody (ANCA) was positive and antiproteinase 3 antibody was elevated. The electronic laryngoscope revealed the swelling of infraglottic region and laryngeal CT showed the subglottic area occupation and stenosis. The pulmonary CT showed the irregular mass shadow in lower lobe of right lung which was considered benign pathological changes. Finally, the diagnosis was subglottic Wegner's granulomatosis and result in laryngeal obstruction and need the first aid in clinic.

[Oncomelania hupensis status monitoring in Changzhou City, Jiangsu Province from 2013 to 2016].

Objective To analyze the Oncomelania hupensis snail distribution and the changes of snail situation in Changzhou City from 2013 to 2016, so as to provide the evidence for formulating the schistosomiasis prevention and control interventions. Methods The data of snail monitoring in Changzhou City from 2013 to 2016 were collected and statistically analyzed. Results The total area with snails was 40.17 hm2 and the newly discovered area was 30.63 hm2 in Changzhou City from 2013 to 2016. In the four years, 3 454 snails were dissected, and no schistosome infected snails were found. There were totally 51 spots with snails, and the areas with snails of different types of marshland, inland and mountain were 12.13 (30.19%), 25.54 hm2 (63.57%) and 2.51 hm2 (6.24%), respectively. In the newly discovered snail environment, the areas of types of marshland and inland were 8.00 hm2 (26.12%) and 22.63 hm2 (73.88%), respectively. The main causes for snail existence were external input and adjacent diffusion. In the past four years, the total snail control area with molluscicides was 71.74 hm2, the consolidated snail control area with molluscicides was 155.15 hm2, and the total environmental modification areas in the current snail spots and historic snail spots were 15.90 hm2 and 11.30 hm2 respectively. Conclusion The diffusion of snails in inland rivers is the key of the newly discovered snail areas in Changzhou City in recent years, and the snail monitoring and control measures should be strengthened in the future.

[Advances in treatment of locally advanced hypopharyngeal cancer].

Hypopharyngeal cancer is a common malignant tumor of otorhinolaryngology,which is considered to be one of the head and neck tumor with poor prognosis.Hypopharyngeal cancer is insidious in its onset and progresses rapidly,leading to significant delay in diagnosis; Most patients are in late stage at diagnosis. Surgery combined with chemoradiotherapy is the main treatment of locally advanced hypopharyngeal cancer. Biological treatment has drawn more and more attentions. In this paper,we summarize the progress in the treatment of locally advanced hypopharyngeal cancer.

Engineering and Optimization of Quasi-Nondiffracting Helicon-Like Beams With an Evolutionary Algorithm.

Nondiffracting beams maintain their intensity profiles over a large propagation distance without substantial diffraction and exhibit unique propagation trajectories, leading to scientific impacts in various fields. However, the nonlocalized intensity distribution of non-diffracting beams is restrictive for many practical applications. Thus, strategies to optimize the beam profiles remain much in demand. In this report, we demonstrate an evolutionary algorithmic framework for optical beam engineering and optimization and experimentally validate it by realizing quasi-nondiffracting radially self-accelerating (or self-rotating) beams in a high-resolution imaging system. The work reports a tightly confined side-lobe-suppressed helicon-like beam that largely maintains its properties of radial self-acceleration and non-diffraction in the 3-D space. The optimization method represents a new methodological avenue that can be extended to a broad range of beam engineering problems.

Thickness-induced structural phase transformation of layered gallium telluride.

The thickness-dependent electronic states and physical properties of two-dimensional materials suggest great potential applications in electronic and optoelectronic devices. However, the enhanced surface effect in ultra-thin materials might significantly influence the structural stability, as well as the device reliability. Here, we report a spontaneous phase transformation of gallium telluride (GaTe) that occurred when the bulk was exfoliated to a few layers. Transmission electron microscopy (TEM) results indicate a structural variation from a monoclinic to a hexagonal structure. Raman spectra suggest a critical thickness for the structural transformation. First-principle calculations and thermodynamic analysis show that the surface energy and the interlayer interaction compete to dominate structural stability in the thinning process. A two-stage transformation process from monoclinic (m) to tetragonal (T) and then from tetragonal to hexagonal (h) is proposed to understand the phase transformation. The results demonstrate the crucial role of interlayer interactions in the structural stability, which provides a phase engineering strategy for device applications.

[Hypopharyngeal angiofibroma: a case report].

Swallowing obstruction, gradually increase, with a sore throat, no fever, no haemoptysis, no dyspnea, routine tests: blood routine, biochemical examination, blood coagulation routine, electrocardiogram, chest X-ray, did not show abnormalities.

Down-regulated long non-coding RNA H19 inhibits carcinogenesis of renal cell carcinoma.

Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology. LncRNA H19 has been recently shown to be upregulated and play important roles in several cancers such as breast cancer, bladder cancer, and gastric cancer. However, the role of H19 in clear cell renal carcinoma (ccRCC) remains largely unknown.The expression levels of lncRNA H19 in ccRCC tissues and renal cancer cell lines were evaluated by quantitative Real-time PCR (qRT-PCR). And its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress H19 expression in renal cancer cell lines. In vitro assays were performed to further explore its role in tumor progression.The relative level of H19 was significantly higher in ccRCC compared to the adjacent normal renal tissues. And higher expression of H19 was found in renal cancer cells compared to the nonmalignant renal cells HK-2. Furthermore, The ccRCC patients with higher H19 expression had more advanced clinical stage and poorer prognosis than those with lower expression, Kaplan-Meier analysis revealed that patients with higher H19 expression had a poorer overall survival and H19 expression could be an independent prognostic marker for ccRCC patient. The results of in vitro assays indicated that knockdown of H19 reduced cell proliferation, invasion, and migration. Our data suggested that lncRNA H19 might be considered as a potential prognostic indicator and a target for gene therapy of ccRCC.

Effect of codon optimization on expression levels of human cystatin C in Pichia pastoris.

Human cystatin C (CysC) is a cysteine proteinase inhibitor with many potential applications. To facilitate further studies of the functions and applications of CysC, we improved the heterologous expression of CysC using a basic codon optimization method. In this study, we cloned the high-GC content wild-type sequence of the CysC gene and also designed a slightly AT-biased sequence, with codons optimized for expression in the Pichia pastoris GS115 strain. Our results showed that the optimized coding sequence of human CysC increased the expression and secretion of the CysC protein by approximately 3- to 5-fold (90-96 mg CysC/L) in yeast, compared with the expression levels of the native CysC gene (17.9-18.4 mg CysC/L). We designed, constructed, and applied an optimized version of the CysC gene for the Pichia expression system. Our results demonstrate that the optimized coding sequence provides a higher yield of secreted CysC than that produced using the wild-type gene. Our data also serve as a practical example demonstrating a rational design strategy for the heterologous expression of secreted proteins.

Primary intraosseous ACC of mandible of possible salivary origin: A rare clinical entity.

INTRODUCTION: Adenoid cystic carcinoma (ACC) is a malignant tumor mainly of salivary origin which is well known for its deceptively benign histologic appearance characterized by indolent, locally invasive growth with high propensity for local recurrence and distant metastasis. PRESENTATION OF CASE: An unusual case of a 23-year-old woman was reported in our hospital. After investigations, it showed that it is a second primary intraosseous lesion of mandible that occurred subsequently after ACC of parotid gland. After diagnosis was established, resection of tumor and reconstruction with a free fibula flap was performed. Ten months follow-up showed no signs of recurrence or metastasis. DISCUSSION: Among the salivary neoplasms, adenoid cystic carcinoma is very rare and intraosseous lesions are even rarer. We found a total of 26 cases of primary ACC of the mandible reported in the literature. Pain and swelling were the most frequent symptoms. CONCLUSION: This case illustrates two key facts. First, not all cystic lesions are necessarily metastatic or recurrence. Second is, even though the exact origin of this tumor is unknown, central salivary gland tumors should be considered in the differential diagnosis of cystic lytic lesions in the mandible.

The prevalence and risk factors of OAB in middle-aged and old people in China.

AIMS: To evaluate the prevalence of associated risk factors of over active bladder (OAB) in people ≥40 years old in mainland of China. METHODS: A randomized community-based, cross-sectional study was performed on 10,160 residents (≥40 years old) in the mainland of China using a questionnaire. The overactive bladder symptom score (OABSS) was filled upon site. The chi-square test was used to determine the differences of prevalence between sex, age groups, body mass index (BMI) and people with and without diabetes mellitus (DM). RESULTS: A total of 9,805 (96.5%) subjects qualified for the final statistical analysis. The overall prevalence of OAB was 2.1% (209/9,805), of whom 1.0% had OABdry and 1.1% had OABwet . The prevalence of OAB was more common in men than in women over the age of 60 (4.6% vs. 2.6%, P < 0.05). The prevalence of OAB in subjects with DM was significantly higher than those without DM in patients with BMI ≥ 25 (P < 0.05). The subjects with a BMI over 29 were more likely to have OAB (3.2% vs. 1.8%, P < 0.05). CONCLUSIONS: In this population, the prevalence of OAB increased with age for both sexes, but was higher for males over 60 years of age. The study also showed that diabetics with BMI ≥ 25 and people suffering from obesity are more likely to have OAB.