[Application of modified urethral separation method in artificial urethral sphincter implantation and its influence on intraoperative urethral pressure profilometry].

Objective: To explore the application of modified urethral separation method in artificial urethral sphincter (AUS) implantation in patients with stress urinary incontinence (SUI), and its influence on the results of urethral pressure profilometry. Methods: A prospective collection of clinical data was conducted on 25 patients with stress urinary incontinence who underwent modified urethral separation method in AUS implantation and underwent urethral pressure profilometry in Beijing Hospital, Beijing Jishuitan Hospital Affiliated to Capital Medical University and the Second Hospital Affiliated to Tianjin Medical University from March 2019 to June 2023. The improved urethral separation method was to borrow part of the white membrane tissue of the cavernous body while freeing the dorsal side of the cavernous body of the urethra. The circumference of the urethra, sleeve size, and urethral pressure were recorded, the patient's autonomous urinary control before and after surgery and the changes of the international consultation on incontinence questionnaire-short form (ICI-Q-SF) score, incontinence quality of life questionnaire (I-QoL) score, urinary frequency score, nocturia score were compared. Follow-up was conducted in the clinic or by telephone at 1, 3, 6, and 12 months after activation of the device, and once a year thereafter. Local skin status and urine control were assessed, residual urine volume was measured by ultrasound and subjective score scale was completed. Results: All patients were male, aged 27-85 (65.8±15.7) years old. The circumference of the cuff used in this study was 4.0 cm in 4 patients (16.0%), 4.5 cm in 16 patients (64.0%), 5.0 cm in 4 patients (16.0%), and 5.5 cm in 1 patient (4.0%). Among them, the urethral circumference matched the cuff size in 14 cases (56.0%), the urethral circumference was smaller than the cuff size in 4 cases (16.0%), and the urethral circumference was larger than the cuff size in 7 cases (28.0%). Preoperative urodynamic examination showed that the maximum urethral pressure (MUP) was (78.0±25.9) cmH2O, (1 cmH2O=0.098 kPa) and the maximum urethral closure pressure (MUCP) was (53.4±26.6) cmH2O. The MUP of AUS device in the inactivated state was (88.0±26.5) cmH2O, which was not significantly higher than that before operation (P>0.05). The MUCP was (68.2±24.5) cmH2O, which was significantly higher than that before operation (P<0.05). The MUP and MUCP of the AUS device in the activated state were (146.6±25.2) cmH2O and (123.0±28.3) cmH2O, which were significantly higher than those before surgery and in the inactivated state (both P<0.001). All patients in the group reached the social urinary control standards at the first month of device activation. During a follow-up period of 2-50 months, 22 patients (88.0%) used the initial AUS device and all met social urinary control standards. The AUS device was replaced in 1 case. One patient died of cerebrovascular accident. One patient removed the device due to complications. The number of pads [M (Q1, Q3)] used in 25 patients before and after operation was 4.5 (3.0, 6.5) and 1 (0, 1) respectively, with statistically significant differences (P<0.001). ICI-Q-SF score, I-QoL score, urinary frequency score and nocturia score of 25 patients were significantly improved after surgery (all P<0.05). The incidence of postoperative complications was 20.0% (5/25), including 2 cases of painless hematuria, 1 case of infection, 1 case of urethral erosion, and 1 case of dysuria. Except for one patient who experienced urethral erosion and had his sleeve removed, the remaining four patients regained social urination control with active support treatment, and no symptoms recurred until the last follow-up. Conclusion: The modified urethral separation method has no significant effect on urethral pressure in patients with SUI, and can increase the volume of peri-urethral tissue in the cuff, thereby reducing the risk of intraoperative urethral injury and the incidence of postoperative urethral erosion.

[Antitumor effects of redox-responsive nanoparticles containing platinum（⠣）in ovarian cancer].

Objectives: To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)-NP@Pt(Ⅳ) in ovarian cancer. Methods: Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)-Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured. Results: The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment (P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 µmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 µmol/L) and cisplatin (5.21, 11.85, and 71.98 µmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm3, which was significantly lower than those in control group [(1 349±161) mm3, P<0.001] and cisplatin group [(715±293) mm3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion: Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

Quantitative biodistribution of nanoparticles in plants with lanthanide complexes.

The inefficient distribution of fertilizers, nutrients, and pesticides on crops is a major challenge in modern agriculture that leads to reduced productivity and environmental pollution. Nanoformulation of agrochemicals is an attractive approach to enable the selective delivery of agents into specific plant organs, their release in those tissues, and improve their efficiency. Already commercialized nanofertilizers utilize the physiochemical properties of metal nanoparticles such as size, charge, and the metal core to overcome biological barriers in plants to reach their target sites. Despite their wide application in human diseases, lipid nanoparticles are rarely used in agricultural applications and a systematic screening approach to identifying efficacious formulations has not been reported. Here, we developed a quantitative metal-encoded platform to determine the biodistribution of different lipid nanoparticles in plant tissues. In this platform lanthanide metal complexes were encapsulated into four types of lipid nanoparticles. Our approach was able to successfully quantify payload accumulation for all the lipid formulations across the roots, stem, and leaf of the plant. Lanthanide levels were 20- to 57-fold higher in the leaf and 100- to 10,000-fold higher in the stem for the nanoparticle encapsulated lanthanide complexes compared to the unencapsulated, free lanthanide complex. This system will facilitate the discovery of nanoparticles as delivery carriers for agrochemicals and plant tissue-targeting products.

[Ascites CD100 levels and immunomodulation effects in the peripheral blood of patients with liver cirrhosis combined with spontaneous bacterial peritonitis].

Objective: To observe the level and detection of ascites CD100 on the activity of CD4(+) and CD8(+) T lymphocytes in vitro in the peripheral blood of patients with liver cirrhosis combined with spontaneous bacterial peritonitis. Methods: Peripheral blood and ascites were collected from 77 cases of liver cirrhosis (49 patients with liver cirrhosis combined with simple ascites and 28 patients with liver cirrhosis combined with SBP), and peripheral blood was collected from 22 controls. Soluble CD100 (sCD100) in peripheral blood and ascites was detected by an enzyme-linked immunosorbent assay. Flow cytometry was used to detect membrane-bound CD100 (mCD100) on the surface of CD4(+) and CD8(+)T lymphocytes. CD4(+) and CD8(+)T lymphocytes in ascites were sorted. CD4(+)T lymphocyte proliferation, key transcription factor mRNA, and secreted cytokine changes, as well as CD8(+)T lymphocyte proliferation, important toxic molecule mRNA, and secreted cytokine changes, were detected after CD100 stimulation. The killing activity of CD8(+)T cells was detected by direct contact and indirect contact culture systems. Data conforming to normality were compared using one-way ANOVA, a student's t-test, or a paired t-test. Data that did not conform to a normal distribution were compared using either the Krusal-Willis test or the Mann-Whitney test. Results: There was no statistically significant difference in plasma sCD100 level between patients with liver cirrhosis combined simple ascites (1 415 ± 434.1) pg/ml, patients with liver cirrhosis combined with SBP (1 465 ± 386.8) pg/ml, and controls (1 355 ± 428.0) pg/ml (P = 0.655). The ascites sCD100 level was lower in patients with liver cirrhosis combined with SBP than that of patients with simple ascites [(2 409 ± 743.0) pg/ml vs. (2825±664.2) pg/ml, P=0.014]. There was no statistically significant difference in the level of mCD100 in peripheral blood CD4(+) and CD8(+) T lymphocytes among the three groups (P > 0.05). The levels of mCD100 in ascites CD4(+) and CD8(+) T lymphocytes were higher in patients with liver cirrhosis combined with SBP than those in patients with simple ascites (P < 0.05). CD100 stimulation had no significant effect on the proliferation of CD4(+) and CD8(+)T lymphocytes in the ascites of patients with liver cirrhosis combined with SBP (P > 0.05). There were no significant effects on the expression of transcription factors in effector CD4(+)T lymphocytes (T-bet, retinoic acid associated solitary nuclear receptor γt, aromatic hydrocarbon receptor) or secretion of cytokines (interferon-γ, 17, and 22) (P > 0.05). CD100 stimulation had increased the relative expression of perforin, granzyme B, and granlysin mRNA and the levels of secreted interferon-γ and tumor necrosis factor-α, killing activity in ascites CD8+ T lymphocytes of patients with liver cirrhosis combined with SBP (P < 0.05). Conclusion: The active form of CD100 is sCD100 instead of mCD100. There is an imbalance between the expression of sCD100 and mCD100 in the ascites of patients with cirrhosis combined with SBP. sCD100 can enhance the function of CD8(+)T lymphocytes in the ascites of patients with cirrhosis combined with SBP and thus is one of the potential therapeutic targets.

Gender equity of authorship in pulmonary medicine over the past decade.

BACKGROUND: Gender disparity in authorship broadly persists in medical literature, little is known about female authorship within pulmonary medicine. METHODS: A bibliometric analysis of publications from 2012 to 2021 in 12 journals with the highest impact in pulmonary medicine was conducted. Only original research and review articles were included. Names of the first and last authors were extracted and their genders were identified using the Gender-API web. Female authorship was described by overall distribution and distribution by country/region/continent and journal. We compared the article citations by gender combinations, evaluated the trend in female authorship, and forecasted when parity for first and last authorship would be reached. We also conducted a systematic review of female authorship in clinical medicine. RESULTS: 14,875 articles were included, and the overall percentage of female first authors was higher than last authors (37.0% vs 22.2%, p<0.001). Asia had the lowest percentage of female first (27.6%) and last (15.2%) authors. The percentages of female first and last authors increased slightly over time, except for a rapid increase in the COVID-19 pandemic periods. Parity was predicted in 2046 for the first authors and 2059 for the last authors. Articles with male authors were cited more than articles with female authors. However, male-male collaborations significantly decreased, whereas female-female collaborations significantly increased. CONCLUSIONS: Despite the slow improvement in female authorship over the past decade, there is still a substantial gender disparity in female first and last authorship in high-impact medical journals in pulmonary medicine.

[Signal transducer and activator of transcription 3 and cancer associated fibroblasts jointly generate chemo-resistance and affect prognosis in epithelial ovarian cancer].

Objective: To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3) and cancer associated fibroblasts (CAF) jointly generate chemo-resistance in epithelial-ovarian cancer and their effect on prognosis. Methods: A total of 119 patients with high-grade ovarian serous cancer who received surgery in Cancer Hospital of Chinese Academy of Medical Sciences from September 2009 to October 2017 were collected. The clinico-pathological data and follow-up data were complete. Multivariate Cox regression model was used to analyze the prognostic factors. Ovarian cancer tissue chips of patients in our hospital were prepared. EnVision two-step method immunohistochemistry was used to detect the protein expression levels of STAT3, the specific markers of CAF activation, fibroblast activating protein (FAP), and type Ⅰ collagen (COL1A1) secreted by CAF. The relationship between the expression of STAT3, FAP, COL1A1 protein and drug resistance and prognosis of ovarian cancer patients was analyzed, and the correlation between the expression of three proteins was analyzed. These results were verified through the gene expression and prognostic information of human ovarian cancer tissues collected in the GSE26712 dataset of gene expression omnibus (GEO) database. Results: (1) Multivariate Cox regression model analysis showed that chemotherapy resistance was an independent risk factor for overall survival (OS) of ovarian cancer (P<0.001). (2) The expression levels of STAT3, FAP, and COL1A1 proteins in chemotherapy resistant patients were significantly higher than those in chemotherapy sensitive patients (all P<0.05). Patients with high expression of STAT3, FAP, and COL1A1 had significantly shorter OS than those with low expression (all P<0.05). According to the human ovarian cancer GSE26712 dataset of GEO database, patients with high expression of STAT3, FAP, and COL1A1 also showed shorter OS than patients with low expression (all P<0.05), the verification results were consistent with the detection results of ovarian cancer patients in our hospital. (3) Correlation analysis showed that the protein level of STAT3 was positively correlated with FAP and COL1A1 in our hospital's ovarian cancer tissue chips (r=0.47, P<0.001; r=0.30, P=0.006), the analysis of GEO database GSE26712 dataset showed that the expression of STAT3 gene and FAP, COL1A1 gene were also significantly positively correlated (r=0.31, P<0.001; r=0.52, P<0.001). Conclusion: STAT3 and CAF could promote chemotherapy resistance of ovarian cancer and lead to poor prognosis.

[Mid-term outcome of deep layer repair with the long head of the biceps autograft bridging for Kim classification type â A delaminiated rotator cuff tear].

Objective: To investigate the mid-term clinical outcome of deep layer repair with the long head of the biceps autograft bridging for Kim classification type ⅠA delaminated rotator cuff tear. Methods: A follow-up study. The clinical data of 42 consecutive patients with Kim classification type ⅠA delaminated rotator cuff tear admitted to the First Affiliated Hospital of Jinan University from January 2018 to June 2019 were retrospectively included. All patients underwent shoulder arthroscopic surgery. During the operation, the autogenous long head of the biceps tendon was transferred to repair the deep layer of delaminated rotator cuff tear. The preoperative and postoperative (last follow-up) visual analogue scale (VAS) for pain, University of California Los Angeles (UCLA) score, Constant-Murley shoulder score, range of motion (ROM) of the shoulder and radiographic results were statistically analyzed. Results: A total of 42 patients were included in this study. There were 18 males and 24 females, with an average age of (64.5±15.2) years and a mean follow-up of (43.9±7.1) months. At the last follow-up, ROM of abduction increased from 80.8°±26.5° to 154.2°±14.3°, and ROM of external rotation increased from 18.2°±13.6° to 31.8°±7.8°; the VAS score of pain decreased from (5.5±1.3) points to (0.7±0.7) points, the UCLA score increased from (21.3±3.7) points to (29.9±2.1) points, and the Constant-Murley score increased from (45.4±10.0) points to (87.2±4.8) points; the differences were all statistically significant (all P<0.001). The X-ray films showed that there were no upward of the humeral head in all the patients. MRI results indicated that rotator cuff re-teared in one case (Sugaya classification type Ⅲ), and healed in other cases (Sugaya classification type Ⅰ-Ⅱ). No complications such as upper limb nerve injury was found in all cases. Conclusion: Deep layer repair with the long head of the biceps autograft bridging can significantly alleviate the pain and improve the function of patients with Kim classification type ⅠA delaminated rotator cuff tear, and the incidence of retear is low.

[Identification of Stigma Specific Expression Fragment in the Promoter of a Soybean Chitinase Class I Gene].

The expression level of heterologous genes in transgenic plants serves as an important indicator of gene efficiency. The small number of currently known effective promoters, limits the possibilities in fine-tuning the expression of transgenes. We cloned and characterized a tissue-specific promoter fragment of the soybean chitinase class I gene (GmChi1). The GmChi1 promoter (GmChi1P) was cloned from Jungery soybean. The promoter sequence contains a number of putative cis-acting elements, including tissue-specific and stress-regulated motifs. By histochemical analysis, the GmChi1P-controlled ß-glucuronidase (GUS) reporter enzyme activity was shown to be highest in the roots of transgenic Nicotiana tabacum cv. NC89 at the four-leaf sprout formation stage. Interestingly, the high GUS activity in transgenic tobacco roots was effectively suppressed by salicylic acid (SA) treatment. Deletion analysis of GmChi1P revealed that the sequences located between positions -719 and -382 contain key cis-elements responsible for the reporter uidA gene expression (encoding GUS) in leaves, roots, and wounds of Nicotiana tabacum. In addition, fluorometric analysis showed that the activity of the shortened ChiP(-1292) to ChiP(-719) promoters in the roots of transgenic tobacco was significantly suppressed by abscisic acid and completely suppressed by SA. The ChiP(-382) promoter was also found to be expressed exclusively in the stigma of transgenic tobacco flowers. Using the GUS reporter enzyme, no staining was detected in other flower organs in transgenic Nicotiana tabacum, including sepals, petals, anthers, filaments, and ovaries, or in any vegetative tissues. The results indicate that the promoter fragment ChiP(-382) can be used in tissue-specific regulation of gene expression and plant genetic engineering.

MTHFR C677T polymorphism, homocysteine, burden, and location of AMI and ACI.

OBJECTIVE: We aimed to investigate the relationship between homocysteine levels and MTHFR C677T polymorphisms and acute ischemic vascular events and focused on the differential effects of the MTHFR C677T polymorphisms on the burden and location of AMI and ACI. PATIENTS AND METHODS: 102 acute cerebral infarction (ACI) and acute myocardial infarction (AMI) patients who were admitted to the First Hospital of Jilin University in northeast China as the patient group, 83 healthy people who were hospitalized during the same period served as a control group. MTHFR C677T genotypes were identified via Polymerase Chain Reaction (PCR)-Fluorescent Probe Method. RESULTS: Patient group had higher serum homocysteine levels (p=0.013), lower serum folic acid (p<0.001), and Vit B12 levels (p=0.004) compared to the control group. Homocysteine levels in the patient group with the TT genotypes of the MTHFR C677T polymorphisms were higher than those with the CC and CT genotypes (p<0.05). Folic acid levels in the patients with TT genotypes were lower than those with the CC genotypes (p<0.05), but not in the control group (p>0.05). There were negative and significant associations between serum homocysteine levels and serum vitamin B12 levels in the control group (r=-0.234, p=0.033), but not between serum homocysteine levels and serum folic acid levels (r=-0.103, p=0.355). Conversely, there was a negative and significant association between serum homocysteine levels and serum folic acid levels in the patients' group (r=-0.257, p=0.01), but not between serum homocysteine levels and serum vitamin B12 levels (r=-0.185, p=0.64). No statistically significant differences in MTHFR C677T genotype and C/T alleles distribution were investigated between the patient and control group (p>0.05). The MTHFR C677T polymorphism did not differentially affect the burden and location of AMI and ACI. CONCLUSIONS: Homocysteine played a common role in atherosclerosis-related acute ischemic vascular events. These correlations were modified by MTHFR C677T polymorphisms and influenced by folic acid levels. The MTHFR C677T polymorphisms were not directly related to acute ischemic vascular events, nor did they differentially affect the burden and location of AMI and ACI.

[Role of preoperative ultrasound-guided inferior parathyroid gland localization and new classification to assist intraoperative search and protection of parathyroid glands].

Objective: To investigate the role and significance of ultrasound-guided inferior parathyroid gland (IPTG) localization in searching and protecting parathyroid glands before thyroid surgery. Methods: A randomized controlled trial study was conducted. A total of 306 patients (433 cases of lateral parathyroidectomy) who underwent primary thyroidectomy and central lymph node dissection in Beijing Tongren Hosipital from March to October 2021 were enrolled. In order to locate IPTG more quickly and effectively, new IPTG classification and the definition of quadrant position were carried out. The patients were divided into the study group (n=228) and the control group (n=205). The study group underwent ultrasound-guided IPTG examination before operation and measured the distance between the IPTG and the lower pole of the thyroid and the midline of the trachea. During the operation, the IPTG was found and protected depending on the localization. The control group did not use any auxiliary preoperative positioning method. The distribution ratio of IPTG and the coincidence rate between intraoperative validation and ultrasound localization were calculated. Results: There were 306 patients enrolled in the final analysis (95 males and 211 females), with a median age of 41 years old (18-70). Type Ⅱ and Ⅲ IPTG accounted for 77.2% (176/228) of the total cases. The total coincidence rate ranged from 72.8% to 79.4% in different IPTG groups. Type Ⅲ and quadrant 2 IPTG had the highest coincidence rate [92.4% (73/79) and 92.9% (79/85), respectively]. The study group had better in situ retention rate [82.0% (187/228) vs 73.2% (150/205), χ2=4.896, P=0.027] and less implantation rate [8.8% (20/228) vs 16.1% (33/205), χ2=5.393, P=0.020] than those of the control group. The in situ retention rate were better in type Ⅲ IPTG group, compared with those of the control group [94.9% (74/78) vs 77.4% (48/62), χ2=7.898, P=0.005]. There was no permanent hypoparathyroidism in two groups and the temporary hypoparathyroidism rate was 32.0% (24/75) and 34.6% (18/52), respectively (χ2=0.095, P=0.758). Conclusion: Ultrasound-guided IPTG localization examination has important implications for searching and protecting IPTG during operation, which can significantly increase in situ retention rate of IPTG and decrease the implantation rate.

[Risk factors for recurrence and survival analysis in locally advanced T4a papillary thyroid carcinoma after R0 resection].

Objective: To investigate the treatment outcomes and risk factors of postoperative recurrence in T4a papillary thyroid carcinoma (PTC). Methods: A total of 185 patients with locally advanced T4a PTC treated in Beijing Tongren Hospital, Capital Medical University from January 2006 to December 2019 were retrospectively analyzed, including 127 females and 58 males, aged between 18 and 80 years, with 74 patients aged over 55 years. According to AJCC thyroid tumor staging, 111 cases were stage I (T4aN0M0 26 cases, T4aN1aM0 35 cases, and T4aN1bM0 50 cases) and 74 cases were stage Ⅲ (T4aN0M0 29 cases, T4aN1aM0 19 cases, and T4aN1bM0 26 cases). Kaplan-Meier method was used to calculate the overall survival and the recurrence-free rate, and univariate and multivariate logistic regression analyses on the clinical data were performed. Results: Recurrent laryngeal nerve invasion was observed in 150 cases, trachea invasion in 61 cases, esophagus invasion in 30 cases, and laryngeal structure invasion in 10 cases. Postoperative follow-up periods were 24-144 months, with an average of 68.29 months. Of the 185 patients, 18 (9.73%) had recurrences or metastases, including 9 cases (4.86%) died of recurrences or metastases. The 5-year and 10-year overall survival rates were respectively 95.21% and 93.10%. The 5-year and 10-year disease-free survival rates were respectively 89.65% and 86.85%. Univariate analysis showed that age of onset, tumor diameter, preoperative recurrent laryngeal nerve palsy, esophageal invasion and cervical lymph node metastasis were the risk factors for postoperative recurrence of T4a PTC(all P<0.05). Multivariate analysis showed that preoperative recurrent laryngeal nerve palsy (OR=3.27, 95%CI: 1.11-9.61, P=0.032) and lateral cervical lymph node metastasis (OR=4.71, 95%CI: 1.19-18.71, P=0.027) were independent risk factors for T4a PTC recurrence. Survival rate of patients with T4a PTC involving only the recurrent laryngeal nerve or the outer tracheal membrane was significantly better than that of patients with tracheal invasion (P<0.05). Conclusions: T4a PTC patients with R0 resection can still achieve good efficacy. Preoperative recurrent laryngeal nerve palsy and lateral cervical lymph node metastasis are independent risk factor for postoperative recurrence in the patients.

[Bipolar androgen therapy followed by immune checkpoint inhibitors in metastatic castration resistant prostate cancer: A report of 4 cases].

The relationship between androgen and prostate cancer treatment has plagued the field of urologic oncology. To investigate the efficacy and safety of bipolar androgen therapy (BAT) followed by immune checkpoint inhibitor therapy in patients with metastatic castration resistant prostate cancer (mCRPC). In August 2020, Beijing Hospital conducted an investigator-initiated study: Bipolar androgen therapy followed by immune checkpoint inhibitor therapy in metastatic castration resistant prostate cancer. Up to now, the study has included 4 patients who completed the entire cycle of treatment. The mean age of the patients was 74.5 (68 to 82) years old, the mean prostate-specific antigen (PSA) was 20.8 (9.9 to 8.36) µg/L, the mean testosterone was 0.50 (0.00 to 1.81) µg/L, and the Gleason score were 10 and 9, 7, 7 respectively. The pain scale score before treatment was 1.5 (1 to 2). In this study, 4 patients completed the entire cycle of treatment, and the treatment effect of the patients showed great heterogeneity. PSA in case 1 decreased from 24.0 µg/L to 0.47 µg/L, testosterone increased from 0.175 6 µg/L to 2.62 µg/L. PSA in case 2 increased from 9.939 µg/L to 168.536 µg/L, and testosterone increased from 0.0 µg/L increased to 2.85 µg/L. PSA increased from 13.31 µg/L to 39.278 µg/L in case 3, testosterone increased from 0.0 µg/L to 2.54 µg/L. and PSA increased from 36.0 µg/L to 350.2 µg/L in the case 4, testosterone increased from 1.81 µg/L to 3.85 µg/L. Except for one patient who showed significant PSA remission, the PSA levels of the remaining three patients remained high overall. There were no adverse reactions reported in 4 patients. In the follow-up, case 1 continued to use PD-1 monoclonal antibody (median progression free survival time was 10 months). Two patients who had previously been resistant to enzalutamide received enzalutamide again after the whole cycle of treatment, and their PSA decreased again, which indicated that the patient was sensitive to enzalutamide again. BAT had a certain therapeutic effect on mCRPC patients, and the safety was controllable. Its tumor control effect still needed long-term follow-up verification in large-sample clinical trials. BAT has a certain therapeutic effect on mCRPC patient, especially the resensitivity of tumors to enzalutamide can be restored. Immune checkpoint inhibitors may have therapeutic potential in patients with prostate cancer treated with BAT and enzalutamide.

Sex differences in the mouse photothrombotic stroke model investigated with X-ray fluorescence microscopy and Fourier transform infrared spectroscopic imaging.

Stroke is a leading cause of death and disability around the world. To date, the majority of pre-clinical research has been performed using male lab animals and results are commonly generalized to both sexes. In clinical stoke cases females have a higher incidence of ischemic stroke and poorer outcomes, compared to males. Best practices for improving translatability of findings for stroke, encourage the use of both sexes in studies. Since estrogen and progesterone have recognized neuroprotective effects, it is important to compare the size, severity and biochemical composition of the brain tissue following stroke in female and male animal models. In this study a photothrombotic focal stroke was induced in male and female mice. Vaginal secretions were collected twice daily to track the stage of estrous. Mice were euthanized at 24 h post-stroke. Histological staining, Fourier transform infrared imaging and X-ray fluorescence imaging were performed to better define the size and metabolic markers in the infarct core and surrounding penumbra. Our results show while the female mice had a significantly lower body mass than males, the cross-sectional area of the brain and the size of infarct and penumbra were not significantly different between the groups. In addition to the general expected sex-linked differences of altered NADH levels between males and females, estrus females had significantly elevated glycogen in the penumbra compared with males and total phosphorus levels were noted to be higher in the penumbra of estrus females. Elevated glycogen reserves in the tissue bordering the infarct core in females may present alternatives for improved functional recovery in females in the early post-stroke phase.

[Analysis of the diagnosis and treatment of patients with SMARCB1 (INI-1)-deficient sinonasal carcinoma].

Objective: To summarize the clinical features, treatments and outcomes of patients with SMARCB1(INI-1)-deficient sinonasal carcinoma (SDSC). Methods: Fifteen patients who were diagnosed as SDSC in Beijing Tongren Hospital from October 2016 to June 2021 were retrieved, including nine males and six females, ranged from 25 to 78 years old. For TNM stage, one case was in stage T2, one case was in stage T3, 13 cases were in stage T4; 13 cases were in stage N0, two cases were in stage N2; 14 cases were in stage M0, one case was in stage M1. The most common paranasal sinus affected by tumor was the ethmoid sinus. Five patients were treated by radical surgical resection combined with postoperative adjuvant therapy, four patients treated by neoadjuvant therapy with surgical resection, three patients treated by surgical resection only, one patient treated by neoadjuvant therapy with concurrent chemoradiotherapy, one patient treated by preoperative radiotherapy with surgery, and one patient received palliative chemotherapy. Immunohistochemical analysis was performed in all cases. The Kaplan-Meier method was used to draw the survival curve, and the Log-rank test was used to compare the difference to 20 undifferentiated carcinoma patients with positive INI-1 expression in the same period. Results: Immunohistochemical analysis showed the complete absence of INI-1 expression in the tumor nuclei in all 15 cases. The follow-up information was available with a median follow-up time of 21 months (3-56 months). The 3-year overall survival rate, disease specific survival rate, disease-free survival rate and metastasis-free survival rate were 58.9%, 58.9%, 36.4% and 31.2%, respectively. Disease-free survival in SDSC patients was significantly lower compared with undifferentiated carcinoma patients with positive INI-1 expression (HR=2.87,95%CI:0.92~8.91,P=0.043). Cox regression analysis showed that patients with comprehensive treatment based on surgery had a better prognosis than others (HR=8.61,95%CI:1.38~53.73,P=0.021). Conclusion: SDSC is a highly aggressive malignant tumor with the characteristics of easy recurrence, early metastasis and poor prognosis. INI-1 immunohistochemical analysis is recommended in the pathologically poorly differentiated sinonasal carcinoma. Comprehensive treatment based on radical resection may be the first choice for SDSC patients.

Multimodal imaging of hemorrhagic transformation biomarkers in an ischemic stroke model.

Hemorrhagic transformation of ischemic stroke has devastating consequences, with high mortality and poor functional outcomes. Animal models of ischemic stroke also demonstrate the potential for hemorrhagic transformation, which complicates biochemical characterization, treatment studies, and hinders poststroke functional outcomes in affected subjects. The incidence of hemorrhagic transformation of ischemic stroke in animal model research is not commonly reported. The postmortem brain of such cases presents a complex milieu of biomarkers due to the presence of healthy cells, regions of varying degrees of ischemia, dead and dying cells, dysregulated metabolites, and blood components (especially reactive Fe species released from lysed erythrocytes). To improve the characterization of hemorrhage biomarkers on an ischemic stroke background, we have employed a combination of histology, X-ray fluorescence imaging (XFI), and Fourier transform infrared (FTIR) spectroscopic imaging to assess 122 photothrombotic (ischemic) stroke brains. Rapid freezing preserves brain biomarkers in situ and minimizes metabolic artifacts due to postmortem ischemia. Analysis revealed that 25% of the photothrombotic models had clear signs of hemorrhagic transformation. The XFI and FTIR metabolites provided a quantitative method to differentiate key metabolic regions in these models. Across all hemorrhage cases, it was possible to consistently differentiate otherwise healthy tissue from other metabolically distinct regions, including the ischemic infarct, the ischemic penumbra, blood vessels, sites of hemorrhage, and a region surrounding the hemorrhage core that contained elevated lipid oxidation. Chemical speciation of deposited Fe demonstrates the presence of heme-Fe and accumulation of ferritin.

Significance of soil moisture on temperature dependence of Hg emission.

Soil moisture is a key factor for mercury (Hg) emission from soil. Despite its significance for Hg emissions, the effect of soil moisture on Hg flux and fractions has not been thoroughly investigated. The objective of this study was to elucidate the influences of soil moisture and temperature on Hg fluxes from soils and Hg fractions. A kinetic study was performed to measure Hg emission fluxes of six soil samples under different temperature (T) (15 °C, 20 °C, 25 °C, 30 °C, and 35 °C) and moisture conditions (0%, 10%, and 20% added water). The results showed that the Hg fluxes increased with increases in T and soil moisture. A linear correlation was found between ln (Hg emission flux) and 1/T for the six soil samples at different moisture contents (R2 = 0.73-0.99). The range of activation energy (Ea) values was 25.31-57.86 kJ/mol. The Hg fractions in soils of different moisture content were determined by a sequential extraction method. The results demonstrated that soil moisture affected the Hg fractions in soils. The Ea values had different relationships with soil moisture in different soils. There were correlations between Ea and the elemental and mercuric sulfide fractions for air-dried soils. However, for moist soils, Ea was negatively correlated with the water-soluble and acid-soluble fractions. Collectively, the combination of the Hg emission kinetics and Hg fraction measurement of different moist soils indicated that Hg emission was affected by both total Hg concentration and Hg fractions.

[Clinical observational study of Nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer].

Objective: To investigate the clinical efficacy and safety of Nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer. Methods: A total of 65 patients with locally advanced cervical cancer treated with Nimotuzumab combined with concurrent chemoradiotherapy in Tianjin Medical University Cancer Institute and Hospital were selected from January 2015 to November 2018. Intensity-modulated radiotherapy and intracavitary post-packaging were used for radiation therapy. Platinum and paclitaxel were used for chemotherapy. Nimotuzumab were 400 mg/week. The clinical efficacy, the changes of serum tumor markers and the occurrence of adverse events were observed for 2 years, and the evaluation was performed once for every 3 months. Results: Sixty-one cases could be evaluated by imaging during the follow-up. The best curative effect evaluation showed that complete remission (CR) was 43 (70.5%), partial remission (PR) was 9 (14.8%), stable disease (SD) was 6 (9.8%) and objective response rate (CR+PR) was 85.3%, disease control rate (CR+PR+SD) was 95.1%. Survival analysis showed that one-year overall survival rate was 93.9% and two-year overall survival rate was 79.6%. After 3 months of treatment, the serum tumor markers SCC, CA125, CEA, and HE4 were significantly lower than those before treatment (P<0.05). Safety assessments showed that the main adverse events were hematochezia, abdominal pain, diarrhea, fever and dizziness, and 37 cases of them were grades Ⅰ-Ⅱ. Conclusion: Nimotuzumab combined with concurrent chemoradiotherapy has a good clinical effect in the treatment of locally advanced cervical cancer, significantly reduces serum tumor marker levels after treatment, and is safe and tolerable in clinical use.

Platycodin D alleviates proliferation and extracellular matrix accumulation in TGF-beta1 induced pulmonary fibroblasts.

AIM: Platycodin D (PD), an oleanane kind of triterpenoid saponin, possesses various pharmacological activities. We aimed to investigate the effects of PD in pulmonary fibrosis. METHOD: MRC-5 cells were induced by transforming growth factor-beta1 (TGF-ß1) to simulate the pulmonary fibrosis in vitro. Cell viability was determined using a CCK-8 kit in the absence or presence of PD. Then, the expression of proliferation-related proteins was detected using immunofluorescence assay or western blot analysis. Moreover, the levels of inflammatory factors were examined. Subsequently, the ability of cell migration was evaluated using wound healing assay. Additionally, western blot analysis was employed to determine migration- and extracellular matrix accumulation (ECM)-related proteins expression. RESULTS: Results indicated that PD exposure significantly dose-dependently inhibited TGF-ß1 induced proliferation in MRC-5 cells. Additionally, the contents of inflammatory factors were notably inhibited with PD treatment. Furthermore, significant decrease in migration of TGF-ß1-stimulated MRC-5 cells was observed after PD intervention. Afterwards, PD remarkably suppressed the expression of alpha smooth muscle actin (α-SMA), collagen I (Col I), collagen III (Col III) and E-cadherin (E-cad). CONCLUSIONS: PD attenuated proliferation and ECM accumulation in TGF-ß1 induced lung fibroblasts, providing experimental support for the clinical application of PD in the treatment of pulmonary fibrosis (Fig. 6, Ref. 33).