[Clinical significance of lympho-vascular space invasion in different molecular subtypes of endometrial carcinoma].

Objective: To analyze the lympho-vascular space invasion (LVSI) in different molecular subtypes of the cancer genome atlas (TCGA) molecular subtypes of endometrial cancer (EC) and to evaluate the prognostic value of LVSI in EC patients with different molecular subtypes. Methods: A total of 258 patients diagnosed EC undergoing surgery in Peking University People's Hospital from January 2016 to June 2022 were analyzed retrospectively. Among 258 patients, 14 cases were classified as POLE-ultramutated subtype, 43 as high-microsatellite instability (MSI-H) subtype, 155 as copy-number low (CNL) subtype, and 46 as copy-number high (CNH) subtype. Fifty-four patients were positive for LVSI, while 203 tested negative. Results: (1) The incidence of LVSI was found to be highest in the CNH subtype (32.6%,15/46), followed by the MSI-H subtype (27.9%, 12/43), the CNL subtype (16.9%, 26/154), and the POLE-ultramutated subtype (1/14), with statistically significant differences (χ2=7.79, P=0.044). (2) Staging and deep myometrial invasion were higher in the LVSI positive group than those in the LVSI negative group (all P<0.05), except for the POLE-ultramutated subtype. The grade, lymph node metastasis, and the expression of nuclear antigen associated with cell proliferation (Ki-67) were significantly higher in LVSI positive patients than those in LVSI negative EC patients with both MSI-H and CNL subtypes (all P<0.05). In CNL subtypes patients, LVSI was also associated with age, histology subtype,and progesterone receptor (PR; all P<0.05). (3) Of the 257 EC patients, 25 cases recurred during the follow-up period, with a recurrence rate of 9.7% (25/257); among them, the recurrence rate of LVSI positive patients was 22.2% (12/54), which was significantly higher than those with LVSI negative (6.4%, 13/203; χ2=12.15, P<0.001). During the follow-up period, none of the 14 patients with POLE-ultramutated had recurrence; among CNL patients, the recurrence rate was 19.2% (5/26) in LVSI positive patients, which was significantly higher than that in LVSI negative ones (5.5%, 7/128; χ2=3.94, P=0.047); where as no difference were found in both MSI-H [recurrence rates in LVSI positive and negative patients were 2/12 and 9.7% (3/31), respectively] and CNH subtype [recurrence rates between LVSI positive and negative patients were 5/15 and 9.7% (3/31), respectively] EC patients (both P>0.05). After log-rank test, the 3-year recurrence free survival (RFS) rate were significantly lower in LVSI positive patients from CNL subtype and CNH subtype than those in LVSI negative patients (CNL: 80.8% vs 94.5%; CNH: 66.7% vs 90.3%; both P<0.05). (4) Lymph node metastasis (HR=6.93, 95%CI: 1.15-41.65; P=0.034) had a significant effect on the 3-year RFS rate of EC patients with MSI-H subtype. Multivariate analysis revealed that PR expression (HR=0.04, 95%CI: 0.01-0.14;P<0.001) was significantly associated with the 3-year RFS rate of CNL subtype patients. Conclusions: LVSI has the highest positivity rate in CNH subtype, followed by MSI-H subtype, CNL subtype, and the lowest positivity rate in POLE-ultramutated subtype. LVSI is significantly associated with poor prognosis in CNL subtype patients and may affect the prognosis of CNH subtype patients. However, LVSI is not an independent risk factor for recurrence across all four TCGA molecular subtypes.

Strategies for patients with recurrent nasopharyngeal carcinoma involved internal carotid artery who are intolerant to embolization.

BACKGROUND: The surgical treatment of recurrent nasopharyngeal carcinoma (rNPC) involving the internal carotid artery (ICA) is challenging, as the massive bleeding caused by intraoperative rupture of the ICA is life-threatening. We reported that ICA embolization is an effective pretreatment to avoid fatal bleeding, but some patients cannot tolerate the procedure. We used endovascular vascular protection (ICA stents), vascular sacrifice (bypass grafting) and extravascular vascular protection (transcervical external stent placement) of the ICA to provide alternative options for these patients. METHODOLOGYy: This study enrolled patients with rNPC adjacent to or invading the ICA who were unsuitable for ICA embolization from January 2015 to June 2020. ICA pretreatment combined with endoscopic nasopharyngectomy (ENPG) was performed for the 30 patients. We report the survival outcome and incidence of complications after ICA pretreatment. RESULTS: ICA pretreatment was performed for the 30 enrolled patients, among whom 8 underwent endoscopic-assisted transcervical protection of the parapharyngeal ICA combined with ENPG, 6 underwent bypass grafting, and 16 underwent ICA stent implantation followed by ENPG. After pretreatment, at a median follow-up of 43 months (range, 2-80 months), the 3-year locoregional overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 62.9%, 61.3%, 70.2%, and 71.4%, respectively. CONCLUSIONS: ICA pretreatment combined with salvage ENPG enables the feasible and effective resection of rNPC lesions involving the ICA in patients who cannot tolerate ICA embolization. Therefore, this treatment may be an effective method for improving outcomes. Multidisciplinary therapy is needed to reduce operation-related complications.

[Effects of preoperative diagnostic hysteroscopy on peritoneal cytology and prognosis in patients with non-endometrioid carcinoma].

Objective: To explore the effects of preoperative hysteroscopic guided biopsy and segmental diagnosis and curettage on the risk of abdominal dissemination and prognosis of non-endometrioid carcinoma. Methods: The clinical and pathological data of 97 patients who underwent surgical treatment and were pathologically confirmed as non-endometrioid carcinoma (including serous carcinoma, clear cell carcinoma, mixed adenocarcinoma, and undifferentiated carcinoma, etc.) from October 2008 to December 2021 in Peking University People's Hospital, were collected for retrospective analysis. According to preoperative diagnostic methods, they were divided into hysteroscopic group (n=44) and non-hysteroscopic group (n=53). The impact of hysteroscopy examination on peritoneal cytology and prognosis was analyzed. Results: (1) There were no statistical differences in age, body mass index, tumor size, pathological characteristics, and treatment methods between the hysteroscopic group and the non-hysteroscopic group (all P>0.05), but the proportion of stage Ⅰ-Ⅱ patients in the hysteroscopic group was significantly higher than that in the non-hysteroscopic group [68% (30/44) vs 47% (25/53); χ2=4.32, P=0.038]. (2) Among 97 patients, 25 (26%, 25/97) of them were cytologically positive for ascites. The hysteroscopic group had a lower positive rate of peritoneal cytology than that in the non-hysteroscopy group, which was significantly different [11% (5/44) vs 38% (20/53); χ2=8.74, P=0.003]. Stratification according to surgical and pathological stages showed that the positive rate of peritoneal cytology in the hysteroscopic group (3%, 1/30) was lower than that in the non-hysteroscopic group (12%, 3/25) in the 55 patients with stage Ⅰ-Ⅱ, and that in the hysteroscopic group (4/14) was also lower than that in the non-hysteroscopic group (61%, 17/28) in the 42 patients with stage Ⅲ-Ⅳ. There were no significant differences (all P>0.05). (3) The 5-year disease-free survival (DFS) rate of the hysteroscopic group and the non-hysteroscopic group were respectively 72.7% and 60.4%, and there was no significant difference between the two groups (P=0.186). After stratification according to staging, the 5-year DFS rate were respectively 90.0% and 72.0% (P=0.051) between the hysteroscopic and non-hysteroscopic groups of patients in stage Ⅰ-Ⅱ, and 35.7% and 50.0% (P=0.218) between the hysteroscopic and non-hysteroscopic groups of patients in stage Ⅲ-Ⅳ, in which there were not statistically significant differences. The 5-year overall survival (OS) rate were respectively 86.4% and 81.1% between the hysteroscopic group and the non-hysteroscopic group, with no significant difference between the two groups (P=0.388). The 5-year OS rate were respectively 93.3% and 96.0% in the hysteroscopic group and non-hysteroscopic group for patients with stage Ⅰ-Ⅱ(P=0.872), and 71.4% and 67.9% in the hysteroscopic group and non-hysteroscopic group in patients with stage Ⅲ-Ⅳ (P=0.999), with no statistical significance. Conclusions: Diagnostic hysteroscopy do not increase the rate of positive peritoneal cytology result at the time of surgery in this cohort, and no significant correlation between preoperative hysteroscopy examination and poor prognosis of non-endometrioid carcinoma is observed. Therefore, preoperative hysteroscopic guided biopsy and segmental diagnosis and curettage in non-endometrioid carcinoma maybe safe.

[Risk factor analysis of lymph node metastasis in endometrial carcinoma combined with molecular types].

Objective: To investigate the relationships between molecular types of the cancer genome atlas (TCGA) of patients with endometrial carcinoma (EC) and lymph node metastasis and other clinicopathological features. Methods: The clinical pathological information of 295 patients with EC who underwent initial inpatient surgical treatment and accepted the detection of the molecular types of TCGA with next-generation sequencing technology at Peking University People's Hospital were collected during April 2016 and May 2022. The TCGA molecular typing of EC was divided into four types: POLE-ultramutated (15 cases), high microsatellite instability (MSI-H; 50 cases), copy-number low (CNL; 175 cases), and copy-number high (CNH; 55 cases). The differences of clinical pathological features among different molecular types and the risk factors of lymph node metastasis were analyzed retrospectively. Results: Among 295 patients with EC, the average age was (56.9±0.6) years. (1) There was a statistically significant difference in lymph node metastasis (0, 8.0%, 10.3% and 25.5%) among the four molecular types (χ2=12.524, P=0.006). There were significant differences in age, stage, pathological type, grade (only endometrioid carcinoma), myometrium invasion, lymphatic vascular space infiltration, and estrogen receptor among the EC patients of four molecular types (all P<0.05). Among them, while in the patients with CNH type, the pathological grade was G3, the pathological type was non-endometrioid carcinoma, and the proportion of myographic infiltration depth ≥1/2 were higher (all P<0.05). (2) Univariate analysis suggested that pathological type, grade, myometrium infiltration depth, cervical interstitial infiltration, lymphatic vascular space infiltration, and progesterone receptor were all factors which significantly influence lymph node metastasis (all P<0.01); multivariate analysis suggested that the lymphatic vascular space infiltration was an independent risk factor for lymph node metastasis (OR=5.884, 95%CI: 1.633-21.211; P=0.007). (3) The factors related to lymph node metastasis were different in patients with different molecular types. In the patients with MSI-H, the non-endometrioid carcinoma of pathological type was independent risk factor for lymph node metastasis (OR=29.010, 95%CI: 2.067-407.173; P=0.012). In the patients with CNL, myometrium infiltration depth≥1/2 (OR=4.995, 95%CI: 1.225-20.376; P=0.025), lymphatic vascular space infiltration (OR=14.577, 95%CI: 3.603-58.968; P<0.001) were the independent risk factors for lymph node metastasis. While in the CNH type patients pathological type of non-endometrioid carcinoma (OR=7.451, 95%CI: 1.127-49.281; P=0.037), cervical interstitial infiltration (OR=22.938, 95%CI: 1.207-436.012; P=0.037), lymphatic vascular space infiltration (OR=9.404, 95%CI: 1.609-54.969; P=0.013), were the independent risk factors for lymph node metastasis. Conclusions: POLE-ultramutated EC patients have the lowest risk of lymph node metastasis, and CNH patients have the highest risk of lymph node metastasis. The risk factors of lymph node metastasis of different molecular types are different. According to preoperative pathological and imaging data, lymph node metastasis is more likely to occur in patients with non-endometrioid carcinoma in MSI-H and CNH type patients, and lymph node metastasis is more likely to occur in patients with myometrium infiltration depth ≥1/2 in CNL type patients.

[Prognosis analysis of radical or modified radical hysterectomy and simple hysterectomy in patients with stage â ¡ endometrial cancer].

Objective: To compare the prognosis and perioperative situation of patients with stage Ⅱ endometrial cancer (EC) between radical hysterectomy/modified radical hysterectomy (RH/mRH) and simple hysterectomy (SH). Methods: A total of 47 patients diagnosed EC with stage Ⅱ [International Federation of Gynecology and Obstetrics (FIGO) 2009] by postoperative pathology, from January 2006 to January 2021 in Peking University People's Hospital, were analyzed retrospectively. The patients were (54.4±10.7) years old, and the median follow-up time was 65 months (ranged 9-138 months). They were divided into RH/mRH group (n=14) and SH group (n=33) according to the scope of operation. Then the prognosis of patients between the groups were compared, and the independent prognostic factors of stage Ⅱ EC were explored. Results: (1) The proportions of patients with hypertension in RH/mRH group and SH group were 2/14 and 45% (15/33), the amounts of intraoperative blood loss were (702±392) and (438±298) ml, and the incidence of postoperative complications were 7/14 and 15% (5/33), respectively. There were significant differences (all P<0.05). (2) The median follow-up time of RH/mRH group and SH group were 72 vs 62 months, respectively (P=0.515). According to Kaplan-Meier analysis and log-rank method, the results showed that there were no significant difference in 5-year progression-free survival (PFS) rate (94.3% vs 84.0%; P=0.501), and 5-year overall survival rate (92.3% vs 92.9%; P=0.957) between the two groups. Cox survival analysis indicated that age, pathological type, serum cancer antigen 125 (CA125), and estrogen receptor (ER) status were associated with 5-year PFS rate (all P<0.05). But the scope of hysterectomy (RH/mRH and SH) did not affect the 5-year PFS rate of stage Ⅱ EC patients (P=0.508). And level of serum CA125 and ER status were independent prognostic factors for 5-year PFS rate (all P<0.05). Conclusions: This study could not find any survival benefit from RH/mRH for stage Ⅱ EC, but increases the incidence of postoperative complications. Therefore, the necessity of extending the scope of hysterectomy is questionable.

Stent pretreatment for internal carotid artery exposed to necrotic lesions in nasopharyngeal carcinoma.

BACKGROUND: Post radiation nasopharyngeal necrosis (PRNN) invading the internal carotid artery (ICA) contributes to the death of 69.2-72.7% of PRNN patients. ICA occlusion is an effective treatment to avoid fatal bleeding, while some patients are intolerant. We present a novel method that allows for these patients without interrupting blood flow through the ICA. METHODOLOGY: This study enrolled patients with PRNN-invaded ICA who were not suitable for ICA occlusion from April 2020 to November 2022. ICA stent pretreatment was performed in the 36 patients and followed the endoscopic nasopharyngectomy (ENPG) or conservative treatment for PRNN. We report the survival outcome and incidence of complications after stent implantation and compare the survival outcomes of ENPG and conservative treatment for PRNN followed by stent implantation. RESULTS: ICA stent pretreatment was performed in the 36 enrolled patients, among which 14 underwent ENPG, and 22 received conservative treatment. 27.8% patients died after a median follow-up of 15 months. The Kaplan-Meier estimates of overall survival were higher in the ENPG group than in the conservative treatment group. Karnofsky performance status (KPS) was significantly higher in the ENPG group than in the non-ENPG group. CONCLUSIONS: The innovative application of ICA stents is a promising treatment to improve outcomes in patients with PRNN invading the ICA who are unsuitable for ICA embolization, especially when followed by endoscopic surgery. However, methods to avoid postoperative cerebral ischemia and nasopharyngeal hemorrhage still require further study.

[Synchronous primary bilateral macronodular adrenal hyperplasia with renal cell carcinoma: a case series of three patients].

Three cases of synchronous primary bilateral macronodular adrenal hyperplasia(PBMAH) and renal cell carcinoma (RCC) in the Department of Urology of Peking Union Medical College Hospital were retrospectively reviewed. The clinical features, imaging features, treatment methods and pathological features of these patients were analyzed. It was found that the genetic relationship between synchronous PBMAH and RCC needs further research. And RCC is easy to be misdiagnosed. We should pay high attention to imaging features to find out whether there are lesions in bilateral kidneys when we deal with bilateral adrenal lesions. Laparoscopic approach is recommended for PBMAH and RCC. Total or partial nephrectomy should be performed according the tumor size and location of the renal mass. Patients with PBMAH should be closely followed up after bilateral adrenalectomy to avoid delay in diagnosis or treatment of RCC.

[Data analysis of application and funding of ophthalmology projects funded by National Natural Science Foundation of China from 2010 to 2021].

Objective: To review the application for funding of ophthalmologic projects from the National Natural Science Foundation of China (NSFC) and the current research progress, and to provide reference for the promotion of basic eye research in China. Methods: The NSFC application and funding information of ophthalmology-related projects from 2010 to 2021 were collected as a database for further analysis. The main categories of the analysis included the number of application and funding, the funding ratio, the research directions and the funded organizations. Results: During the 12 years, 13 267 applications were received in the field of ophthalmology, with an increase of 157.21% (1 025/652) in 2021 compared with 2010, and the number of applications for the Youth Foundation grew significantly. There were 2 221 funded projects, with an increase of 81.51% (97/119) in 2021 compared with 2010. After 2017, the number of funded projects was basically around 200 per year, with a funding rate of 16.74%(2 221/13 267). The funding amount was 1 026.9 million yuan in total, with an average of 462 400 yuan. Sun Yat-sen University (1 060 applied and 265 funded projects), Fudan University (759 applied and 186 funded projects), Shanghai Jiaotong University (820 applied and 178 funded projects), Wenzhou Medical University (625 applied and 113 funded projects) and Capital Medical University (538 applied and 95 funded projects) were the top five institutions in terms of the number of application and funding. Conclusions: From 2010 to 2021, the application number of ophthalmology projects increased rapidly, while the number of funded projects increased slowly, and the funding ratio decreased year by year. With the support of NSFC, the basic research of ophthalmology in China has made great progress. However, we still need to find and solve problems to promote the sustainable advance of ophthalmology. (This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on January 21, 2022).

[Establishment of human colon cancer transplantation tumor model in normal immune mice].

Objective: Establishment of a new model of human primary colon cancer transplantation tumor in normal immune mice and to provide a reliable experimental animal model for studying the pathogenesis of colon cancer under normal immunity. Methods: Human colon cancer cells come from colon cancer patients who underwent surgery in the Affiliated Hospital of Jining Medical College in 2017. The mice in the cell control group were inoculated with phosphate buffered solution (PBS) containing colon cancer cells, the microcarrier control group was inoculated with PBS containing microcarrier 6, and the cell-microcarrier complex group was inoculated with the PBS containing colon cancer cell-microcarrier complex. The cells of each group were inoculated under the skin of the right axilla of mice by subcutaneous injection, and the time, size, tumor formation rate and pathological changes under microscope were recorded. The transplanted tumor tissue was immunohistochemically stained with the EnVisiion two-step method, and the tumor formation rate of the transplanted tumor was judged according to the proportion of positive cells in the visual field. The polymerase chain reaction (PCR) method was used to detect the expression of human-specific Alu sequence in mice tumor tissue. Results: After inoculation with tumor cells, the mice in the cell control group and the microcarrier control group did not die and did not form tumors; the mice in the cell-microcarrier complex group had palpable subcutaneous tumors in the right axillary subcutaneously on the 5th to 7th days after inoculation, and tumor formation rate is 67% (10/15), and the tumor volume can reach about 500 mm(3) 2 to 3 weeks after vaccination. The immunohistochemistry results showed that CK20, CDX-2 and carcinoembryonic antigen were all positively expressed. The PCR results showed that the expression of human-specific Alu sequence can be detected in the transplanted tumor tissue of tumor-bearing mice. Conclusion: Human primary colon cancer cells used microcarrier 6 as a carrier to form tumors in normal immunized mice, and successfully established a new model of human colon cancer transplantation tumor in normal immune mice.

[Analysis of early recurrence within 6 months in patients of esophageal squamous cell carcinoma after neoadjuvant therapy followed by surgery].

Objectives: To examine the prognosis factors of recurrence of esophageal carcinoma within 6 months after neoadjuvant therapy followd by surgery. Methods: The clinical data of 187 patients with esophageal squamous cell carcinoma who underwent neoadjuvant therapy followed by curative esophagectomy between January 2018 and April 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital were analyzed retrospectively. There were 160 males and 27 females, aging (63.0±7.1) years (range:43 to 76 years). The t test, χ2 test and rank-sum test were used for univariate analysis of the prognosis factors for recurrence within 6 months postoperative, while the Logistic regression was used for multivariate analysis. Results: There were 30 patients (16.0%) developed recurrence within 6 months after operation, including local recurrence in 1 case, regional recurrence in 11 cases, hematogenous recurrence in 13 cases, and combined recurrence in 5 cases. Univariate analysis suggested that there was a significant difference in T staging of tumor before neoadjuvant therapy (cT), tumor regression grade, circumferential resection margin, pathological T stage (ypT) and pathological N stage (ypN) between the recurrence patients and non-recurrence patients (all P<0.05). Logistic regression analysis suggested that the cT3-4 (OR=2.701, 95%CI: 1.161 to 6.329, P=0.021) and ypN(+)(OR=1.654, 95%CI: 1.045 to 2.591, P=0.032) were the independent prognosis factors for recurrence within 6 months. Conclusion: The combination of neoadjuvant therapy and surgery is not effective in reducing early postoperative recurrence in patients who have invaded the epineurium before treatment, and still have positive lymph nodes after neoadjuvant therapy.

[Preliminary results of Chinese magnetic sphincter augmentation in treating gastroesophageal reflux disease].

Objective: To examine the preliminary clinical efficacy of Chinese magnetic sphincter augmentation (MSA) in the treatment of gastroesophageal reflux disease (GERD). Methods: According to the enrollment criteria for the MSA developed by ShengJieKang Co. and Shanghai Chest Hospital (SS-MSA) clinical trial, a total of 19 GERD patients were treated with SS-MSA from August 2018 to January 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University. The majority of registered cases were male patients with age of (32.2±7.3) years (range: 22 to 50 years), height of (170.7±6.2) cm (range: 160 to 179 cm) and weight of (65.2±10.3) kg (range: 47.5 to 90.0 kg). SS-MSA was implanted via laparoscopy. The major evaluation indexs of postoperative efficacy were the total time of acid exposure within 24 hours and the total number of reflux. Secondary efficacy indicators included: (1) evaluation of the average daily dose of proton pump inhibitor medications; (2) the score of GERD health related quality of life questionnaire (GERD-Q) before and after MSA implantation. Paired design t-test was used to evaluate the efficacy of the SS-MSA. Results: A total of 19 patients underwent SS-MSA surgery successfully. The history of the GERD were 19 (54) months (M(Q(R))). The operation time was 63 (22) minutes and the in-hospital stay was 3 (2) days. No obvious surgical complications occurred. Postoperative adverse events included 14 cases with mild to moderate dysphagia exited after surgery, gradually eased within 1 to 3 months, 1 case with the removal of the device after 1 month of severe swallowing difficulties, 1 case of diarrhea. No corrosion, perforation, displacement occurred. The GERD-Q score (11.0(4.5) vs. 6(1.0), t=4.274, P=0.013), 24-hour acid exposure time (6.2(4.8)% vs. 0.1(0.9)%, t=5.814, P=0.004), and Demeester score (23.72(16.20) vs. 0.96(3.10), t=6.678, P=0.003) were significantly decreased 1 year after surgery(n=5). Proton pump inhibitor reuse rates were 6/18, 5/15, 3/10, and 1/5 in 1, 3, 6 and 12 months after the operation, respectively. Conclusions: SS-MSA implantation is feasible and safe with short hospital stay and rare perioperative complications. The preliminary results is good after 1 year follow-up. It could be expected to be an ideal substitutive for future GERD treatment.

[Intrauterine balloon tamponade combined with temporary abdominal aortic balloon occlusion in the management of women with placenta accreta spectrum:a randomized controlled trial].

Objective: To access the effectiveness and safety of the intrauterine balloon tamponade verse gauze packing combined with temporary abdominal aortic balloon occlusion in the management of placenta accreta spectrum (PAS). Methods: This was an open-label, randomized controlled trial conducted in Nanjing Drum Tower Hospital. The patients suspected with PAS for uterine preservation surgery under the multidisciplinary team care were recruited between Aug 2015 and Jan 2018. When bleeding could not be achieved after fetus delivered, and a temporary abdominal aortic balloon occlusion and the compression sutures as needed, the women were randomly allocated 1∶1 into balloon tamponade (n=81) or gauze packing (n=80) group. The primary outcome was successful bleeding arrests by avoiding second line surgeries. The secondary outcomes included the volume of blood loss during and after cesarean section, the rate of PPH, incidence and amount of blood transfusion, hysterectomy, postpartum pain, ICU admission, need for re-laparotomy, and the length of hospital stay, readmission, and interventional radiology complications. Results: All the women [100% (81/81)] in the balloon group were obtained hemostasis without further intervention, significantly higher than 88% (70/80) in the gauze group (P=0.001). Before uterine tamponade, blood loss were 820 ml (620-1 230) ml and 850 ml (605-1 442) ml, while placenta bed were sutured in 96%（78/81, 77/80） respectively (P>0.05).The proportion of blood loss≥1 000 ml was higher in the gauze group than that in the balloon group (P=0.006). Maternal adverse events involving total blood loss, puerperal morbidity and postpartum pain occurred more frequently in the gauze group (P<0.05). The following outcome showed no statistically significant difference between the two groups: the vascular occlusion time, the dose of radiation, and interventional radiology complication (P>0.05). The median volume infused into the lower and upper balloons is 70 ml (50-100 ml) and 180 ml (100-240 ml). Conclusions: Incrauterine balloon tamponade is as effective as gauze packing in hemostasis following the placenta delivery in PAS. Compared with gauze packing, the uterine balloon tamponade is more effective.

[Anti-PD-1 therapy in advanced malignant liver tumor-induced type-1 diabetes mellitus: a case report].

Immune checkpoint inhibitor (ICI) has been emerged as a major breakthrough in tumor immunotherapy, but its unique mechanism of action has also led to a number of immune-related adverse events (irAE). Type 1 diabetes mellitus (T1DM) is one of the rarest irAEs. This paper reports a case of advanced malignant liver tumor-induced T1DM who received second-line anti-PD-1 therapy and showed initial symptoms of hyperosmolar coma and hyperglycemia. In addition, the relevant literature at home and abroad was collected and reviewed, and the clinical characteristics of T1DM induced by anti-PD-1 therapy were summarized with a view to achieve early detection, diagnosis and treatment.

[Evaluation and embolization strategy by ASITN/SIR grade for injured internal carotid artery of nasopharyngeal carcinoma].

Objective: To study the strategy of endovascular treatment for patients with the risks of internal carotid artery (ICA) rupture and bleeding during the treatment of nasopharyngeal carcinoma (NPC) based on American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grade of collateral circulation. Methods: A total of 56 patients (45 males and 11 females, aged from 28 to 76 years old) diagnosed with nasopharyngeal carcinoma and admitted to the Department of Neurosurgery, the Third Affiliated Hospital of Southern Medical University from July 2018 to January 2020 were retrospectively analyzed. There were 15 cases of ASITN/SIR grade 4, 24 cases of ASITN/SIR grade 3, 5 cases of ASITN/SIR grade 2, 5 cases of ASITN/SIR grade 1, and 7 cases of ASITN/SIR grade 0. The events of stroke and death were analyzed statistically. Results: ALL patients with ASITN/SIR grade 4 or 3 and some of patients with ASITN/SIR grades 2-0 passed balloon occlusion test and electrophysiological monitoring. ICA pseudoaneurysm was found in 35 patients, and one-stage ICA embolization was performed in 29 patients after evaluation. Among them, 8 cases of ASITN/SIR grade 4 and 10 cases of ASITN/SIR grade 3 with obvious posterior circulation compensation obtained successful one-stage ICA embolization without cerebral ischemia; cerebral ischemic events occurred in 5 (55.6%) of 9 patients with ASITN/SIR grade 3 and in 1(50.0%) of 2 patients with ASITN/SIR grade 2. The total incidence of ischemic events was 20.7% (6/29) and 1 case was disabled (1/29, 3.4%). Among patients with ASITN/SIR 3, there were statistically significant differences in stroke event rate between patients with obvious posterior circulation compensation and patients with slight or without posterior circulation compensation (0/10 vs. 5/9, χ(2)=4.95, P=0.026). Follow-up time was 10.1±7.8 months, and 46 patients were survival (46/56, 82.1%) and 10 patients died (10/56, 17.9%) with a mean survival time of 2.6±1.4 months. Conclusions: For NPC patients with ICA invasion, ASITN/SIR based on DSA can simplify the assessment process of cerebral blood flow compensation. ICA can be embolized directly in patients with ASITN/SIR 4 or 3 with obvious posterior communicating compensation.

The crosstalk between IGF-1R and ER-α in the proliferation and anti-inflammation of nucleus pulposus cells.

OBJECTIVE: Insulin-like growth factors-1 receptor (IGF-1R) and estrogen receptor (ER) are reported to co-express and engage in crosstalk involving in the synergistic effect of various aspects. It is unknown whether this crosstalk exists in the nucleus pulposus (NP) cells. We aimed to investigate the interaction between IGF-1R and ER-α in regulating NP cell proliferation and inflammation response under IGF-1 stimulation. PATIENTS AND METHODS: We analyzed the IGF-1, IGF-1R, and ER-α in different degenerated degree human NP tissues. NP cells were cultured with IGF-1 protein with or without the inhibitor of IGF-1R or ER-α to investigate their effects on the proliferation and inflammation response. In addition, we also upregulated the IFG-1R and ER-α expression by plasmid transfection to investigate the impact on each other. The content of IGF-1, IFG-1R, and ER-α was analyzed by enzyme-linked immunosorbent assay (ELISA). The proliferative cell rate was determined by flow cytometry. Additionally, intracellular collagen-II, p16, PCNA, IL-1ß, IL-6, TNF-α, and MMP-13 expression were also detected. RESULTS: We found IGF-1, IFG-1R, and ER-α content were decreased in higher degenerated NP tissues. IGF-1 protein treatment upregulated the IFG-1R and ER-α expression and promoted NP cell proliferation, collagen-II, and PCNA expression. However, the suppression of IGF-1R (or ER-α) weakened the IGF-1 induced collagen-II expression, proliferation, and anti-inflammation effects on NP cells, decreased ER-α (or IGF-1R) expression, and partly reversed the protective effect of NP cells caused by IGF-1 Similarly, the upregulation of one of IGF-1R and ER-α may increase the other as well. CONCLUSIONS: There is an interaction between IGF-1R and ER-α acts synergistically to promote the proliferation and suppress inflammation in NP cells.

[Application and funding status of otorhinolaryngology head and neck surgery research projects funded by National Natural Science Foundation of China from 2009 to 2019].

Objective: Based on the application and funding of Otorhinolaryngology Head and Neck Surgery (H13) funded by the Nature Science Foundation of China (NSFC), we analyzed the basic research status of the field of Otorhinolaryngology Head and Neck Surgery, and provided the references for developing the discipline development plan, optimizing the discipline strategic layout and promoting the discipline progress. Method: The data of both applied and funded grants of Otorhinolaryngology Head and Neck Surgery in NSFC from 2009 to 2019 were collected for further analysis. Results: From 2009 to 2019, H13 received 5 103 applications, accounting for 1.00% of the total number of applications in the department of health science, and 922 applications were funded (mainly from the General Projects and the Youth Science Fund Projects), with a funding rate of 18.07% and a funding amount of 445.509 million yuan, accounting for 1.02% of the total funding amount of the department of health science. Among the seven sub-categories of H13, H1304 (Hearing abnormal and balance disorders) received 1 845 applications, and 352 were funded. H1301 (Disease of smell, nose and anterior skull base) received 1 217 applications, and 248 were founded, H1303 (Ear and lateral skull base disease) and H1305 (Otorhinolaryngology and developmental related diseases) received 498 and 488 applications,and 83 and 112 were founded respectively. The National Science Fund for Distinguished Young Scholars received 33 applications, and 5 were founded, with a funding rate of 15.15%. Clinicians accounted for 81% of the General Projects principals, and researchers and technicians accounted for 19%. Clinicians accounted for 72% of the Youth Science Fund Projects principals, and researchers and technicians accounted for 24%. Conclusion: The basic research of Otorhinolaryngology Head and Neck Surgery in China has some shortcomings, such as small volume, uneven development of various disciplines, less leading academic leaders, less training of young leading talents, less major projects, more clinicians instead of researchers engaged in the basic scientific research.

LncRNA Bmncr alleviates the progression of osteoporosis by inhibiting RANML-induced osteoclast differentiation.

OBJECTIVE: To elucidate whether long non-coding RNA (lncRNA) Bmncr could inhibit RANML-induced osteoclast differentiation, thus alleviating the progression of osteoporosis. MATERIALS AND METHODS: Expression level of lncRNA Bmncr at different stages of osteoclast differentiation was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). After Bmncr overexpression or knockdown in RAW 264.7 cells, expression levels of osteoclast-related genes were detected. Bone marrow mesenchymal stem cells (BMMs) isolated from rats undergoing ovariectomy (OVX) were induced with RANKL (50 ng/mL) and M-CSF (50 ng/mL) for 120 h. TRAP staining was conducted to count the number of TRAP-positive osteoclasts containing more than three nuclei. Bone resorption area of bone fragments was quantitatively analyzed. Osteoporosis model in mice was established. Mice were subjected to MicroCT analyses for recording BMD and BV/TV. The expression level of lncRNA Bmncr in the marrow and spleen of osteoporosis mice was examined. RESULTS: LncRNA Bmncr was lowly expressed in the marrow and spleen of osteoporosis mice. Besides, Bmncr expression gradually downregulated during RANKL-induced in vitro osteoclast differentiation, reaching the lowest level at 72 h. The overexpression of Bmncr reduced the amount of osteoclasts, inhibited bone resorption capacity, and downregulated expression levels of Atp6v0d2, Acp5, Ctr, and Mmp9. Conversely, Bmncr knockdown obtained the opposite trends. CONCLUSIONS: LncRNA Bmncr inhibits RANKL-induced osteoclast differentiation, thus alleviating the progression of osteoporosis.

[The inhibition of 18ß-sodium glycyrrhetinic acid on thymic stromal lymphopoietin expression in the nasal mucosa of allergic rhinitis rats].

Objective: To explore the effect of 18ß-sodium glycyrrhetinic acid on thymic stromal lymphopoietin (TSLP) in nasal mucosa of allergic rhinitis (AR) rats. Methods: One hundred Wistar rats,half male and half female,were randomly divided into 5 groups by random number table method: control group, AR model group,budesonide group,18ß-sodium glycyrrhetinic acid at dose of 20 mg/kg and 40 mg/kg groups, with 20 rats in each group. AR animal models were established by ovalbumin (OVA) sensitization in the other four experimental groups. After successful modeling, budesonide and 18ß-sodium glycyrrhetinic acid were given in each group,and the detection time points were 2 weeks and 4 weeks. The distribution of TSLP in rat nasal mucosa was detected by immunohistochemistry,and the expression of TSLP in rat nasal mucosa was determined by Western blot at the protein level. The expression of TSLP-mRNA in rat nasal mucosa was detected and compared by real-time fluorescence quantitative PCR (RT-PCR) at mRNA level. The concentrations of IL-4 and OVA-sIgE in rat serum were measured and compared by ELISA. One-way analysis of variance and the least significant difference method were used for the comparison among groups, LSD t test was used for the comparison between the two groups,and the difference was statistically significant (P<0.05). Results: Immunohistochemistry confirmed existence of TSLP in rat nasal mucosa, especially in epithelial cells,endothelial cells and epithelial cilia. Western blot and RT-PCR suggested that the expression of TSLP and TSLP-mRNA in nasal mucosa of AR model group was significantly higher than that of control group (2 weeks TSLP: 1.795 9±0.131 4 vs 0.990 5±0.164 2, 4 weeks TSLP: 1.809 7±0.253 4 vs 0.870 3±0.124 4; 2 weeks TSLP-mRNA:4.582 9±0.697 7 vs 1.108 7±0.081 1, 4 weeks TSLP-mRNA:4.814 4±0.662 8 vs 1.001 0±0.155 3; all P<0.05). After 2 weeks and 4 weeks of drug intervention,the expression of TSLP and TSLP-mRNA was inhibited in nasal mucosa of budesonide group,18ß-sodium sodium glycyrrhetinic acid at dose of 20 mg/kg and 40 mg/kg group,which was significantly different from that of AR model group (2 weeks TSLP: (0.897 8±0.081 8)/(1.072 1±0.113 6)/(1.396 6±0.133 9) vs 1.795 9±0.131 4; 4 weeks TSLP: (1.191 0±0.161 3)/(1.141 0±0.152 3)/(1.200 5±0.189 6) vs 1.809 7±0.253 4; 2 weeks TSLP-mRNA: (1.175 6±0.100 9)/(1.254 4±0.078 2)/(2.037 2±0.559 2) vs 4.582 9±0.697 7; 4 weeks TSLP-mRNA: (1.158 3±0.104 3)/(1.224 0±0.034 0)/(1.275 2±0.099 6) vs 4.814 4±0.662 8; all P<0.05), and not significantly different from control group. With the inhibition of TSLP, the concentrations of IL-4 and OVA-sIgE in rat serum were also decreased. Conclusion: 18ß-sodium glycyrrhetinic acid has obvious inhibitory effect on TSLP in nasal mucosa of AR rats, which can control Th2 type immune inflammatory reaction.