Hypoxia inducible factors(HIFs)are core molecules that enable the body to adapt to hypoxia environments.By sensing changes in intracellular oxygen pressure,HIFs regulate gene expression related to hypoxia adaptation,thereby enhancing the body's hypoxia tolerance at cellular,tissue and organ levels.On the other hand,HIFs promote the generation of red blood cells,angiogenesis,and regulate the body's energy metabolism,thereby improving its hypoxia tolerance.The enhancement of hypoxia tolerance is of great significance for the prevention and treatment of hypoxia-related diseases,upgrading of athletes'performance,enhancement of workers'efficiency at high-altitudes,and the improvement of individu-als'quality of life.This article reviews the relationships between HIFs and hypoxia tolerance as well as related mechanisms in order to provide strategies for enhancing hypoxia tolerance in the body.

Objective:To explore the effect of the isolated organ laparoscopic simulation training teaching mode in laparoscopic partial nephrectomy training.Methods:A 39-hour in vitro organ laparoscopic simulation training for 12 urologists who had previously participated in laparoscopic basic technique training but had not independently completed laparoscopic partial nephrectomy in Peking Union Medical College Hospital. The training was conducted twice a week for 3 months from April to June 2022. Five modules, namely ultrasonic knife separation training, ultrasonic knife cutting training, vascularization training, blunt separation training, and partial nephrectomy and wound closure training, were used to provide targeted training for the decomposition of laparoscopic partial nephrectomy, and each training item was assessed and scored according to the scoring rules. At the same time, a questionnaire was used to find out the level of confidence of the 12 physicians in completing the operation and each step in the procedure, so as to assess the changes in the operational skills and psychological quality of the physicians before and after training using paired t-tests or Wilcoxon paired rank sum tests. Results:After the training, the assessment scores of operations in all surgeons were significantly improved. The training scores of ultrasonic knife separation training, ultrasonic knife cutting training, blood vessel nudity training, blunt separation training, and partial nephrectomy and traumatic suture improved from (8.5±0.3), (6.9±0.3), (4.2±0.4), (6.6±0.4), and (5.6±0.7) to (9.8±0.2), (9.6±0.3), (9.3±0.2), (9.4±0.3), and (9.8±0.2), respectively( P<0.05). The average operation time for the partial renal excision and traumatic suture training improved from (47.5±5.8) minutes to (21.6±5.1) minutes( t=18.72, P<0.001). At the same time, self-confidence in completing the operation was also significantly improved from 2(1, 3) before the training to 4(4, 4) after the training ( Z=-3.002, P =0.003). Conclusions:After laparoscopic simulation training with isolated organs, physicians with no previous experience in partial nephrectomy can become proficient in all steps of the procedure, complete the resection of the renal tumor and suturing of the wound within 30 minutes, and gain confidence in the operation of all steps of partial nephrectomy.

Objective:Investigating the efficacy of unilateral adrenalectomy in treatment for primary pigmented nodular adrenocortical disease (PPNAD).Methods:Clinical data of 26 patients with PPNAD treated in our hospital from January 2013 to June 2023 was retrospectively analyzed.There were 11 males and 15 females, with an average age of (19.4±4.7) years. 25 cases presented with typical Cushing's syndrome, and 16 cases were diagnosed with Carney's syndrome. PRKAR1A gene mutation detected in 8 out of 10 cases. CT showed multiple small nodules on bilateral adrenal glands in 14 cases, unilateral small nodules or mild thickening with normal contralateral glands in 8 cases, and no obvious abnormalities in 4 cases. All patients showed autonomous oversecretion of cortisol by endocrine laboratory tests, with a median 24 h-UFC of 408.35 (334.28, 800.78) μg/24 h and decreased level of adrenocorticotropic hormone. All 26 patients underwent laparoscopic unilateral adrenalectomy, with left side adrenalectomy in 8 cases and right side adrenalectomy in 18 cases.Results:The average surgical duration was (85.2±28.7) minutes, with intraoperative blood loss <50 ml in all cases. The median time to drainage tube removal post-operation was 3 (2, 3) days. One patient developed a postoperative pulmonary infection, and 3 patients required postoperative hormone replacement therapy. The median follow-up duration was 64 (31.5, 103.8) months, and all patients showed alleviation of Cushing syndrome clinical manifestations after operations. 19 patients (73.1%) had their 24 h-UFC levels normalized to a median of 42.0 (22.4, 58.3) μg/24 h within 8.5 (5, 46) days post-surgery. 7 patients (26.9%) did not achieve normal 24 h-UFC levels, yet experienced an average reduction of (73.2±10.4)%. 13 patients (50.0%) did not experience recurrence, with a median follow-up of 51 (7, 89.5) months, including two cases without recurrence at 10 years post-surgery. 13 patients showed recurrent increase in postoperative cortisol levels, with a median of 225.6 (188.9, 397.2) μg/24 h. The median time to increased 24 h-UFC post-surgery was 27 (13.5, 50.5) months, with the longest duration reaching 104 months. Among these, 9 cases exhibited clinical signs and symptoms of recurrence, while 4 cases did not. Of the 13 patients with recurrence, 9 underwent contralateral adrenalectomy or subtotal resection, while 4 were observed with follow-up.Conclusions:Unilateral adrenalectomy could be a surgical treatment option for PPNAD. Despite the recurrence in some patients postoperatively, unilateral adrenalectomy could effectively and rapidly reduce cortisol levels in PPNAD patients and alleviate the clinical manifestations of Cushing syndrome.

Objective:To study the efficacy and safety of early abdominal puncture drainage (APD) in severe acute pancreatitis (SAP).Methods:A retrospective study was conducted on 189 patients with SAP who were managed at the Department of Intensive Medicine of the Second Affiliated Hospital of Anhui Medical University from January 2013 to May 2020. According to whether ultrasound-guided APD was performed within one week after admission to ICU, these patients were divided into 2 groups: patients treated with APD (the APD group) and patients treated without APD (the non-APD group). Clinical data, including the acute physiological and chronic health status (APACHE) Ⅱ score, modified Marshall score, sequential organ failure evaluation (SOFA) score, and prognostic indicators including the retroperitoneal percutaneous drainage (PCD) rate and length of hospital stay, were compared between the two groups before and 1 week after surgery.Results:Of the 189 SAP patients in this study, there were 110 males and 79 females, aged (52.5±17.4) years old. On admission to ICU, the blood amylase, C-reactive protein, procalcalonin, interleukin-6, APACHE II score, modified Marshall score and SOFA score in the APD group were significantly higher than those in the non-APD group. After 1 week of treatment, most clinical indicators in the 2 groups were significantly improved, and there were no significant differences between these indicators (all P>0.05). There were no significant differences in the abdominal infection, retroperitoneal PCD and mortality rates between the APD group and the non-APD group ( P>0.05). The length of hospital stay [29 (18, 45) vs 21 (15, 32) d] and ICU stay [5 (3, 11) vs. 7 (5, 17) d] in the APD group were significantly higher than those in the non-APD group ( P<0.05). Conclusion:For patients with SAP with peritoneal effusion, early APD effectively improved the condition and prognosis without increasing the peritoneal infection and mortality rates.

Objective:To compare the outcomes of low-dose-rate prostate brachytherapy (BT) and radical prostatectomy (RP) in patients with T 1c-T 3a prostate cancer. Methods:A group of 745 patients with T 1c-T 3a prostate cancer between January 2010 and August 2017 at Peking Union Medical College Hospital were identified. The records of these patients, who were followed up for a minimum of 2 years, were reviewed. 384 cases received BT. Their characters included age(72.1±6.6), tPSA (12.4±6.1) ng/ml, prostate volume (33.6±13.8) ml, Gleason grade group (2.0±1.2). In this group, T 1c-T 2a stage was diagnosed in 189 cases, T 2b-T 2c stage in 182 cases and T 3a stage in 13 cases.361 cases received RP. Their characters included age(65.7±6.2), tPSA(12.6±6.4) ng/ml, prostate volume (37.2±17.8) ml, Gleason grade group (1.9±1.2). In this group, T 1c-T 2a stage was diagnosed in 177 cases, T 2b-T 2c stage in 170 cases and T 3a stage in 14 cases.The log-rank test compared survival rates between the two modalities, and Cox regression identified factors associated with bRFS. Results:Median follow-up was 60 months. Kaplan-Meier analysis did not show any statistically significant differences in terms of cRFS( P=0.321), cancer specific survival (CSS, P=0.643) and overall survival (OS, P=0.565) rate between the two groups. BT was associated with improved bRFS compared to RP( P=0.018). Risk of biochemical recurrence was significantly lower with BT compared with RP in the patients with a biopsy Gleason grade group 2 and 3 ( P=0.008), or prostate volume ≤35 ml ( P=0.027), or tPSA ≤10 ng/ml ( P=0.013), or the clinical T stages of T 2b and T 2C( P=0.031), or in the intermediate-risk group according to NCCN risk classification ( P=0.003). On multivariate analysis of all 745 patients, age≤ 70 and T stage≥T 2b was associated with significantly shorter bRFS. Conclusions:BT produced equivalent cRFS, CSS and OS compared to RP, while it was associated with improved bRFS. BT On multivariate analysis of all 745 patients, age≤ 70 and T stage≥T 2b was associated with significantly lower bRFS.

Objective To assess the long-term outcome of unilateral adrenaletomy in patients with adrenocorticotropic hormone independent macronodular adrenal hyperplasia (AIMAH).Methods The data from 82 cases of AIMAH were reviewed and summarized including clinical manifestations, endocrinological data, imaging findings and postoperative follow-up.Fouty-nine males and thirty-three females with a mean age of fifty years composed our series.Among the 82 cases, 41 demonstrated Cushing syndrome (CS), 74 presented with hypertension, 38 manifested diabetes mellitus, 35 complicated of osteoporosis and 11 of them with bone fracture, 39 complained of edema.Laboratory tests showed low ACTH plasma levels (＜ 2.2 pmol/L) in 62 of 79 cases.High level of 24-hour urinay free cortisol excretion(＞ 284.2nmol/L) was found in 67 of 79 cases.Elevated serum cortisol with loss of the circadian rhythm was presented in 55 of 60 cases.Failed to suppress cortisol secretion was observed in 61 of 63 conducted with low-dose dexamethasone suppression tests and in 47 of 53 implemented with high-dose dexamethasone suppression tests.Bilateral massively enlarged multinodular adrenal glands were found in all cases with CT or MR imaging.Unilateral adrenalectomy was performed in the larger side of adrenal gland in all 82 cases.All adrenalectomies were carried out including 47 in right sides and 35 in left sides, with 77 by retroperitoneoscopic approach and 5 by open retroperitoneal approach.Results Histopathological examination confirmed nodular hyperplasia of the adrenal cortex for all specimens.After a mean duration of 48.5 months, 80 of 82 patients were available for follow-up.Most clinical symptoms resolved within 6 months after operation.Cushingoid features disappeared in 58.5％ (24/41)of patients who initially presented with typical signs of Cushing Syndrome.Weight loss was seen in 56.3％ (45/80).Improvement of hypertension and diabetes was observed in 63.5％ (47/74) and 76.3％ (29/38) respectively.All the eyelids swelling and edema of the limbs subsided within 3 months.In long-term follow-up (more than 6 months), 82.9％ (63/76) had clinical and biochemical recurrence within a mean time of 14.6 months and 46.0％ (29/63) received contralateral adrenal surgery.Two patients died, one died from heart attack and another one died from pulmonary infection, 2 years and 7 years after unilateral adrenalectomy, respectively.Conclusions Unilateral adrenalectomy just has transient efficiency for AIMAH.Most patients will experience clinical and biochemical recurrence for a long period,and have to receive another operation for the contralateral hyperplastic adrenal gland.

Objective To investigate the clinical presentations,pathologic features,treatment and prognosis of lymphoepithelioma-like carcinoma(LELC)in the upper urinary tract. Methods A case with LELC of the ureter was retrospectively analyzed.A 81-year-old female patient was hospitalized because of gross hematuria for 1 month. CTU demonstrated a 2.5cm tumor in the left ureter.Radical nephroureterectomy was performed laparoscopically. Results Pathologic findings showed invasive poorly differentiated carcinoma in a prominent lymphocytic background.The diagnosis was LELC of the ureter.Epstein-Barr virus in situ hybridization was negative.No disease progression was noted at 3-month foUow-up. Conclusions LELC of the upper urinary tract is rare.All the cases are diagnosed pathologically.The disease eould be treated with radical surgery.Although the differentiation of the tumour cells is poor,the prognosis of pure subtypes seems to be better than that of other types of urothelial carcinoma.

Objective To analyze the clinical and pathological features of the adrenal primitive neuroectodermal tumors(PNET). Methods Four cases of PNET were analyzed.Of them,2 were males and 2 females,aged from 21 to 30 years old with a mean age of 24.No significant abnormal data was found in routine laboratory and endocrine examinations.The CT scan showed a soft tissue mass with unclear boundary and cystic changes in adrenal area.The tumor diameter was 8-17 cm. Results One patient refused treatment alter diagnosed by biopsy and died 6 months later.Another one received palliative operationand died after 8 months.The third patient was found distant metastasis 1 month after operation and had radiotherapy and chemotherapy.The fourth patient was found local tumor recurrence 1 month after operation,and started chemotherapy.All patients were diagnosed by pathology.At HE staining,tumor was consisted of even,uniform small round cells;the cells distributed diffusively or formed lobulated structures (Homer-Wright rosette).Immunohistochemical staining showed CD99 positive in all 4 patients. Canclusion The adrenal PNET is a rare disease originated from primitive neuroectodermal,mostly occurs between 20 and 30 years old,and has non-specific clinical and imaging findings.Histopathologieal examination is the key point for diagnosis.Rapid progression,highly malignant,poor prognosis are the characteristics of this disease.

Objective To explore the clinical features, treatment and prognosis of mucinous tubular and spindle cell carcinoma of the kidney. Methods Patient 1, a 42-year-old woman presented with space-occupying lesion of the lower pole of the left kidney with no symptoms in physical examination for 1 week. CT revealed a low-enhanced tumor located in the lower pole of the left kidney in cT1b N0M0. Radical left nephrectomy was performed. Patient 2, a 76-year-old woman presented with space-occupying lesion of the middle of the left kidney with no symptoms in physical examination for 10 d. CT revealed a low-enhanced tumor located in the middle of the left kidney in cT1b N0 M0. Laparoscopic radical left nephrectomy was performed. The patient received adjuvant treatment with IL-2 and interferon-α 3 months after nephrectomy. Patient 3, a 50-year-old woman presented with lumbago for 3 months. CT revealed a low-enhanced tumor located in the right kidney in cT2 N0 M0. Radical right nephrectomy was performed. The patient received adjuvant treatment with IL-2 and interferon-α 3months after nephrectomy. Patient 4, a 60-year-old woman presented with lumbago and hematuria for 15 d. CT revealed a low-enhanced tumor located in the lower pole of the left kidney in cT1a N0M0.Radical left nephrectomy was performed. Results Histological examination of the tumors showed that they consisted of spindle cells arranged in tubular and trabecular patterns embedded in a myxoid stroma. Pathologic diagnosis of all 4 patients were MTSCCa. There was no evidence of recurrence in all patients for 9- 46 months. Conclusions MTSCCa is a rare low-grade renal cell carcinoma.There is a female predominance. Early surgical excision is the best treatment and the prognosis is relatively good.

OBJECTIVE: To investigate the value of sentinel lymph node of papillary thyroid carcinoma exploring and measuring in the metastasis of the cervical lymph node of thyroid carcinoma. METHOD: The sentinel lymph node were investigated by injecting the methylene blue around 25 cases of thyroid tumors. The lymph nodes dyed in blue and obtained from selective lymph node dissection were examined by pathology, respectively. The value of the sentinel lymph nod were evaluated. RESULT: The sentinel lymph nodes dyed in blue were identified in 22 cases which account for 88.0% of all the 25 cases. Nineteen cases of the sentinel lymph node were positive by pathology, of whom 13 cases were verified positive in other area. Six cases were negative. CONCLUSION It is of great value that sentinel lymph node of thyroid carcinoma can indicate the metastasis of the cervical lymph node of thyroid carcinoma.
Adenocarcinoma, Papillary ; pathology ; surgery ; Adult ; Aged ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Sentinel Lymph Node Biopsy ; Thyroid Neoplasms ; pathology ; surgery ; Young Adult