[A case of follicular lymphoma with recurrent fever and pulmonary infiltrates].

We reported a case of a 65-year-old male who had been treated with obinutuzumab and chemotherapy for follicular lymphoma. He was infected with SARS-CoV-2 after the second course of therapy. He developed fever, cough and bilateral pulmonary infiltrates. His nasopharyngeal swab became negative only temporarily after repeated courses of antiviral therapy, and the symptoms and pulmonary infiltrates waxed and waned. He presented to our hospital with exertional dyspnea and hypoxemia after his nasopharyngeal swab was positive for SARS-CoV-2 for the fourth time. He had an elevated serum lactate dehydrogenase and a positive 1, 3-ß-D-glucan test. The PCR test for Pneumocystis jirovecii in the sputum was positive. The patient was diagnosed with persistent COVID-19 and Pneumocystis jirovecii pneumonia. He responded well to the combination treatment of antiviral medication, convalescent plasma, trimethoprim-sulfamethoxazole and corticosteroids.

[Analysis of 9 patients with adolescence-onset methylenetetrahydrofolate reductase deficiency].

Objective: To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency. Methods: This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively. Results: The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 µmol/L) was found in all patients, and decreased to 20-70 µmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders. Conclusions: Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.

[Feasibility study of expectant management of different degrees of vaginal fluid in pregnant women with premature rupture of membranes in the second trimester].

Objective: To investigate the feasibility of expectant management of different degrees of vaginal fluid in pregnant women with premature rupture of membranes in the second trimester. Methods: A retrospective cohort study was conducted to collect 103 pregnant women who were diagnosed with premature rupture of membranes in the second trimester of pregnancy and insisted on continuing the pregnancy in Shanxi Bethune Hospital from July 2012 to July 2022. According to the degree of vaginal fluid, pregnant women were divided into rupture group (with typical vaginal fluid, 48 cases) and leakage group (without typical vaginal fluid, 55 cases). The rupture latency (the time from rupture of membranes to termination of pregnancy), gestational weeks of termination, indications and methods of termination of pregnancy, maternal infection related indicators and perinatal outcomes were compared between the two groups. Univariate regression model was used to analyze the correlation between different degrees of vaginal fluid in pregnant women with premature rupture of membranes and maternal and neonatal outcomes. Results: (1) Obstetric indicators: there was no significant difference in the gestational age of rupture of membranes between the two groups (P>0.05). However, the proportion of rupture latency >28 days in the leakage group was significantly higher than that in the rupture group [42% (23/55) vs 13% (6/48); χ2=33.673, P<0.001], and the incidence of pregnancy termination ≥28 weeks was significantly higher [47% (26/55) vs 19% (9/48); χ2=9.295, P=0.002]. (2) Indications and methods of termination: the incidence of progressive reduction of amniotic fluid as the indication for termination in the leakage group was significantly lower than that in the rupture group [22% (12/55) vs 42% (20/48); χ2=4.715, P=0.030], and the incidence of full-term termination in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 12% (6/48); χ2=5.008, P=0.025], while there were no significant differences in the indications of termination of pregnancy, including amniotic cavity infection, uterine contraction failure and fetal distress between the two groups (all P>0.05). The incidence of induced labor or spontaneous contraction in the leakage group was significantly lower than that in the rupture group [53% (29/55) vs 81% (39/48); χ2=9.295, P=0.002], while the cesarean section rate and vaginal delivery rate were similar between the two groups (both P>0.05). (3) Infection related indicators: the incidence of amniotic cavity infection in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 13% (6/48); χ2=4.003, P=0.045]. However, there were no significant differences in the elevation of inflammatory indicators, the positive rate of cervical secretion bacterial culture and the incidence of tissue chorioamnionitis between the two groups (all P>0.05). (4) Perinatal outcomes: the live birth rate in the leakage group was significantly higher than that in the rupture group [51% (28/55) vs 27% (13/48); χ2=5.119, P=0.024]. The proportion of live births with 1-minute Apgar score >7 in the leakage group was significantly higher than that in the rupture group [38% (21/55) vs 17% (8/48); χ2=4.850, P=0.028]. However, there were no significant differences in the birth weight of live births and the incidence of neonatal complications between the two groups (all P>0.05). (5) Univariate regression analysis showed that compared with the rupture group, the leakage group had a higher risk of pregnancy termination at ≥28 gestational weeks (RR=2.521, 95%CI: 1.314-4.838; P=0.002), amniotic infection (RR=2.473, 95%CI: 1.061-5.764; P=0.025), perinatal survival (RR=1.880, 95%CI: 1.104-3.199; P=0.014). Conclusion: Compared with pregnant women with typical vaginal fluid in the second trimester of premature rupture of membranes, expectant treatment for pregnant women with atypical vaginal fluid is more feasible, which could effectively prolong the gestational weeks and improve the perinatal live birth rate.

[Treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations].

Objective: To examine the treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations. Methods: This is a retrospective case series. Clinic data from 24 children with tracheal stenosis who underwent surgical treatment in the Department of Cardiac Surgery, Children's Hospital Affiliated to Shandong University from February 2017 to March 2023 were retrospectively collected. There were 16 males and 8 females, aged (M(IQR)) 6.5 (19.6) months (range: 2.2 to 66.3 months) and weighted 5.95 (4.76) kg (range: 3.2 to 20.0 kg). All patients had obvious respiratory symptoms. Eighteen patients underwent cardiac malformation correction and tracheoplasty at the same time (simultaneous group). Six patients in the staged operation group were treated with cardiac malformation correction in the first stage operation and tracheoplasty in the second stage operation due to missed diagnosis or delayed diagnosis of tracheal stenosis or no condition for tracheoplasty. Slide tracheoplasty was used to correct tracheal stenosis in both groups. The recovery of the children was followed. Wilcoxon sign rank test was used for comparison between the two groups. Results: There was no death during the perioperative period and hospitalization. In the simultaneous group, 1 case with delayed chest closure underwent bedside chest closure after 52 hours, 2 cases were intubated again after operation, and 1 case was implanted with an endotracheal stent. The duration of mechanical ventilation was 40.5 (39.6) hours (range: 19.0 to 438.8 hours). In the staged group, there was 1 case of re-intubation after operation, combined with left vocal cord paralysis and respiratory multidrug-resistant bacterial infection (Acinetobacter baumanii). One patient underwent 3 times of bronchoscopic balloon dilatation of the right middle bronchus, and heart rate returned to normal range. The duration of mechanical ventilation was 19.0 (21.4) hours (range: 17.1 to 96.7 hours). During follow-up, a patient in the simultaneous group was prone to respiratory infection and had good exercise tolerance, 1 patient in the staged group still had sputum stridor in the throat 3 months after the operation, and symptoms improved significantly 6 months after the operation. The other children didn't have obvious respiratory symptoms. Conclusions: The diagnosis of tracheal stenosis may be delayed or missed when tracheal stenosis is complicated by non-vascular ring cardiac malformations. One-stage correction of tracheal stenosis and cardiac malformation can achieve a good outcome.

[Efficacy and short-term outcomes of myocardial protection using single-dose histidine-tryptophan-ketoglutarate cardioplegia during aortic root surgery with different duration of myocardial ischemia].

Objective: To explore the efficacy of myocardial protection with single-dose histidine-tryptophan-ketoglutarate (HTK) cardioplegia during aortic root operation, and the correlation between short-term clinical outcomes and duration of myocardial ischemia. Methods: The data of clinical cases undergoing myocardial protection with single-dose HTK cardioplegia during aortic root operation from January 2018 to December 2022 were retrospectively reviewed. Patients were divided into conventional HTK cardioplegia group (<3 h) and prolonged HTK cardioplegia group (≥3 h) according to duration of intraoperative myocardial ischemia. A 1∶1 propensity score matching was performed and the correlations between duration of myocardial ischemia and postoperative short-term outcomes (30-day mortality, readmission, mechanical circulation support and renal insufficiency) were analyzed. Results: A total of 282 patients were included in the final analysis, with 210 cases in the conventional HTK cardioplegia group and 72 cases inthe prolonged HTK cardioplegia group before matching. After matching, there were 64 cases (53 males and 11 females) in the conventional HTK cardioplegia group, with a mean age of (49.4±14.2) years. The prolonged HTK cardioplegia group had 64 cases (55 males and 9 females), with a mean age of (50.5±12.3) years. Higher sensitivity troponin [12 h: 10.1 (4.6, 18.7) µg/Lvs 4.1(2.2, 8.6) µg/L, P=0.002; 24 h: 7.7 (4.5, 19.0) µg/L vs 4.8 (2.2, 11.9) µg/L, P=0.025] and creatine kinase isoenzyme[12 h: 46.3 (28.1, 62.4) µg/L vs 20.7(14.1, 32.9) µg/L, P<0.001; 24 h: 26.3(13.4, 49.2) µg/L vs 14.5 (10.1, 33.5)µg/L, P=0.011] after surgery was detected in prolonged HTK cardioplegia group. Comparisons of other primary and secondary endpoint events showed no significant differences between the two groups (all P>0.05). Multivariate binary logistic regression showed that duration of myocardial ischemia had no significant effect on postoperative 30-day mortality (OR=1.255, 95%CI: 0.500-3.148, P=0.629), 30-day readmission (OR=0.378, 95%CI: 0.069-2.065, P=0.261) and mechanical circulation support (OR=0.991, 95%CI: 0.331-2.970, P=0.998). Conclusion: During aortic root surgery, single-dose HTK cardioplegia may provide satisfactory myocardial protection, and there was no significant correlation between duration of myocardial ischemia and short-term clinical outcomes.

[Endoscopic diagnosis, treatment and evaluation of iatrogenic biliary stricture].

Iatrogenic biliary stricture is a serious complication after biliary surgery. It can cause recurrent cholangitis, bile duct stones, cholestatic cirrhosis, and even liver failure. The overall effect of traditional surgery is satisfactory, but there are also shortcomings such as large trauma, high difficulty of surgery and poor acceptance of patients. With the development of endoscopic minimally invasive technology, choledochoscopy and duodenoscopy have become important treatment methods for iatrogenic biliary stricture, with the advantages of small trauma, high safety and strong repeatability. How to give full play to the advantages of endoscopic therapy, improve the success rate of stenosis treatment and reduce the recurrence rate is still a topic worthy of discussion.

[Surgical treatment strategy of pulmonary artery sling: a series of 110 cases].

Objective: To examine the effect of surgical treatment in children with pulmonary artery sling and the surgical treatment strategy. Methods: Relevant data of 110 children with pulmonary artery sling admitted to the Department of Cardiac Surgery, Children's Hospital Affiliated to Shandong University from February 2017 to July 2022 were retrospectively analyzed. There were 55 males and 55 females, aging (M(IQR)) 9.0 (10.6) months (range: 1 to 96 months). The weight was 7.8 (3.5) kg (range: 2.5 to 25.0 kg). Of the 110 patients, 108 had different degrees of tracheal stenosis and 2 had normal trachea. Left pulmonary artery transplantation and tracheoplasty were performed in 78 patients. Left pulmonary artery transplantation was performed in 30 patients (11 in our hospital and 19 in other hospitals) due to the lack of an early tracheoplasty technique, in which 24 patients needed stage Ⅱ tracheoplasty due to obvious respiratory symptoms and limited activity endurance, and 6 cases did not intervene. Two children with normal trachea only underwent left pulmonary artery transplantation. Results: Among the 78 children who underwent surgery in the same period, 70 cases recovered smoothly after surgery, of whom respiratory symptoms were significantly reduced or disappeared during the 1 to 65 months follow-up, with similar activity endurance to normal children of the same age. Eight cases died, including 4 cases of postoperative multi-drug resistant bacteria infection, died from tracheal anastomotic opening or septic shock, 1 cases with severe congenital heart disease died from postoperative low cardiac output syndrome difficult to correct, 1 case died from blood pressure could not be maintained due to the compressed left pulmonary artery after transplantation, 2 cases of postoperative digestive system diseases (adhesive intestinal obstruction, gastrointestinal bleeding, etc.). The 24 patients in the staging group were followed for 1 to 84 months. All patients needed stage Ⅱ tracheoplasty due to respiratory symptoms and decreased endurance to activity. Eight cases of the non-intervention tracheal group were successfully separated from the ventilator, cured and discharged in a short period of time. Conclusions: Most children with pulmonary artery sling have tracheal stenosis. Children with low degree of tracheal stenosis and inconspicuous respiratory symptoms can only undergo left pulmonary artery transplantation by lateral thoracotomy. For patients combined with severe tracheal stenosis or obvious respiratory symptoms, a simultaneous left pulmonary artery transplantat and tracheoplasty is recommended.

Comparison of PFNA and DHS in the treatment of sarcopenia with Seinsheimer type V subtrochanteric fracture.

OBJECTIVE: We aimed at comparing the curative effect of proximal femoral nail antirotation (PFNA) and dynamic hip screw (DHS) in the treatment of Seinsheimer type V (type V) subtrochanteric fractures with sarcopenia. PATIENTS AND METHODS: A retrospective analysis was performed on 59 patients with type V subtrochanteric fractures complicated with sarcopenia admitted to the Department of Orthopedics of the affiliated Jiangning Hospital with Nanjing Medical University from January 2016 to December 2021. Sarcopenia was diagnosed based on grip strength and skeletal muscle index (SMI). According to different surgical methods, they were divided into PFNA group (32 cases) and DHS group (27 cases). The age, gender, time from injury to operation, SMI value, incision length, operation time, intraoperative blood loss, fluoroscopy times, perioperative blood transfusion, lower limb full weight-bearing time, visual analogue scale (VAS) for pain at 3 months after operation and at the last follow-up, Harris score as well as postoperative complications were compared between the two groups. RESULTS: There were no significant differences in age, gender, time from injury to operation, and SMI between the two groups. The length of surgical incision, blood loss and blood transfusion in the PFNA group were less than those in the DHS group; however, the number of intraoperative fluoroscopies was more than that in the DHS group. The PFNA group had earlier full weight-bearing time, lower VAS score and higher Harris score at 3 months after operation, while there was no statistically significant difference in VAS score and Harris score between the two groups at the last follow-up. The incidence of complications in the PFNA group was lower than that in the DHS group, and the difference was statistically significant. CONCLUSIONS: Both PFNA and DHS are effective methods for the treatment of type V subtrochanteric fractures complicated with sarcopenia. Strikingly, PFNA is preferred because of its short surgical incision, less blood loss, faster recovery, and lower incidence of complications.

[Metamorphopsia caused by macular choroidal macrovessel: a case report].

A 75-year-old male patient presented to the hospital with metamorphopsia of the left eye for 1 month. The corrected visual acuity of left eye was 0.5. Fundus examination showed leopard fundus, small patches of pigmentation were present in the macular area, depigmentation around the macula,choroidal macrovessel emerged from the macular area in a horizontal, temporal, serpentine pattern, optical coherence tomography showed an abnormally enlarged hypo-reflective cavity occupying the full thickness of the choroid in the subfovea as well as in the temporal side of the macula. Early fundus indocyanine green angiography showed rapid filling fluorescence tracks distributed from macula to the temporal side. The patient was diagnosed with macular choroidal macrovessel based on medical history, ocular multimodal examination and general examination. The patient was not given special treatment, and was instructed to control blood pressure in the department of internal medicine and to follow up regularly in the outpatient clinic of fundus disease.

[Analysis on missed diagnosis or misdiagnosis of anomalous origin of left coronary artery from pulmonary artery by echocardiography from one single medical center].

Objectives: To analyze the reasons of missed diagnosis or misdiagnosis on anomalous origin of left coronary artery from pulmonary artery (ALCAPA) by echocardiography. Methods: This is a retrospective study. Patients with ALCAPA who underwent surgical treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from August 2008 to December 2021 were included. According to the results of preoperative echocardiography and surgical diagnosis, the patients were divided into confirmed group or missed diagnosis/misdiagnosis group. The results of preoperative echocardiography were collected, and the specific echocardiographic signs were analyzed. According to the experience of the doctors, the echocardiographic signs were divided into four types, namely clear displayed, vague/doubtful displayed, no display and no notice, and the display rate of each sign was calculated (display rate=number of clearly displayed cases/total number of cases×100%). By referring the surgical data, we analyzed and recorded the pathological anatomy and pathophysiological characteristics of the patients, and the rate of missed diagnosis/misdiagnosis of echocardiography in patients with different characteristics was compared. Results: A total of 21 patients were enrolled, including 11 males, aged 1.8 (0.8, 12.3) years (range 1 month to 47 years). Except for one patient with anomalous origin of left anterior descending artery, the others were all originated from the main left coronary artery (LCA). There were 13 cases of ALCAPA in infant and children, and 8 cases of adult ALCAPA. There were 15 cases in the confirmed group (diagnostic accuracy was 71.4% (15/21)), and 6 cases in the missed diagnosis/misdiagnosis group (three cases were misdiagnosed as primary endocardial fibroelastosis, two cases were misdiagnosed as coronary-pulmonary artery fistula; and one case was missed diagnosis). The working years of the physicians in the confirmed group were longer than those in the missed diagnosis/misdiagnosed group ((12.8±5.6) years vs. (8.3±4.7) years, P=0.045). In infants with ALCAPA, the detection rate of LCA-pulmonary shunt (8/10 vs. 0, P=0.035) and coronary collateral circulation (7/10 vs. 0, P=0.042) in confirmed group was higher than that in missed diagnosis/misdiagnosed group. In adult ALCAPA patients, the detection rate of LCA-pulmonary artery shunt was higher in confirmed group than that in missed diagnosis/misdiagnosed group (4/5 vs. 0, P=0.021). The missed diagnosis/misdiagnosis rate of adult type was higher than that of infant type (3/8 vs. 3/13, P=0.410). The rate of missed diagnosis/misdiagnosis was higher in patients with abnormal origin of branches than that of abnormal origin of main trunk (1/1 vs. 5/21, P=0.028). The rate of missed diagnosis/misdiagnosis in patients with LCA running between the main and pulmonary arteries was higher than that distant from the main pulmonary artery septum (4/7 vs. 2/14, P=0.064). The rate of missed diagnosis/misdiagnosis in patients with severe pulmonary hypertension was higher than that in patients without severe pulmonary hypertension (2/3 vs. 4/18, P=0.184). The reasons with an echocardiography missed diagnosis/misdiagnosis rate of≥50% included that (1) the proximal segment of LCA ran between the main and pulmonary arteries; (2) abnormal opening of LCA at the right posterior part of the pulmonary artery; (3) abnormal origin of LCA branches; (4) complicated with severe pulmonary hypertension. Conclusions: Echocardiography physicians' knowledge of ALCAPA and diagnostic vigilance are critical to the accuracy of diagnosis. Attention should be paid to the pediatric cases with no obvious precipitating factors of left ventricular enlargement, regardless of whether the left ventricular function is normal or not, the origin of coronary artery should be routinely explored.

[Read-through circular RNA rt-circ-HS promotes hypoxia inducible factor 1α expression and renal carcinoma cell proliferation, migration and invasiveness].

OBJECTIVE: To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays. RESULTS: We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α. CONCLUSION: The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.

[Diagnostic value of lipoprotein-associated phospholipase A2 in OPBR combined with gallbladder cholesterol deposition].

Objective: To study the diagnostic value of lipoprotein-associated phospholipase A2(LP-PL-A2) in occult pancreaticobiliary reflux(OPBR) combined with gallbladder cholesterol deposition. Methods: This was a case-control study. Forty-six patients with OPBR who underwent gallbladder surgery at Shanghai East Hospital from December 2020 to October 2021, with gallbladder cholesterol deposition as the case group and the remainder as the control group, were included for analysis of their clinical data. Results: There were 21 cases in the case group, with 10 males and 11 females, and aged (57±12) years; 25 cases in the control group, with 11 males and 14 females, and aged (56±10) years. Serum LP-PL-A2 [(551.62±128.69) U/L] was significantly higher in the case group than in the control group [(436.70±135.88) U/L] (t=-2.80,P<0.01).Univariate analysis showed that LP-PL-A2 was a risk factor for OPBR combined with gallbladder cholesterol deposition, OR(95%CI):1.007(1.002-1.012), P=0.011. The area under the receiver operating characteristic curve (ROC) curve was 0.742, P=0.005. Conclusion: LP-PL-A2 is of diagnostic value in OPBR combined with gallbladder cholesterol deposition.

[Clinical analysis of the correlation between gallbladder adenomyomatosis and occult pancreaticobiliary reflux].

Objective: To explore the association between gallbladder adenomyomatosis (GA) and occult pancreaticobiliary reflux (OPBR). Methods: A total of 81 patients with GA who underwent cholecystectomy in Shanghai East Hospital from December 2020 to January 2022 were enrolled, including 48 cases of fundal type, 28 cases of segmental type and 5 cases of diffuse type. Patient's intraoperative bile was coltected and tested for amylase. According to gallbladder bile amylase level, patients were divided into OPBR group (bile amylase>110 U/L) and the control group (bile amylase≤110 U/L). Results: Among 81 patients, 32 were male and 49 were female, and aged (49.1±13.2) years; there were 66 cases in control group, including 27 males and 39 females, and aged (50.0±12.9)years; there were 15 patients in the OPBR group, including 5 males and 10 females, and aged (45.1±14.2) years. In terms of the clinical features of the two groups, there was no significant difference (all P>0.05), except for a significant increase in biliary amylase in the OPBR group compared with the control group (P<0.001). However, the incidence of OPBR was significantly different in the three types of GA, with a lower incidence of OPBR in the fundal type (10.4%, 5/48) than in the segmental type (28.6%, 8/28) and diffuse type (2/5) (P=0.038). In addition, segmental GA was more likely to be combined with gallbladder stones (85.7%, 24/28) than fundal GA (58.3%, 28/48) and diffuse GA (3/5) (P=0.031). Univariate and multivariate logistic regression analyses showed OPBR [OR (95%CI)=3.410 (1.010 to 11.513), P=0.048] and combined gallbladder stones [OR (95%CI)=2.974 (1.011 to 8.745), P=0.048] indepenclently correlated with segmental and diffuse GA. Conclusions: The incidence of OPBR is higher in segmental and diffuse GA, and gallstones and OPBR are independently associated with the occurrence of segmental and diffuse GA. These results suggest that OPBR may be the initiating factor for the occurrence and carcinogenesis of segmental and diffuse GA.

[Nontuberculous mycobacteria infection and pulmonary alveolar proteinosis in a patient with hematopoietic defects].

A 28-year-old male with a history of leukopenia was admitted with complaints of fever, cough, and dyspnea for 3 months. Initial work-up identified reduced circulating levels of granulocytes, monocytes, lymphocytes, and NK cells. Computed tomography revealed bilateral reticulonodular opacities and mediastinal lymph node enlargement. Peripheral blood culture and mediastinal lymph node aspiration yielded Mycobacterium avium. Genetic testing revealed a heterozygous germline GATA2 mutation (c.1187G>A, R396Q). Despite standard anti-mycobacterial therapy, the patient's dyspnea worsened and subsequent imaging studies revealed diffuse ground-glass opacification. A transbronchial lung biopsy confirmed the development of pulmonary alveolar proteinosis. Bone marrow transplantation had not been performed due to the unavailability of suitable donors. The disease progressed after whole lung lavage, and the patient died at the age of 31 years from respiratory failure. The current case report emphasized the importance of raising awareness about the rare GATA2 deficiency, which is characterized by hematologic abnormalities, primary immunodeficiency, and pulmonary alveolar proteinosis.

[Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers].

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.