Volume 104 · Issue 26 · 2024

Standard treatment for patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) whose larynx could not be preserved surgically consists mainly of concurrent chemoradiotherapy (CCRT). Induction chemotherapy (ICT) followed by radiotherapy or chemoradiotherapy is also an alternative option. However, whether ICT could provide survival benefits for patients with LAHNSCC, besides its role in laryngeal preservation and selecting the treatment modality, is still controversial. The article summarizes the current position of ICT for LAHNSCC and discusses the standard regimen of ICT, its role in larynx preservation, its ability to predicting the result of chemoradiotherapy, clinical outcomes regarding the survival benefits after ICT, its role in the treatment deintensification for human papillomavirus-positive LAHNSCC and its application in the era of immunotherapy.

Birth defect and perinatal death are major public issues threatening the health of women and children in China. However, perinatal death attributed to birth defects has not yet received sufficient attention. To minimize the occurrence of perinatal death caused by birth defects, this review article deeply analyzed the current status of epidemiology, clinical, and basic research on perinatal death attributed to birth defects both domestically and internationally, and proposed to encourage the conduct of national research on perinatal causes. We should also pay attention to the application of the perinatal cause of death classification system, and focus on accurate diagnosis and the three-level prevention and control of perinatal death attributed to birth defect.

The establishment of clinical research resource platforms, including research databases and bio-sample library, is an important development in the field of clinical research. The international academic community proposes broad informed consent to regulate the ethical management of the issue. However, the broad informed consent fails to capture the main features of incomplete informed consent and authorization, misleads researchers and managers and leads to miss ethical management for clinical research projects. Therefore, the author proposes a named partial informed consent to improve ethical management for clinical research projects. Partial informed consent separates ethical management for establishing clinical research resource platforms and clinical research projects. After reviewing the legal and ethical foundation of clinical research ethics management, the author discussed the similarities and differences between project management and task management in the two informed consent solutions, the basis for approval of exempted informed consent signatures by the ethics committee, issues to be noted in the ethics management of multi-center research at the task level, and explained the substantive differences between broad informed consent and partial informed consent.

Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that has been used in newborns, children, and adults with various cardiopulmonary diseases to reduce pulmonary artery pressure and improve oxygenation. Currently, there are numerous brands of iNO devices on the market with significant differences in performance, as well as variations in connection and setup. Additionally, adverse reactions such as methemoglobinemia may occur during iNO treatment. Therefore, the safety and efficacy of this treatment need to be ensured in clinical practice. To address these concerns and standardize the clinical application of iNO therapy, the Respiratory Care Group of Chinese Thoracic Society and Respiratory Therapist Working Group of Respiratory Career Development Committee, Chinese Association of Chest Physician have organized relevant experts to develop an expert consensus on the clinical application of iNO therapy based on the latest research progress and clinical operational experience. This consensus includes 11 expert consensus recommendations on indications and contraindications of iNO, selection and connection of iNO devices, dose selection and therapeutic effect evaluation of iNO, adverse effects and occupational protection during iNO treatment, transport of patients with iNO, weaning of iNO, cleaning, disinfection and maintenance of iNO devices, and iNO clinical use process and records. The aim is to improve the cognitive and practical ability of clinical practitioners for the standardized application of iNO therapy, so as to ensure the safety and effectiveness of clinical application of iNO therapy.

To compare the efficacy and safety of carrelizumab combined with the modified TPF regimen (docetaxel, cisplatinand capecitabine) and TPF regimen alone in larynx preservation strategy for locally advanced resectable hypopharyngeal squamous cell carcinoma.

A cohort study was conducted. Patients with locally advanced resectable hypopharyngeal carcinoma (cT3-4aN0-3bM0) who were treated at the Eye & ENT Hospital of Fudan University from January 2017 to April 2023 were enrolled in the study. One group was treated with a modified TPF regimen (TPF group) for 2-3 cycles (retrospective data), and the other group was a prospective phase Ⅱ trial with a modified TPF regimen combined with carrelizumab (TPFC group) for three cycles. The patients with complete or partial remission of the primary focus were treated with sequential radical radiotherapy and/or drug therapy. The patients in the TPFC group were treated with carrelizumab at the end of radiotherapy with a maximum of up to 18 doses. The patients with stable or progressive disease were given radical surgery, and those who refused the surgery were given radical chemoradiotherapy. Objective response rate (ORR), overall survival rate, progression-free survival (PFS) rate, larynx preservation rate (LPR), and adverse reactions were compared between the two groups.

There were 51 male patients in the TPFC group, with an median age of 57 (35, 69) years. Meanwhile, 44 patients were in the TPF group, among which 43 were male and one was female, with an median age of 62 (46, 70) years. The ORR of the TPFC group was higher than that of the TPF group [82.4% (42/51) vs 63.6% (28/44), P=0.039]. During a median follow-up of 24.4 (18.5, 31.4) months, the TPFC group showed a higher 2-year survival rate (84.8% vs 64.6%, P=0.013) and 2-year LPR (66.6% vs 48.6%, P=0.045) than those in the TPF group. In patients with poor effect of induction therapy for hypopharyngeal carcinoma, surgical combination therapy significantly prolonged the 2-year PFS rate (77.9% vs 18.2%, P<0.001) and 2-year survival rate (76.9% vs 45.5%, P=0.005)than those of non-surgical combination therapy. The incidences of nausea and/or vomiting, reactive cutaneous capillary endothelial proliferation, thyroid dysfunction, and rash were increased in the TPFC group (all P<0.05). There was no treatment-related death.

Carrelizumab combined with a modified TPF regimen has good efficacy and safety and can improve the LPR of locally advanced hypopharyngeal carcinoma.

To compare the efficacy of gasless robotic surgery through transaxillary approach and open surgery for papillary thyroid carcinoma (PTC).

The data of patient undergoing robotic surgery through transaxillary approach and traditional open surgery for PTC at the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, from November 2016 to June 2023 were retrospectively analyzed. A 1∶1 propensity score matching (PSM) was performed to balance age, sex, extent of surgery, tumor size, capsule invasion, and multifocality. Surgical data, postoperative pathological data, complications, postoperative 2-month visual analog scale (VAS) scores for aesthetics, and follow-up data were compared between the two groups.

A total of 728 PTC patients were included. There were 339 patients in the robotic group, among which 262 were female (77.3%) and 77 were male (22.7%), with the age of [M (Q₁, Q₃)] 39 (32, 46) years and a body mass index (BMI) of 22.8 (20.7, 25.0) kg/m². Meanwhile, 389 patients were in the open group, among which 290 were female (74.6%) and 99 were male (25.4%), with the age of 47 (38, 55) years and a BMI of 23.2 (21.3, 25.5) kg/m². Further analysis after PSM (there were 264 cases in both groups) showed that in the subtotal thyroidectomy and central neck dissection (LT+CCND) subgroup, the robotic group had longer operative time, higher blood loss, and greater drainage volume compared with the open group [100 (80, 130) min vs 60 (50, 80) min; 10 (10, 20) ml vs 10 (10, 20) ml; 103 (69, 145) ml vs 75 (57, 98) ml; all P<0.001], and the central lymph node metastasis rate was higher in the robotic group [45.6% (57/125) vs 31.8% (47/148), P=0.019]. In the total thyroidectomy and central neck dissection (TT+CCND) subgroup, the robotic group also had longer operative time, higher blood loss, and greater drainage volume compared with the open group [150 (110, 180) min vs 85 (75, 100) min; 20 (10, 20) ml vs 10 (10, 20) ml; 155 (107, 206) ml vs 90 (70, 120) ml; all P<0.001]. The incidence of chest skin numbness at 3 months postoperatively was higher in the robotic group compared with the open group (12.9% vs 0, P<0.001), while there were no statistically significant differences in other postoperative complications (all P>0.05). The VAS score at 2 months postoperatively was higher in the robotic group compared with the open group [9 (9, 9) vs 8 (7, 9), P<0.001]. Three cases of contralateral lobe recurrence occurred in the open group, while there were no case of recurrence in the robotic group. The 5-year overall survival rate was 100.0% in both the robotic and open groups, and there was no statistically significant difference in the 5-year disease-free survival rate between the robotic and open groups (100.0% vs 98.6%, P=0.068).

Gasless robotic surgery through transaxillary approach for total thyroidectomy or lobectomy in the treatment of PTC is safe, feasible, and effective, with good cosmetic outcomes and comparable efficacy to traditional surgery.

To investigate the pathological characteristics of tumor regression and the expression level of chemoradiotherapy resistance-related molecular markers after preoperative concurrent radiochemotherapy in patients with locally advanced hypopharyngeal carcinoma.

The clinical data of 44 patients with locally advanced hypopharyngeal carcinoma who underwent preoperative concurrent radiochemotherapy in the Department of Head and Neck Surgery of Shandong Otolaryngology Hospital from August 2016 to August 2020 were retrospectively analyzed. All patients received preoperative concurrent chemotherapy and radiotherapy. After radiochemotherapy, electronic laryngoscopy and imaging examination were performed to assess the tumor regression status. After 4 weeks, surgical resection was performed, and the specimens of the primary focus were processed as continuous pathological sections. After operation, HE staining and TdT-mediated dUTP nick-end labeling (TUNEL) method were used to detect the distribution characteristics and apoptosis of the remaining cancer focus, and immunohistochemistry was performed to determine the proliferation of the remaining cancer focus and the expression of radiation resistance-related molecular markers [signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1alpha (HIF-1α), sex determining region Y-box 2 (SOX2), and P53].

A total of 44 patients were included, all of whom were male, with a mean age of (58.3±3.5) years. There were 40 cases of pyriform sinus carcinoma and 4 cases of posterior pharyngeal wall carcinoma. Twenty-nine cases were in stage T3 and 15 cases were in stage T4. There were 6 stage Ⅲ cases and 38 stage Ⅳ cases. According to the response evaluation criteria in solid tumors (RECIST), 13 patients achieved complete response (CR), 22 patients had partial response (PR), and 9 patients achieved stable disease (SD) after concurrent radiochemotherapy. The primary lesion resection methods included 19 cases of hypopharyngeal circumferential resection and 2 cases of total laryngectomy and partial hypopharyngeal resection. Twenty-three cases underwent supracricoid cartilage subtotal laryngectomy cricoid tongue fixation (CHP). Among 22 patients with PR, 10 had large PR (remission rate ≥70%) and 12 had small PR (remission rate <70%). The residual tumor was found in 30 patients (68.2%) after resection of all primary lesions by HE staining of pathological sections, of which 3 patients (3/13) with CR had residual cancer, all of which were focal residues. In large PR patients, residual cancer was detected in 6 cases (6/10), scattered in 4 cases, and focal residual in 2 cases, respectively. Large residual tumors were detected in small PR and SD patients. TUNEL method did not show any sign of apoptosis in 30 specimens with residual cancer focus, and the positive expression rate of Ki-67 was less than 10%. The expression of STAT3 (3.40±2.49 vs 5.23±3.02, t=-2.932, P=0.007) in 19 cases (63.3%) and HIF-1α (3.73±2.66 vs 6.97±3.05, t=-4.45, P<0.001) in 22 cases (73.3%) of residual cancer were significantly higher than those before radiochemotherapy. Other molecular markers showed no significant changes. All patients were followed up for 3 years. The 2-year survival rate was 59.3%, and the 3-year survival rate was 54.1%.

Preoperative radiochemotherapy can make some patients with locally advanced hypopharyngeal carcinoma achieve complete or significant remission in clinical evaluation, but pathological detection still shows some residual cancer lesions with enhanced anti-apoptosis ability and decreased proliferation activity.

To investigate the relationship between maternal exposures to peri-conceptional risk factors and the risk of hypospadias and cryptorchidism in offspring.

Pregnant women who delivered male newborns and participated in the China birth cohort study between February 2018 and December 2020 at the research center of Beijing Obstetrics and Gynecology Hospital, Capital Medical University were selected for the study. All were enrolled at 6-13⁺⁶ weeks of their gestation. Baseline risk factor information was collected by questionnaire survey. Information on the outcome of hypospadias and cryptorchidism was obtained by clinical examination at birth and ultrasonography. Logistic regression was used to analyze the Odds Ratio (OR) and 95% Confidence Interval (95%CI) of each factor with respect to the onset of the outcome.

A total of 15, 833 pregnant women with an average age of (31.81±3.84) years were included. Among their offsprings, 113 were diagnosed as hypospadias or cryptorchidism (42 hypospadias, 69 cryptorchidism, and 2 both hypospadias and crypterchidism), with an incidence of 7.14‰. The results of multivariate logistic regression analysis showed that mothers with pregnancy history of birth defects (OR=3.01, 95%CI: 1.09-8.35), with preconception Hepatitis B infection (OR=4.74, 95%CI: 1.10-20.42), fetal growth restriction (OR=4.02, 95%CI: 2.10-7.68), multivitamin use since preconception (OR=1.98, 95%CI: 1.12-3.52), and never cook and eat at home (OR=2.17, 95%CI: 1.23-3.82) were risk factors for hypospadias and cryptorchidism (all P<0.05).

Obesity in early pregnancy, preconception Hepatitis B infection, pregnancy history of birth defects, fetal growth restriction, multivitamin use before pregnancy, and rarely cook and eat at home were associated with an increased risk of hypospadias or cryptorchidism in their offsprings.

To analyze the association between maternal blood pressure and congenital heart disease (CHD) in offspring.

From February 2018 to December 2020, pregnant women who participated in the China birth cohort study in Beijing Obstetrics and Gynecology Hospital, Shenzhen Maternal and Child Healthcare Hospital and Chengdu Women′s and Children′s Central Hospital were enrolled in this study. The baseline and follow-up information were collected using an electronic data collection system. Stepwise logistic regression model was used to analyze the association between maternal blood pressure including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure difference (PP) in the first trimester of pregnancy and the risk of CHD in the offspring. A restrictive cubic spline curve was used to draw the dose-response curve between maternal blood pressure and CHD.

A total of 55 552 participants were included in this study. Of them, 31 038, 15 375 and 9 139 pregnant women were enrolled in Beijing Obstetrics and Gynecology Hospital, Shenzhen Maternal & Child Healthcare Hospital and Chendu Women′s and Children′s Central Hospital, respecitively. The age of pregnant women was (31.3±4.0) and the incidence of CHD in the offspring was 0.78% (435/55 552). Multivariable logistic regression model analysis showed that the increase of SBP (OR=1.01, 95%CI: 1.00-1.02), DBP (OR=1.01, 95%CI: 1.00-1.03) and MAP (OR=1.02, 95%CI: 1.00-1.03) in the first trimester were significantly associated with the risk of CHD in the offspring. The restrictive cubic spline analysis showed a positive linear association of SBP (P_total<0.001; P_non-liear=0.315), DBP (P_total<0.001; P_non-liear=0.928) and MAP (P_total<0.001; P_non-liear=0.929) with the risk of CHD in the offspring.

Maternal SBP, DBP and MAP in the first trimester of pregnancy were positively associated with the risk of CHD in the offspring.

To evaluate the application of whole exome sequencing (WES) in the diagnosis of hereditary eye diseases.

A total of 24 patients who came to the Obstetrics and Gynecology Hospital of Fudan University for reproductive genetic counseling from December 2020 to December 2023 with the main complaint of congenital eye disorders were included in this study. All cases had no known infections or exposure to known teratogenic drugs, karyotype and chromosome microarray analysis (CMA) abnormalities. Genomic DNA was extracted from the peripheral blood of the probands and their family members and tested for WES. Among them, three individual WES and 21 Trio WES were performed. Potential pathogenic sites were screened and analyzed by Sanger sequencing. For RPGRIP1:c.1611+26G>A site, minigene vector was constructed and RT-qPCR was performed to detect the effect of mRNA splicing.

A total of 24 families were collected in this study, of which 20 yielded positive results, achieving a diagnosis rate of 83.3% (20/24). The results involved 21 genes and identified 30 distinct variants, 19 of which were new variants reported. Prenatal diagnostic analysis of family 3 revealed that the fetus carried a c.6970G>T heterozygous nonsense mutation in the PRPF8 gene. The results of RT-PCR with the minigene vector at the non-classical splice site in family 24 indicated that the transcription product of the mutant plasmid was partially retained 104 bp in intron 12, resulting in a p.Glu538Valfs*12 alteration of the protein.

The high detection rate of WES in the diagnosis of hereditary eye diseases further supports the advantages of its application as an important molecular detection tool for determining the etiology of hereditary eye diseases.

A total of 82 patients and healthy subjects in the First Affiliated Hospital of Sun Yat-sen University from March to August 2023 were recruited. The cohort consisted of 43 patients with head and neck squamous cell carcinoma (HNSCC) and 39 non-cancer patients or healthy subjects. There were 63 males and 19 females, with a median age of 62 (46, 67) years. The levels of folate receptor-positive circulating tumor cells (FR⁺CTCs) in the blood of HNSCC patients and non-cancer/healthy subjects were 12.4 (8.5, 17.8) floate unit (FU)/3 ml and 5.0 (3.8, 6.6) FU/3 ml, respectively, with a statistically significant difference (P<0.001). The area under the receiver operating characteristic (ROC) curve for FR⁺CTCs levels was 0.937 (95%CI: 0.888-0.986, P<0.001), with a cut-off value of 7.4 FU/3 ml determined by the maximum Youden index. At this cut-off value, the sensitivity and specificity of FR⁺CTCs for diagnosing HNSCC were 90.70% and 89.74%, respectively. The current study suggests that FR⁺CTCs could be used as a liquid biopsy marker for the screening and diagnosis of HNSCC.

Evaluation of neobladder function in patients with long-term survival and no recurrence after laparoscopic radical cystectomy and intracorporeal Xing′s neobladder. The clinical data of laparoscopic radical cystectomy and intracorporeal Xing′s neobladder in long-term survival patients with bladder cancer treated in Beijing Chaoyang Hospital from July 2013 to July 2018 were analyzed retrospectively. All 17 patients underwent the surgery by the same surgical team, including 15 males and 2 females, whose mean age at the time of operation was (55.9±7.6) years. Thepostoperative urinary function and renal function were summarized. All operations were successfully completed. The mean operative time was (340±62) min. All patients were followed up for a long time, with a median follow-up time of 80(70, 96) months, Urinary continence was achieved in 17 (100%)casesduring the day and 13 (76.5%) cases at night, with a median bladder volume of 350 (200, 400) ml. All patients had good urinary control after surgery, and no hydronephrosis or creatinine increase was found in reexamination.After the application of Xing′s neobladder operation, the patient maintained acceptable urinary control status after the operation, and the long-term follow-up effect was satisfactory.

The patient, a 75-year-old male, went to the First Affiliated Hospital of Zhengzhou University on October 23, 2021 due to "belching for more than 3 months" and was diagnosed with lower esophageal adenocarcinoma. The patient underwent "thoracic and laparoscopic combined radical esophagectomy + lymph node dissection + thoracic duct ligation + pleural adhesion cauterization" under general anesthesia. On the second day after the operation, the patient developed fever, hypoxic saturation and increased thoracic drainage fluid, and the laboratory examination confirmed that he was chylothorax. After conservative treatment, body temperature, oxygen saturation and drainage volume improved. One week after surgery, the patient developed dyspnea and chest CT revealed the formation of a cystic wrap in the mediastinum and compression of the trachea. Combined with laboratory examination of mediastinal drainage fluid and chest CT, the diagnosis of chylomediastinum was confirmed. After conservative treatment failed, "thoracoscopic thoracic duct ligation" and cyst incision and drainage were performed immediately, and the postoperative recovery was good.

Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV + IFDCS) is a rare low-grade malignant tumor characterized by follicular dendritic cell differentiation, which occurs in the liver and spleen. This paper reports a case of primary multiple EBV + IFDCS in the liver, and analyzes its possible pathogenesis, diagnosis, treatment and prognosis in combination with the literature, so as to improve the understanding of this disease and avoid misdiagnosis.

The prevention and control of birth defects is particularly important to improve the quality of our population. Non-invasive prenatal screening (NIPT) based on fetal free DNA in peripheral blood of pregnant women has been widely used in clinical practice, but NIPT cannot achieve the screening of monogenic diseases. The new generation of NIPT technology (NIPT 2.0) enables simultaneous non-invasive prenatal screening for fetal chromosomal abnormalities and single-gene dominant genetic diseases, expanding the range of diseases and improving detection accuracy. This article reviews the research and clinical application status of NIPT at home and abroad, focusing on the clinical application value, technological breakthroughs, clinical research progress and limitations of NIPT 2.0 technology. The clinical popularization and application of NIPT 2.0 technology will further improve the prevention and control level of birth defects.

Imaging examination is very important for the assessment and treatment of pulmonary diseases, but traditional pulmonary magnetic resonance examination cannot observe the lung parenchyma. Hyperpolarization¹²⁹Xe magnetic resonance imaging (MRI) can not only quantitatively analyze the ventilation, diffusion and erythrocyte transport functions of the lungs, but also visually present the local lung function status. At present, good results have been achieved in the diagnosis and evaluation, efficacy evaluation and prognosis prediction of interstitial lung diseases, bronchial asthma, chronic obstructive pulmonary disease, novel coronavirus infection, cystic fibrosis and other lung diseases. Hyperpolarization Now¹²⁹The research progress of XeMRI application in these lung diseases is reviewed.

At present, liver transplantation is the only effective treatment for end-stage liver disease and liver failure, and the reperfusion injury after transplantation affects the success rate of liver transplantation to some extent. Ischemia-reperfusion injury (IRI) includes two stages: ischemia and reperfusion. Its occurrence involves a variety of pathophysiological mechanisms and cell activation, including oxidative stress, inflammatory cytokines, calcium overload, mitochondrial damage, neutrophils and Kupffer cell activation, etc., and reactive oxygen species play an important role in it. Intracellular reactive oxygen species are mainly derived from cytoplasm and mitochondria. The two sources interact and promote each other. Recent studies have found that reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is involved in liver IRI by producing a large number of cytoplasmic reactive oxygen species, mediating oxidative stress, immune cell activation and programmed cell death. In this paper, the latest research progress on the role of NOX in liver IRI (including oxidative stress, immune cell activation, apoptosis, ferroptosis and other programmed cell death) is reviewed.

In addition to genetic factors, certain potentially modifiable maternal factors, such as type I diabetes mellitus (T1D) in pregnant women, have been shown to be associated with an increased risk of congenital heart disease (CHD) in offspring, but the relationship between gestational diabetes mellitus (GD), maternal overweight, and obesity and offspring developing CHD is unclear, especially for specific CHD subgroups. The study prospectively investigated the association of maternal pregnancy with diabetes mellitus (PGD), GD, overweight, and obesity with the risk of developing CHD in offspring in the same model, while also evaluating its association with specific subgroups of isolated CHD.

Chinese Medical Journal, Volume 98, Issue 24, 2018, "Multidisciplinary Diagnosis and Treatment Guidelines for Obstructive Sleep Apnea in Adults", page 1905, left Table 3. The AHI classification in the basis for judging the severity of adult OSA should be: mild AHI 5~<15 times/h, moderate AHI 15~<30 times/h, severe AHI ≥30 times/h. Corrections are hereby made.

Article "Clinical Practice Guidelines for Quality Control of Hemodiafiltration", Volume 104, Issue 8, 2024, Chinese Journal of Medicine, page 578, paragraph 1 "General Reference Standard for Intravenous Infusion of Commercial Replacement Fluids: Endotoxin<0.03 active units (EU) /ml and the number of bacteria<1×10⁶Colony Forming Unit (CFU) /ml "shall be" Commercial Replacement Solution General Reference Intravenous Infusion Standard: Endotoxin<0.03 active units (EU) /ml and the number of bacteria<1×10^-6Colony Forming Units (CFU) /ml ". Corrections are hereby made.

The article "Mechanisms of Heparin Resistance and Clinical Management Strategies", Volume 103, Issue 10, 2023, Chinese Journal of Medicine, pp. 707-708 "The relative molecular mass of LMWH derived from UFH fractional distillation purification is 3 500-5 000^［2］The relative molecular mass of LMWH derived from the depolymerization of UFH by enzymatic or chemical methods is from 3 500 to 5 000^［2］”。 Corrections are hereby made.