Volume 104 · Issue 04 · 2024

More and more clinical evidence confirms that hypopituitary dysfunction can lead to liver cirrhosis. The causes of hypopituitary dysfunction include sellarneoplastic diseases, hereditary diseases, perinatal adverse events, etc. Clinically, growth hormone deficiency (GHD) often the first cause in hypopituitary dysfunction.Hypopituitary dysfunction, especially GHD, can lead to liver cirrhosis, which in turn can result in damage to multiple organs such as the secondary lungs, spleen, and heart.Therefore, its clinical manifestations are complex, and the patients are first diagnosed in various departments.Reliable clinical observations have shown that GH replacement therapy at the early stage of the disease can effectively prevent and reverse the progression of cirrhosis, or even avoid inappropriate or unnecessary combined transplantation of liver or liver-related organs.Multidisciplinary collaboration and attention to the new findings that hypopituitary dysfunction can lead to liver cirrhosis will help to improve the accurate diagnosis and treatment of liver cirrhosis.

Human gene editing technology is a hot spot and focus in the development of biotechnology, but it has also caused controversies over technical risks, genetic biosecurity, ethical dignity of human society and the legality of application, causing people to worry about the application of this technology. Gene editing for reproductive purposes is generally prohibited internationally, and countries have established legal regulatory systems to regulate the application of gene editing technology according to their own conditions. China shall establish a security risk access system for gene editing technology, ensure national biosecurity, establish and improve the system of ethical norms for scientific research, improve the construction of legislative standardization, and provide legal guarantees for the research and application of gene editing technology.

Craniopharyngioma is a sellar tumor with benign pathology and malignant clinical manifestations. Partial resection plus radiotherapy, internal radiation therapy and chemotherapy are the conventional treatment strategies forcraniopharyngioma in most hospitals, which cause many patients to lose the best time to cure and make reoperation more difficult after recurrence. Therefore, the Pediatric Group of Chinese Society of Neurosurgery, Chinese Medical Association organized domestic experts from Pediatrics, Pediatric Neurosurgery, Genetics and Endocrinology to reach a consensus on the following topics: pathological and molecular genetic classification of craniopharyngioma, basic principles of curing tumors, surgical classification of tumors, surgical approach, perioperative and long-term treatment plan. This is expected to improve the quality of life and prognosis of patients, and further standardize the diagnosis and treatment of craniopharyngioma.

To evaluate the feasibility and safety of transcatheter tricuspid valve edge-to-edge repair guided by only transesophageal echocardiography (TEE).

Patients with severe tricuspid regurgitation in Fuwai Yunnan Cardiovascular Hospital who met the inclusion criteria based on clinical and echocardiographic evaluationand underwent transcatheter tricuspid valve edge-to-edge repair between January 2022 and May 2023 were prospectively enrolled. The procedure was performed under general anesthesia with endotracheal intubation and solely guided by TEE. The patients underwent clinical evaluation, electrocardiogram and transthoracic echocardiography one month after the procedure.

A total of 22 patients (12 males and 10 females) were included, with an average age of (71.3±6.7) years. All 22 patients successfully underwent the transcatheter tricuspid valve edge-to-edge repair under TEE guidance, with an average of (1.5±0.6) clips implanted. Immediately after procedure, six patients had no or trace regurgitation, 15 patients had mild regurgitation, and one patient had moderate regurgitation. All 22 patients completed 30-day follow-up, with four patients having trace regurgitation, 17 patients having mild regurgitation, and one patient having moderate regurgitation. Echocardiographic measurements revealed that effective regurgitant orifice area, regurgitant volume, vena contracta width, and proximal isovelocity surface area radius significantly decreased after the procedure (all P<0.05). In addition, inferior vena cava width, right atrial volume, tricuspid annular diameter, and right ventricular end-diastolic diameter significantly improved (all P<0.05), but tricuspid annular plane systolic excursion and right ventricular fractional area change did not show significant differences compared with those before the procedure (both P>0.05).

It has been preliminarily confirmed that transcatheter tricuspid valve edge-to-edge repair solely guided by TEE is feasible and safe, but requires more large-scale studies for further validation.

To investigate the brain aging in patients with cirrhosis and hepatic encephalopathy(HE), constructed a prediction model of brain age based on deep learning and T₁ high-resolution MRI, and try to reveal the specific regions where cirrhosis and HE accelerating brain aging.

A cross-sectional study. A brain age prediction model based on the 3D full convolutional neural network was constructed through T₁ high-resolution MRI data from 3 609 healthy individuals across eight global public datasets. The mean absolute error (MAE) between actual age and predicted brain age, Pearson correlation coefficient (r) and determination coefficient (R²) were calculated to evaluate the accuracy of the model′s predictions. A test set (n=555) from the Human Connectome Project was used to assess the accuracy of the model. A total of 136 patients with cirrhosis were recruited from Tianjin First Central Hospital as the case group (79 patients with cirrhosis without HE and 57 patients with cirrhosis with HE), and 70 healthy individuals were recruited from the society as the healthy control group during the same period. Brain-predicted age difference (Brain-PAD), digital connection-A (NCT-A) and digital-symbol test (DST) scores of all subjects were calculated for all subjects to assess brain aging and cognitive function in the healthy control group, the cirrhosis without HE group, and the cirrhosis with HE group. The network occlusion sensitivity analysis method was employed to assess the importance of each brain region in predicting brain age.

As for the prediction model, in the training set, MAE=2.85, r=0.98, R²=0.96. In the test set, MAE=4.45, r=0.96, R²=0.92. In the local data set of the healthy control group, MAE=3.77, r=0.85, R²=0.73. The time of NCT-A in both cirrhosis groups was longer than healthy control group, while the DST scores were lower than healthy control group, and the differences were statistically significant (both P<0.001); the Brain-PAD of healthy control group was (0.8±4.5) years, the Brain-PAD of no-HE group was (6.9±8.1) years, and the HE group was (10.2±7.7) years. The differences between the three groups were statistically significant (P<0.001), and the differences between any two groups were statistically significant (all P<0.05). The importance ratio of visual network in predicting brain age increased in cirrhosis patients, and the HE group was higher than no-HE group.

In patients with cirrhosis, the cognitive function is reduced, brain aging is accelerated, and these changes are more obvious in patients with HE. The importance differences of each brain network in predicting brain aging provide a new direction for identifying the specific regions where cirrhosis and HE accelerate brain aging.

To explore the feasibility and application value of arterial spin labeling (ASL) in evaluating the degree of renal fibrosis after kidney transplantation.

This is a cross-sectional study. Renal transplant recipients who received treatment at the First Affiliated Hospital of Soochow University from December 2021 to December 2022 were enrolled. All participants underwent ASL scan, and the values of renal cortical renal blood flow (RBF) were measured through post-processing software. The participants were divided into different groups according to the Banff interstitial fibrosis score (ci score) of the transplanted kidneys, and then relevant indicators were compared. One-way analysis of variance was conducted to compare the differences in renal cortical RBF among the groups. Spearman correlation analysis was employed to investigate the association between renal cortical RBF and ci score of the transplanted kidney. Receiver operating characteristic curve was used to analyze the diagnostic effectiveness of renal cortical RBF and laboratory indicators for distinguishing varying degrees of fibrosis in transplanted kidneys. The Delong test was utilized to compare the area under the curve (AUC).

A total of 60 patients (42 males and 18 females) were included in the study, with a mean age of (44.6±10.8) years. All patients were divided into 4 groups: ci0 group (ci score=0, 11 cases), ci1 group (ci score=1, 21 cases), ci2 group (ci score=2, 20 cases), and ci3 group (ci score=3, 8 cases). With an increase in the degree of fibrosis in the transplanted kidney, there was a corresponding decrease in the renal cortical RBF value. The differences in renal cortical RBF values among the 4 groups were statistically significant[ci0 group: (214.9±28.5) ml·(100 g)^-1·min^-1; ci1 group: (181.7±29.3) ml·(100 g)^-1·min^-1; ci2 group: (158.8±39.2) ml·(100 g)^-1·min^-1; ci3 group: (123.1±27.2) ml·(100 g)^-1·min^-1; F=14.02, P<0.001]. The renal cortical RBF was moderately negatively correlated with the ci score (r=-0.644, P<0.001). The AUC for discriminating between ci0 and ci1-3 of renal cortical RBF and 24-hour urine protein was 0.881 (95%CI: 0.772-0.950) and 0.680 (95%CI: 0.547-0.795), respectively. The AUC for renal cortical RBF was significantly higher than that for 24-hour urine protein (P=0.047). The renal cortical RBF can distinguish between ci0-1 and ci2-3, as well as ci0-2 and ci3, with the corresponding AUC value of 0.796 (95%CI: 0.673-0.889) and 0.900 (95%CI: 0.795-0.963), respectively.

ASL can quantitatively assess renal blood perfusion in transplanted kidneys and demonstrates high operational efficacy in distinguishing varying degrees of fibrosis in the transplanted kidneys.

To compare the efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer.

A retrospective analysis was conducted on the data of 1 241 patients with driver gene-negative, unresectable stage ⅢB to Ⅳ non-small cell lung cancer who were treated at the Hunan Cancer Hospital from January 1, 2017 to October 1, 2022. All patients received monotherapy or combination therapy with domestic immune checkpoint inhibitors or pembrolizumab. Among the 1 241 patients, there were 1 066 males and 175 females, with an age range of 14 to 84 years and a median age of 62 years. Among them, 67 patients received monotherapy with domestic immune checkpoint inhibitors, 695 patients received combination therapy with domestic immune checkpoint inhibitors, 102 patients received monotherapy with pembrolizumab, and 377 patients received combination therapy with pembrolizumab. The efficacy and safety of domestic immune checkpoint inhibitors and pembrolizumab monotherapy or combination therapy were compared.

In the immune checkpoint inhibitor monotherapy group, the objective response rate (ORR) using domestic immune checkpoint inhibitors and pembrolizumab was 43.3%(29/67) and 44.1%(45/102), respectively, and the disease control rate (DCR) was 79.1%(53/67) and 84.3%(86/102), respectively, with no statistically significant differences (both P>0.05). In the immune combination therapy group, the ORR using domestic immune checkpoint inhibitors and pembrolizumab was 60.9%(423/695) and 62.9%(237/377), respectively, and the DCR was 92.9%(646/695) and 91.0%(343/377), respectively, with no statistically significant differences (both P>0.05). In the immune checkpoint inhibitor monotherapy group, the median progression-free survival (PFS) using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 3.0-15.0) months and 7.4 (95%CI: 4.8-9.8) months, respectively, with no statistically significant differences (P=0.660). The median overall survival (OS) was 27.0 (95%CI: 25.0-29.0) months and 22.0 (95%CI: 17.1-26.9) months, respectively, with no statistically significant differences (P=0.673). In the immune combination therapy group, the median PFS using domestic immune checkpoint inhibitors and pembrolizumab was 9.0 (95%CI: 8.2-9.8) months and 10.5 (95%CI: 9.0-12.0) months, respectively, with no statistically significant differences (P=0.186). The median OS was 24.0 (95%CI: 19.1-28.9) months and 26.0 (95%CI: 21.3-30.7) months, respectively, with no statistically significant differences (P=0.359). The incidence of grade 1-2 reactive capillary proliferation of the skin in the domestic immune checkpoint inhibitor group and pembrolizumab group was 14.0% (107/762) and 0, respectively. The incidence of grade≥3 reactive capillary proliferation of the skin was 1.0% (7/762) and 0, respectively, with statistically significant differences (both P<0.05). No statistically significant differences were observed in other adverse reactions (all P>0.05).

The efficacy of domestically produced immune checkpoint inhibitors is comparable to that of pembrolizumab in the treatment of driver gene-negative advanced non-small cell lung cancer. There is little difference in safety, except for the specific difference in domestically produced immune checkpoint inhibitor, which has a unique risk of reactive cutaneous capillary endothelial proliferation.

To investigate the safety and efficacy of Hepatic Arterial Infusion Chemotherapy(HAIC) combined with targeted and immune therapy followed by ¹²⁵I seeds implantation in portal vain tumor thrombus (PVTT) in the treatment of hepatocellular carcinoma(HCC) with PVTT.

A retrospective study was performed on the clinical data of 21 patients [ (11 men, 10 women) aged 34-73 (52.6±13.7) years] with HCC with PVTT in The First Affiliated Hospital of Zhengzhou University from October 2020 to October 2022, all of them were treated with HAIC plus targeted and immune therapy,and ¹²⁵I seeds implanted into PVTT. The patients were followed up to January 2023, the efficacy was evaluated according to the modified version of the solid tumor efficacy evaluation criteria (mRECIST). The progression-free survival (PFS) rate, overall survival(OS) rate and portal tumor thrombus control rate at 3, 6, 12 and 18 months after treatment were recorded, and PFS and OS time were followed up. The changes of liver function, AFP, coagulation function and adverse events were observed.

Each patient received 2 to 7 (mean: 3.3±1.2) cycles of HAIC. 10-37 seeds (mean:16.6±6.7) were implanted per patients. The median follow-up time was 15 (range from 5 to 25) months.During the follow-up time, 15 patients showed progression and 6 patients died, and the PFS rates at 3, 6, 12, and 18 months after treatment were 90.5%, 71.4%, 42.9%, and 23.8%, respectively, and at 3, 6, 12, and 18-month OS rates were 100%, 100%, 81.0%, and 61.9%, respectively.The PVTT control rates at 3, 6, and 12 months were 90.5%, 90.5%, and 62.5%, respectively. Overall efficacy evaluation of CR rate 0, PR rate 47.6% (10/21), SD rate 38.1% (8/21), and PD rate 14.3% (3/21). The total incidence of treatment-related adverse events was 100%.Grade 3 treatment related adverse events were observed for 4 cases, the rest wereⅠtoⅡadverse events. Right upper abdominal pain, fever and hemorrhage in liver capsule related to the procedures were observed in 11(52.4%), 5(23.8%) and 3(14.3) patients, respectively.

HAIC combined with targeted and immune therapy followed by ¹²⁵I seeds implantation in PVTT is a safe and efficacy therapy for HCC with PVTT.

The purpose of this study was to explore the value of the "improved double purse-string suture method" for pancreatojejunostomy in laparoscopic pancreaticoduodene-ctomy.

The clinical data of 273 patients who underwent laparoscopic pancreaticoduode-nectomy in the Department of Hepatobiliary and Pancreatic Surgery of the First Hospital of Jilin University from January 2021 to May 2022 were retrospectively analyzed. According to the method of pancreaticoenteric anastomosis, the patients were divided into two groups: the "improved double purse-string suture method" group and the "Hong′s one-stitch method" group.

The "improved double purse-string suture method" for pancreaticoenteric anastomosis was performed in a total of 189 patients, including 107 males and 82 females, with a mean age of (59.6±10.2) years. The "Hong′s one-stitch method" group" was performed in a group of 84 patients, including 52 males and 32 females, with a mean age of (60.8±9.3) years.The results showed that the "improved double purse-string suture method" group had a lower incidence of postoperative pancreatic fistula (6.88% vs 8.33% for grade B fistula, and 1.58% vs 2.38% for grade C fistula) and a shorter anastomosis time [(25.25±4.73) min vs (25.76±6.71) min] than the "Hong′s one-stitch method" group. There was no statistically significant difference between the two groups in terms of postoperative biliary fistula, abdominal bleeding, delayed gastric emptying, and other complications (P>0.05).

The "improved double purse-string suture method" for pancreatojejunostomy is safe and feasible in laparoscopic pancreaticoduodenectomy.

Wastewater-based epidemiology (WBE) is an emerging discipline, which has been applied to drug abuse tracking and infectious disease pathogen surveillance. During the COVID-19 epidemic, WBE has been applied to monitor the epidemic trend and SARS-CoV-2 variants etc. In order to detect hidden COVID-19 cases and prevent transmission in the community, wastewater surveillance system for monitoring SARS-CoV-2 RNA was developed in Shenzhen. The sewage sampling sites were set up in key places such as the port areas, urban villages and residential communities of Futian, Nanshan, Luohu and Yantian districts. From July 26 to November 30, 2022, a total of 369 sewage sampling sites were set up, covering 1.93 million people. Continuous sampling was carried out for 3 hours in the peak period of water use every day. Sewage virus enrichment and SARS-CoV-2 nucleic acid detection were carried out by polyethylene glycol precipitation method and RT-qPCR, and a positive water sample disposal process was molded. This article aims to introduce the case of source tracing of COVID-19 infected patients based on urban sewage in Shenzhen. The sewage monitoring of Honghu water treatment plant in Luohu District played an early warning role, and the source of infection was traced. In the disposal of positive water samples in Futian South Road, Futian District, the important experience of monitoring point layout was obtained. In the sewage monitoring of Nanshan village, Nanshan District, the existence of occult infection was revealed. Sharing the experience of tracing the source of COVID-19 patients to avoid the spread of COVID-19 in the community based on wastewater surveillance of SARS-CoV-2 RNA in Shenzhen, and summarizing the advantages and application prospects of sewage surveillance can provide new ideas for monitoring emerging or re-emerging pathogens that are known to exhibit gastrointestinal excretion in the future.

Hypopituitarism is more common in sellar tumors and postoperatively, often leading to growth hormone deficiency (GHD). Long-term GHD can cause disorders of substance metabolism and non-alcoholic fatty liver disease (including simple hepatic steatosis, non-alcoholic steatohepatitis, liver cirrhosis). Hepatopulmonary syndrome is a late complication caused by liver cirrhosis, and the prognosis of hepatopulmonary syndrome is poor. Liver transplantation is the only treatment for hepatopulmonary syndrome. Data show that hepatopulmonary syndrome accounts for 5% to 30% of liver transplantation patients. This article reports a young woman who underwent surgical resection for craniopharyngioma. After operation, panhypopituitary function was reduced but growth hormone replacement therapy was not standardized. 10 years after operation, she developed chest tightness and choking. She was diagnosed as liver cirrhosis and hepatopulmonary syndrome. The symptoms were relieved after treatment with physiological dose of recombinant human growth hormone. By analyzing and summarizing the diagnosis and treatment process of this case, it provides clinical experience for the diagnosis and treatment of hepatopulmonary syndrome in patients with long-term hypopituitarism, and suggests that early diagnosis and timely initiation of growth hormone replacement therapy can help improve the prognosis of patients and reduce the incidence of liver transplantation.

A case of a 5-year-old child with flat face, long and narrow skull in shape of navicular, wide distance between eyes, retarded language development and mild neuromotor retardation was reported. Peripheral venous blood was collected from patients and their parents for whole exon sequencing of genomic DNA. Diagnosis of autism spectrum disorder (ASD); The pregnancy age of the patient's parents was 25/26 years old, and there was no abnormality during pregnancy; There was a base mutation in the SHANK2 gene exon25 in the patient (c.4295C>T). The mutation came from the mother, but the mother was mentally normal and did not have an ASD phenotype. The mutation was first reported. SHANK2 gene is a high-confidence ASD risk gene. So far, 131 variants have been found, of which 24 are inherited in families (19 maternal lines and 5 paternal lines) and 32 new mutations. The SHANK2 gene encodes a protein that connects postsynaptic membrane excitatory receptors with actin, plays a role in dendritic spines and synaptic junctions, and its mutations may manifest as ASD and mental retardation.

The means of primary prevention of hereditary deafness include preimplantation genetic testing (PGT). Currently, hereditary deafness PGT uses whole genome amplification technology to amplify genetic material in trophoblastic ectodermal cells, and detect aneuploidy by microarray comparative genome hybridization (aCGH) technology, microarray single nucleotide polymorphism (SNP-array) and second-generation sequencing technology, combined with linkage analysis to determine the presence of pathogenic deafness gene mutations. In recent years, with the development of non-invasive screening technology, methods have emerged to evaluate the quality, developmental potential and aneuploidy of embryos by using omics of embryo culture medium and free DNA detection. This article mainly reviews the technical process, clinical application and non-invasive screening of PGT in the field of prevention and control of hereditary deafness.