2022年 · 第135卷第04期

Chronic infection of hepatitis B virus (HBV) and hepatitis C virus (HCV) pose a serious public health burden worldwide. In the past three decades, China has made enormous efforts and achieved remarkable progresses in the prevention, diagnosis, and treatment of chronic hepatitis B (CHB) and C (CHC).^[1]

Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs).

A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure.

In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003).

This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.

The European Respiratory Society/American Thoracic Society clinical practice guidelines, which are only recommendatory, suggest utilization of non-invasive respiratory support therapies (NRST) as a preventive strategy for avoiding intubation in hypoxemic acute respiratory failure (ARF).^[1]Theoretical concerns against the use of NRST are essentially related to safety reasons for the risk of the virus spreading among healthcare workers (HCW) and for the risk of delaying intubation in case of failure.

Hypertension is associated with stroke-related mortality. However, the long-term association of blood pressure (BP) and the risk of stroke-related mortality and the influence path of BP on stroke-related death remain unknown. The current study aimed to estimate the long-term causal associations between BP and stroke-related mortality and the potential mediating and moderated mediating model of the associations.

This is a 45-year follow-up cohort study and a total of 1696 subjects were enrolled in 1976 and 1081 participants died by the latest follow-up in 2020. COX proportional hazard model was used to explore the associations of stroke-related death with baseline systolic blood pressure (SBP)/diastolic blood pressure (DBP) categories and BP changes from 1976 to 1994. The mediating and moderated mediating effects were performed to detect the possible influencing path from BP to stroke-related deaths. E value was calculated in the sensitivity analysis.

Among 1696 participants, the average age was 44.38 ± 6.10 years, and 1124 were men (66.3%). After a 45-year follow-up, a total of 201 (11.9%) stroke-related deaths occurred. After the adjustment, the COX proportional hazard model showed that among the participants with SBP ≥ 160 mmHg or DBP ≥ 100 mmHg in 1976, the risk of stroke-related death increased by 217.5% (hazard ratio [HR] = 3.175, 95% confidence interval [CI]: 2.297-4.388), and the adjusted HRs were higher in male participants. Among the participants with hypertension in 1976 and 1994, the risk of stroke-related death increased by 110.4% (HR= 2.104, 95% CI: 1.632-2.713), and the adjusted HRs of the BP changes were higher in male participants. Body mass index (BMI) significantly mediated the association of SBP and stroke-related deaths and this mediating effect was moderated by gender.

In a 45-year follow-up, high BP and persistent hypertension are associated with stroke-related death, and these associations were even more pronounced in male participants. The paths of association are mediated by BMI and moderated by gender.

Contrast-enhanced ultrasound (CEUS) can detect lesions hidden in inflammatory regions and find necrosis or areas of severe fibrosis within the lesion. This retrospective study aimed to compare the diagnostic accuracy of solid pancreatic lesions using percutaneous ultrasound (US)-guided fine-needle aspiration (FNA) with or without CEUS assessment.

Clinical, imaging, and pathologic data of 181 patients from January 2014 to December 2018 in Pecking Union Medical College Hospital, with solid pancreatic masses who underwent percutaneous US-FNA and ThinPrep cytologic test were retrospectively evaluated. Patients were divided into CEUS and US groups according to whether CEUS was performed before the biopsy. According to FNA cytology diagnoses, we combined non-diagnostic, neoplastic, and negative cases into a negative category. The positive category included malignant, suspicious, and atypical cases. The final diagnosis was confirmed by pathology or clinical and radiological follow-up for at least 12 months. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of US-FNA were evaluated between the two groups.

This study enrolled 107 male and 74 female patients (average age: 60 years). There were 58 cases in the US group and 123 cases in the CEUS group. No statistically significant differences in age, gender, or lesion size were found between the two groups. The diagnostic accuracy of the CEUS group was 95.1% (117/123), which was higher than the 86.2% (50/58) observed in the US group (P = 0.036). The sensitivity, specificity, PPV, and NPV of the CEUS group were increased by 7.5%, 16.7%, 3.4%, and 18.8%, respectively, compared with the US group. However, the differences of the two groups were not statistically significant.

Compared with the conventional US, the use of CEUS could improve the biopsy accuracy and avoid the need for a repeat biopsy, especially for some complicated FNA cases.

GALLIUM is a global phase III study that demonstrated significant improvements in progression-free survival (PFS) for obinutuzumab plus chemotherapy (G-chemo) vs. rituximab plus chemotherapy (R-chemo) in previously untreated patients with follicular lymphoma (FL). This study aimed to report the results of a subgroup of patients in China.

Patients were randomized to G-chemo or R-chemo. Responders received maintenance therapy for 2 years or until disease progression. The primary endpoint was investigator (INV)-assessed PFS. Secondary endpoints included the overall response rate (ORR) and complete response rate (CRR) at the end of induction chemotherapy, overall survival (OS), and safety.

Overall, 58 patients with FL were randomized to the G-chemo (n = 25) and R-chemo arms (n = 33). The INV-assessed PFS rate at 3 years was 81.8% in the G-chemo arm, vs. 70.2% in the R-chemo arm (hazard ratio 0.35; 95% confidence interval: 0.09-1.34; P = 0.1120). The INV-assessed CRRs (without positron emission tomography [PET]) in these arms were 24.0% and 21.2%, respectively, whereas the ORRs were 80.0% and 90.9%, respectively. INV-assessed CRR-PET was 52.6% in the G-chemo, vs. 60.9% in the R-chemo. Median OS was not reached in either arm. Grade 3 to 5 adverse events were more frequent in the R-chemo arm (97.0% vs. 88.0%).

The results of this subgroup analysis were consistent with those of the global population, and they suggest that G-chemo has a positive benefit-risk profile in patients from China with FL.

ClinicalTrials.gov, No. NCT01332968.

Massive bleeding is the main concern for the management of placenta percreta (PP). Intra-abdominal aortic balloon occlusion (IABO) is one method for pelvic devascularization, but the efficacy of IABO is uncertain. This study aims to investigate the outcomes of IABO in PP patients.

We retrospectively reviewed the clinical data of PP cases from six tertiary centers in China between January 2011 and December 2015. PP cases with/without the use of IABO were analyzed. Propensity score matching analysis was performed to reduce the effect of selection bias. Postpartum hemorrhage (PPH) and the rate of hysterectomy, as well as neonatal outcomes, were analyzed.

One hundred and thirty-two matched pairs of patients were included in the final analysis. Compared with the control group, maternal outcomes, including PPH (68.9% vs. 87.9%, χ²= 13.984, P < 0.001), hysterectomy (8.3% vs. 65.2%, χ²= 91.672, P < 0.001), and repeated surgery (1.5% vs. 12.1%, χ² = 11.686, P= 0.001) were significantly reduced in the IABO group. For neonatal outcomes, Apgar scores at 1 minute (8.67 ± 1.79 vs. 8.53 ± 1.68, t=-0.638, P= 0.947) and 5 minutes (9.43 ± 1.55 vs. 9.53 ± 1.26, t = 0.566, P = 0.293) were not significantly different between the two groups.

IABO can significantly reduce blood loss, hysterectomies, and repeated surgeries. This procedure has not shown harmful effects on neonatal outcomes.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis.

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq).

TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown- TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation.

TPCN2 might be a potential protective factor against SLE.

Previous studies have shown that bufalin exerts antitumor effects through various mechanisms. This study aimed to determine the antineoplastic mechanism of bufalin, an extract of traditional Chinese medicine toad venom, in ovarian cancer.

The 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT), 5-ethynyl-2^′-deoxyuridine (EdU), and colony formation assays were used to investigate the antiproliferative effect of bufalin on the ovarian cancer cell line SK-OV-3. Molecular docking was used to investigate the combination of bufalin and epidermal growth factor receptor (EGFR) protein. Western blotting was performed to detect the expression of EGFR protein and its downstream targets.

Bufalin inhibited the proliferation of SK-OV-3 cells in a dose- and time-dependent manner. Bufalin was confirmed to combine with EGFR protein using molecular docking and downregulate expression of EGFR. Bufalin inhibited phosphorylation of EGFR, protein kinase B (AKT), and extracellular signal-regulated kinase (ERK).

Bufalin suppresses the proliferation of ovarian cancer cells through the EGFR/AKT/ERK signaling pathway.

Appropriate management of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is very important because such exacerbation negatively impacts patients’ health status, disease progression, and mortality. Exacerbation episodes are mainly triggered by viral and bacterial infections, and one study showed that 55% of hospitalized patients with AECOPD had a bacterial infection.^[1]Some analyses have suggested that antibiotic therapy can reduce the risk of short-term mortality and improve the prognosis. However, not all patients with AECOPD benefit from antibiotic therapy. The blood eosinophil count has been used as a biomarker for eosinophil-associated airway inflammation and sepsis. However, the association between the peripheral blood eosinophil count and bacterial pathogens has not been reported. Our aim was to analyze the associations among the eosinophil count, bacterial pathogens, clinical treatments, and prognosis of patients and provide useful and comprehensive references for AECOPD management.

Immunoglobin (Ig) G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition characterized by elevated serum IgG4 levels and multi-organ involvement. The characteristic histological findings of IgG4-RD are dense lymphoplasmacytic infiltration, fibrosis, and massive IgG4 positive plasma cells infiltrating the affected tissues.^[1]Previous studies have demonstrated various relapse predictors corresponding to demographic, clinical characteristics, laboratory test results, and treatment agents. However, no study has revealed the risk factors of flares in pathology. This study aimed to ascertain whether the pathological characteristics are related to therapeutic outcomes.

Far lateral approach (FLA), together with its modified approaches, is a fundamental surgical approach for surgical resection of lesions located at the ventral or ventrolateral side of the foramen magnum.^[1,2,3,4,5]The key procedure in FLA is exposing the vertebral artery (VA) especially the V3 segment.^[1,5,6]When performing an FLA, most neurosurgeons choose to expose the suboccipital triangle (formed by the rectus capitis posterior major, the superior oblique, and the inferior oblique) as a key anatomical landmark initially and then expose the V3 segment.^[1,2,5,6,7]However, on the one hand, this muscular anatomical landmarks-suboccipital triangle varies in depth, morphology, and location in different patients, which increases the risk of VA injury during surgery.^[3]On the other hand, this procedure could lead to exposing difficulty due to the obstruction of overlying layers of muscles and the distribution of blood vessels, which could prolong the time for craniotomy fairly. The course of VA could vary, such as looping backward and bulge posteriorly between the lips of the suboccipital triangle, where it could be damaged if one expects it to be found in the depth of the suboccipital triangle.^[3]Thus, neurosurgeons have the potential for VA injury and a rather prolonged time to successfully expose VA.

To the Editor:Rheumatoid arthritis (RA) is a chronic autoimmune disorder not only characterized by joint symptoms but also extra-articular and systemic manifestations.^[1]Traditionally, the evaluations of RA had centered on laboratory measures of inflammation and clinician-generated assessments. However, patientreported outcomes (PROs) are recommended by several guidelines to assess disease progression. PROs also can contribute to reduce discrepancies between physicians’ evaluation and patients’ own judgment on disease status and their importance on disease management and physician-patient communication has been identified during the past decennia.^[2]However, it is uncertain whether the awareness has promoted the usage and reporting of PRO measures in RA-related research and clinical practice in Chinese population. Thus, this study systematically reviewed the PRO measures collected in recent researches and summarized the PRO results among Chinese RA population.

To the Editor: Osteoarthritis (OA) is a disease associated with high morbidity and disability. Obesity, typically measured as a body mass index (BMI) ≥30 kg/m², is a well-known risk factor for the onset of OA and its related complications.^[1]Interestingly, these two diseases may have common underlying mechanisms which contribute to the pathogenesis, such as genetic changes, and these mechanisms have not yet been fully explored. Gene expression profiling is a powerful tool used to systematically identify the molecular features underlying genetic variations associated with complex multifactorial diseases such as OA. In addition, it has been shown the significance of gene expression in understanding the mechanisms in the pathogenesis of obesity and OA.^[2]This study hypothesized that hub genes could explain the relationship between obesity and OA. Consequently, identifying that these genes are involved could provide insights into the detailed regulatory mechanisms of obesity on OA.

To the Editor:The SRY-related high-mobility-group-box protein-2 (SOX2) is most notably expressed in the eye, placodes, forebrain, and hypothalamus-pituitary and is involved in early embryonic development.^[1]Loss-of-function mutations or deletions inSOX2could lead to uni- or bi-lateral anophthalmia/microphthalmia (A/M) as well as other related disorders, such as anophthalmia/esophageal-genital syndrome. An increasing number of studies have found thatSOX2mutations can cause variable extraocular symptoms, including growth retardation, sensorineural hearing loss, mental retardation, no pubertal signs, and male genitourinary tract malformations (micropenis, cryptorchidism, and hypospadias). Indeed, cases withSOX2pathogenic mutations but no or minor ocular symptoms have been reported less frequently. Several studies found thatSOX2heterozygous mutations cause typical signs of complete hypogonadism without major ocular malformations in men or women, such as isolated hypogonadotropic hypogonadism (HH), but no other HH pathogenic gene was identified.^[2,3]Therefore, our study is the first to report the cases of three Chinese patients withSOX2mutations referred due to micropenis and/or cryptorchidism combined with craniofacial deformities or intellectual disability.

To the Editor:Contact heat evoked potentials (CHEPs) has become an important electrophysiologic diagnostic approach for small fiber neuropathy,^[1]which is characterized by involvement of myelinated Aδ and unmyelinated C fibers as a result of various etiologies.^[1,2]CHEPs are affected by gender, age, body height, and so on.^[1,2]The effect of the second to fourth (2D:4D) digit ratio on CHEP parameters has not been investigated. Digit ratio is defined as the length of the index finger dividing the length of the ring finger, which is smaller in men than in women.^[3]We aimed to find out whether digit ratio has any role influencing CHEPs, and to strengthen the understanding and improve the methodology of CHEPs.

To the Editor: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancer types and places a heavy burden on human health. The early diagnosis and prognosis monitoring of ESCC is important for therapy. Despite recent progress in treatment regimens for ESCC, the prognosis of ESCC remains poor.^[1]Therefore, it is important to find new molecular therapeutic targets and prognostic monitoring biomarkers for ESCC patients. In this study, we aimed to explore new prognostic biomarkers for ESCC.

To the Editor:Esophageal atresia (EA) is the most common congenital abnormality of the esophagus. In 70% to 90% of those born with EA, a tracheoesophageal fistula (TEF) co-occurs. Since Vogt^[1]recognized and classified the types of anomalies in 1929, many other classification systems have been proposed, including the Ladd, Gross, Swenson, and Kluth classification systems.^[2]However, the Gross classification of anatomical patterns of EA/TEF proposed in 1953 is one of the most widely accepted and used classification systems^[3]and has been cited inPediatric Surgery.^[4]While surgical and imaging techniques have evolved considerably over recent decades, 434 consecutive cases of EA/TEF in China were reviewed. Through closely examining the imaging studies and the pathoanatomical configurations of these patients, we identified certain "defects" and details in the illustrations that need modification.

To the Editor:The kidney is a highly energy-consuming organ and is prone to damage if there is an energy supply disorder. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a serine/threonine kinase that plays a critical role in metabolism, autophagy, inflammation, and mitochondrial homeostasis. AMPK is involved as an energy sensor in the physiological and pathological processes of the kidney.

To the Editor: Diverticular disease is common worldwide and the incidence of this disease increases with aging. Complicated diverticulitis is serious and includes abscess, fistula, obstruction, and peritonitis. Eventually, surgical treatment is recommended to the patients with symptomatic complications. Among these, colocolic fistula caused by diverticulitis is rare findings and especially, sigmoid-sigmoid fistula is an extremely rare complication. The present report describes a case of sigmoid-sigmoid colon fistula caused by diverticulitis. The results of this case may help physicians to recognize that multidisciplinary management and surgery are needed for the treatment of complicated diverticulitis with fistula.

To the Editor: Total aortic arch replacement (TAR) is a surgical procedure associated with significant perioperative risks, leading to a higher rate of mortality and neurologic complications. Ascending aortic or hemiarch replacement is associated with less complicated procedures, which can be used to effectively resect the proximal intimal tear and potentially improve the survival rates in these patients.^[1]Hybrid aortic repair, combining openchest surgery and stent placement has been effectively used in patients with an aortic arch aneurysm.^[2]Although a hybrid technique is often followed, only a limited number of studies with a small number of cases have investigated the application of this procedure for the treatment of type I aortic dissection.^[1,2]This study aimed to evaluate the early and mid-term safety and efficacy of the hybrid technique in this cohort by analyzing a large sample size.

To the Editor: As of August 9, 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 19,432,244 people and caused 721,594 deaths globally. To timely identify the infected persons, nucleic acid detection screenings have been carried out for high-infection risk groups in areas known to have coronavirus disease 19 (COVID-19) cases, such as Wuhan, Beijing, and Xinjiang. The rapid identification of infected patients and the implementation of quarantine measures play an important role in preventing the transmission of SARS-CoV-2. However, there are some issues associated with large-scale screening for this virus. The consumption of equipment and reagents for specimen collection and detection is high, resulting in elevated screening costs. Moreover, with the increase in the number of samples collected, the testing capabilities of medical institutions have reached a saturation point, hindering the speed and scope of large-scale screenings. For this reason, the mixed detection after RNA extraction (detection in a mixture of nucleic acids extracted from several patients) or before RNA extraction (detection in a mixture of pharyngeal swab transfer buffer obtained from different patients before nucleic acid extraction) has been proposed in many regions.^[1]However, both the pooling of swab transfer buffer before nucleic acid extraction and pooling of RNA after nucleic acid extraction inevitably cause dilution of samples and decrease of detection sensitivity. However, there is still a lack of research on how to effectively improve the screening efficiency and control the decrease of sensitivity caused by dilution in an appropriate range. In this study, we designed a novel 10-in-1 test (ten pharyngeal swab samples from ten individuals were placed in one custom-made virus collection tube [CMT] for nucleic acid extraction and testing) by optimizing the current mixed acquisition technique, and after a promising pilot test.