Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

Neoadjuvant chemotherapy increases the 5-year overall survival of patients with resectable cervical cancer: A systematic review and meta-analysis

Cervical cancer is a global health challenge in women. Neoadjuvant chemotherapy (NACT) is a recent prospect for alternative cervical cancer treatments. This study investigated the efficacy of NACT against resectable cervical cancer based on the medium and long-term survival of patients with the disease. We searched through PubMed, Web of Science, EBSCO and Cochrane Library for relevant reports published by June 2020. The primary outcomes were 3-year and 5-year progression-free survival (PFS) and overall survival (OS) of patients with resectable cervical cancer. Overall, 22 publications encompassing 5627 patients fulfilled the inclusion criteria. We found NACT not to affect both 3-year PFS and OS as well as 5-year PFS of patients with resectable cervical cancer. However, NACT significantly improves the 5-year OS of patients with resectable cervical cancer (HR = 0.83, 95% CI: 0.73–0.94, p = 0.013). Subgroup analysis (RCTs, non-RCTs, NACT + surgery + AT vs. surgery + AT, NACT + surgery + AT vs. CCRT/RT/CRT) further revealed NACT had no significant effect on 5-year PFS of patients with resectable cervical cancer, converse to the 5-year OS subgroup analysis, which validated the beneficial effect of NACT in patients with resectable cervical cancer. In addition, the effect of NACT was most significant in the non-RCTs subgroup (p = 0.012). NACT may improve the long-term prognosis of patients with resectable cervical cancer. However, further large-scale multicenter studies are needed to validate this finding.     

Impaired Sensorimotor Gating Using the Acoustic Prepulse Inhibition Paradigm in Individuals at a Clinical High Risk for Psychosis

Many robust studies have investigated prepulse inhibition (PPI) in patients with schizophrenia. Recent evidence indicates that PPI may help identify individuals who are at clinical high risk for psychosis (CHR). Selective attention to prepulse stimulus can specifically enhance PPI in healthy subjects; however, this enhancement effect is not observed in patients with schizophrenia. Modified PPI measurement with selective attentional modulation using perceived spatial separation (PSS) condition may be a more robust and sensitive index of PPI impairment in CHR individuals. The current study investigated an improved PSSPPI condition in CHR individuals compared with patients with first-episode schizophrenia (FES) and healthy controls (HC) and evaluated the accuracy of PPI in predicting CHR from HC. We included 53 FESs, 55 CHR individuals, and 53 HCs. CHRs were rated on the Structured Interview for Prodromal Syndromes. The measures of perceived spatial co-location PPI (PSCPPI) and PSSPPI conditions were applied using 60- and 120-ms lead intervals. Compared with HC, the CHR group had lower PSSPPI level (Inter-stimulus interval [ISI] = 60 ms, P < .001; ISI = 120 ms, P < .001). PSSPPI showed an effect size (ES) between CHR and HC (ISI = 60 ms, Cohen’s d = 0.91; ISI = 120 ms, Cohen’s d = 0.98); on PSSPPI using 60-ms lead interval, ES grade increased from CHR to FES. The area under the receiver operating characteristic curve for PSSPPI was greater than that for PSCPPI. CHR individuals showed a PSSPPI deficit similar to FES, with greater ES and sensitivity. PSSPPI appears a promising objective approach for preliminary identification of CHR individuals.     

Metastasis of oral squamous cell carcinoma to the parotid lymph nodes

Parotid lymph node (PLN) metastasis greatly worsens the prognosis of patients with oral squamous cell carcinoma (OSCC) and poses a great challenge for further treatment of OSCC. The clinicopathological characteristics and treatment strategies for PLN metastasis from OSCC need to be comprehensively elucidated. A retrospective review of OSCC patients who experienced postoperative PLN metastasis in our department between 2000 and 2018 was performed in this study. A total of 47 OSCC patients with postoperative PLN metastasis were identified. PLN with metastasis were divided into three groups based on the location: parotid tail (PLN-t), superficial lobe (PLN-sl), and deep lobe (PLN-dl). Most of the patients experienced PLN metastasis within less than 12 months after the primary surgery for OSCC. Comparatively, patients with PLN-sl metastasis were more prone to have infiltration of the facial nerve. The tongue and buccal mucosa were the most frequent primary sites associated with PLN metastasis from OSCC. PLNs in the parotid tail were most commonly affected by the metastasized OSCC. Consequently, we recommend a series of strategies for the prevention and treatment of PLN metastasis for OSCC patients. In conclusion, PLNs should not be overlooked during preoperative evaluation and postoperative follow-up examinations for OSCC patients.     

Thinned-out skin paddle versus collagen matrix as an optimized peri-implant soft tissue following fibula osteoseptocutaneous free flap: 3-year retrospective study

The objective of this study was to compare the implant longevity following two methods of peri-implant soft tissue optimization following free fibula flap (FFF): thinning of skin paddle (SP) and collagen matrix (CM). All patients who underwent rehabilitation with dental implants after mandibular reconstruction with FFF between June 2009 to May 2014 were retrospectively reviewed. Two methods of peri-implant soft tissue optimization were applied: (1) SP group, (2) CM group. Outcome measurements were: modified plaque index (mPI), modified sulcus bleeding index (mSBI), probing depth (PD), marginal bone loss (MBL), implant success rate and complication rates. A total of 24 patients with 69 implants were included in the study, with 8.7% (n = 6) of implants lost in 3 years. No statistically significant difference was found regarding the outcome measurements in both groups. Failed implants presented with statistically significant higher mPI, mSBI, PD and MBL scores during prosthesis delivery and subsequent follow-ups (P<0.03). In the SP group, one patient experienced SP necrosis which later underwent soft tissue optimization using CM. CM is an alternative peri-implant soft tissue, while thinning of SP is feasible if thickness is well controlled.     

苦寒药与生物钟基因的关系研究进展＊

苦寒类中药善于清热燥湿以改善机体内环境稳态，目前在临床上被广泛应用于糖尿病、肥胖、炎症、菌群失调等慢性或代谢性疾病，而这些疾病往往都伴随着机体生物钟系统的失衡。改善生物钟失衡可能是苦寒药治疗这些疾病的作用机制之一，同时，在生物钟的调控下，机体新陈代谢及内分泌等行为的节律性波动也可能影响苦寒药的药效。既往对苦寒药在临床应用上的研究大部分集中于胃肠动力及激素等基础研究上，从生物钟基因的角度鲜有见到深入的研究与阐述。因此，本文从临床常用苦寒药对生物钟基因的影响及生物钟基因对苦寒药作用的影响两个方面探讨苦寒药的应用，同时分析二者之间的关系和归纳苦寒药影响生物钟基因共同的物质基础，以期为苦寒药作用多靶点以及指导临床合理用药和中药药性物质基础研究提供参考。